Great. Thank you very much everyone for attending. I am Max Skor, a Biotech Analyst with Morgan Stanley. Before we get started, for important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. With that, I am very happy to have the Pharvaris team with me today. Berndt Modig, CEO, and Maggie Beller, Head of IR. Thank you very much for joining us. Thank you, Max. Good to be here. Great. Maybe we start off, I think this is the third year in a row you have attended. We have sat here at the fireside chat. This is a momentous time in the story of Pharvaris. If you can just maybe step back and give us a brief overview of just how you got here and what are the key steps going forward? Sure. Actually, our journey, or my personal journey in HAE started 23 years ago, not with Pharvaris, but with the company that developed icatibant. I worked there together with Jochen Knolle, who is the inventor of icatibant. Then in, as we all know, Shire took over in 2008, and it then became, and still is, the most widely used acute therapy for subcutaneous injection. But already back then, we knew that patients were looking for better treatments and already then we were just starting to think about the vision for an oral therapy. Then a couple of years later in 2015, starting operations in 2016, Jochen and I started Pharvaris, with the idea to develop an orally available B2 receptor antagonist, really from chemistry square one, really from scratch. We are really excited to what we see today with what came out of that, is deucrictibant. The properties of that molecule makes it very different from icatibant, that it is a B2 receptor antagonist, but it is, to our knowledge, the first and only orally available B2 receptor antagonist. It also has the properties that make it half-life and so on, that makes it suitable for prophylactic development, unlike icatibant. Looking at the therapeutic area for over more than two decades, you see the big unmet need for an efficacious oral therapy option, and that there is still nothing approved out there. We are of course hoping that deucrictibant is going to be the first orally available B2 receptor antagonist, an oral therapy with a high level of efficacy for people living with HAE. Great. Thank you very much for that introduction. When we think about the HAE market, we have the on-demand market, which you also have a formulation for of deucrictibant, and then the prophylactic. Let us start with the prophylactic because you just reported impressive phase III CHAPTER-3 data. Maybe give us a high-level overview of the overall efficacy profile, and then we can dive into specifics. Yeah. You saw the data. We had a remarkable 87% efficacy in the type 1, type 2 population of hereditary angioedema. The study included as also part of the overall protocol, patients with normal C1 mutations, other mutations. The primary endpoint included a small number of such patients and that total primary endpoint and efficacy attack reduction was 83%. That really means that we are in the area of what we can call injectable-like efficacy. If you look at the other injectables in the prophylactic space therapies out there all seems to be almost like a ceiling. I was thinking more or less, maybe not coincidence, but there seems to be like there is a maximum level of efficacy at around 87%. We are very happy to see that with deucrictibant, and it really puts us in a very differentiated position vis-à-vis the others. As I said, we see a huge unmet need for an oral therapy that really provides that level of efficacy. Maybe if we can dive into the key secondary endpoints, maybe you can talk about the baseline characteristics and how that compares to competitors in the space. Specifically, I imagine everyone's looking at ORLADEYO, and how that phase III lined up versus CHAPTER-3. Yeah, the baseline characteristics are very similar to other therapies. In terms of attack frequency, they range from, I think the lowest is the TAKHZYRO with 1.7, and the highest is ORLADEYO indeed. We were sort of in the little over 2.1, I think it was in our case. It's all very similar. These are fairly severe patients. Yeah. I think that's very comparable. I'll add on that those were our placebo rates in the full 24-week study. For the baseline characteristics leading into the study, our average attack rate was about 3.6, so that is a more severe patient population. We were incredibly impressed to see the 87% attack reduction given the severity of the patients that we were treating. I guess after the results came out, there were some questions around the safety profile. We actually hosted a KOL a couple of days later. The KOL was comfortable with the enzyme elevations given the compounding or confounding factors such as androgen exposure, fatty liver. Could you comment on those? Yes, happy to. In our study, we did see two Grade 3, Level 2 liver enzyme elevations. As you mentioned, Max, one of those patients did have fatty liver disease. That was also a normal C1 patient. That person ended up discontinuing the study drug but stayed on the study, so we were able to continue their lab assessments. The second patient had previously used androgens. They actually stayed on study and completed the study and then rolled over onto the open label extension. Both of those patients neither were symptomatic and neither saw elevated bilirubin, so we were pleased to see that. Okay. That's very helpful. There was one patient, I believe, laryngeal attack. Any commentary around that? Absolutely. That was our Grade 4 finding, which is the same as the serious adverse event in the safety table. This was, once again, a person with normal C1. They had a plasminogen mutation. This person, unfortunately, leading into the study, had experienced severe laryngeal attacks, as many as 19 laryngeal attacks in the three months leading up to the study. These attacks required constant intubation, so this was somebody who had been intubated multiple times. Upon start of the study, this person experienced a 90% decrease in their attack frequency, so really impressive efficacy findings there. At one point, they had a laryngeal dyskinesia, which just means that they had difficulty breathing, that resulted in them being hospitalized and being intubated. While intubated, they were scoped, and it was confirmed that there was no angioedema associated, so this was not a laryngeal attack. It was just a result of the frequent intubation prior to the study start. This person stayed on study drug. They completed the study. In fact, afterwards, we reached out to the PI just to see how the person was feeling. They had reported that they were happy with their deucrictibant treatment and actually were able to go back to work. Not only did they experience the improved efficacy but also improved quality of life. We view that as a real success story with deucrictibant. That's great. Yeah, maybe I should also add to that. It's hard to imagine for any of us here what it's like to have 19 laryngeal attacks and suffer through that. This is, as Maggie said, is a normal C1 patient, and part of our approach here and also as we designed the study was to include, as I mentioned, normal C1 patients. This is not an insignificant portion of the patient population. Also to remind everybody, because of the mechanism of B2 receptor antagonist, that is really the only mechanism that has real efficacy for this patient population. Can you talk about that opportunity? Yes. It's estimated now that approximately 20% of the HAE population is the normal C1 mutations. That follows a different pathway. It doesn't go through the kallikrein pathway, so it's already at the bottom of a B2 receptor level. Then you can really most effectively treat that condition. They do get therapy today with the existing therapies, but that is because the more generalized label for those indication, hereditary angioedema, because the normal C1 is also sometimes called type 3. It's one form of hereditary angioedema. But with our data now, we hope to get that also included in our label and also to finally have a real efficacious therapy for these type of patients. Are these patients generally managed with on-demand or prophylactic treatment? I think for the most part, it's on-demand today. Many use icatibant. They also use stride and the other drugs. They do get the other drugs, also prophylactic and prescribed, but with modest efficacy or very low efficacy. Then maybe just going back to the safety profile, how does it compare to ORLADEYO? I think on the ORLADEYO label, something's called out at higher doses, cardiac implications. Any commentary around how deucrictibant compares to that? Yeah. Thanks for the question. That is something that we're really proud of. We didn't see any additional cardiovascular signs, and in fact, we saw one of the major pushbacks that we get for the other approved oral is GI side effects. We did not see an increase in GI risk with deucrictibant treatment, and the placebo and deucrictibant arms were balanced with respect to GI as well. Not only do we have a thorough QT waiver, we put out a lot of cardio safety data, and we were happy to see in clinical studies that there's no additional cardio risk with deucrictibant. Okay. Now going down the path of potential approval in prophylactic. We'll touch on on-demand in a bit, but what have you learned from the ORLADEYO experience so far? How are you going to approach marketing, talking to physicians? How should we think about the launch curve? Yeah. So on the ORLADEYO, as we know, had pretty strong uptake, which is not a surprise to us because it reflects the fundamental unmet need for an oral therapy. So patients desire to get away from injections. I think what we've seen now since the launch of ORLADEYO is that there's a very high churn rate. There's very many patients drop off after trying it. I think also in the call that you mentioned them, KOL mentioned that you also wrote about this, said that 50% of his patients discontinued ORLADEYO within six months. That is then go back to the injectables, and that's really simply because of the lower efficacy. So that patient segment of patients who have tried ORLADEYO, and the reason for trying it is, of course, the desire for an oral, and they go back to the injectables because it didn't do so well for them. With deucrictibant now, they have the opportunity then to try again. So I think that the propensity for that type of patient to try deucrictibant would be very high. So that's a very clear segment. We estimated some numbers, I think Christa has also mentioned numbers ranging from up to 1,900 patients that have tried ORLADEYO and dropped off. So that's very clear. Then there is the patient population that, of course, are aware of that. They're still waiting for an oral, but they don't want to take that risk of starting to having attacks again, so they stay on the injectable, and they're waiting for deucrictibant, you can say. So that's another segment that's very logical for us to approach. Then the first-line population, newly diagnosed, it's very logical to start with an oral as a first-line therapy. And there are 150 - 250 patients every year that come into the mix, and that kind of accumulates over time. And what we hope to see, of course, is that when somebody starts with deucrictibant, that they would be satisfied and then the search is over, and there's no need to switch. So then with that building patient population, also from the new patients, it kind of accumulates over time. And Chief Commercial Officers like to describe it as a pancake effect, that it is basically accumulation of patients coming in and newly diagnosed. So maybe that leads into the on-demand opportunity, but stepping back and thinking about the prophylactic versus on-demand, having dual formulations of the same drug, how are you thinking about the market opportunities for each? Then on-demand launching first, how does that help you define the prophylactic market going forward? Yeah. We do think that the on-demand market is a viable market. Also in the future, there are certain patients that prefer to treat when the attack happens, especially if you have something that's very reliable and simple. Again, also in the on-demand segment, same phenomenon. There is an oral therapy, but with not the optimal efficacy. So I think similar to the prophylactic setting, we hope and expect that deucrictibant will also take over a lot of those patients. Also, there are patient populations still on the icatibant, and I think that's 65% or something, more actually, patients that really are still on the icatibant. What they like about icatibant is the reliability, efficacy, and they trusted in the mechanism. But if you have an oral that works as good or even potentially better, then that's a very logical switch for that patient population as well. So it's a very similar dynamics. I think there is a segment of people living with HAE that may want to stay on demands. We think that's also why we're happy that we have both options for the patients. In regards to the actual segment breakdown, do you see prophylactic growing or on-demand growing? How does that look? The different growth factors. Overall, the prophylactic segment continues to grow. I think that you've seen that is clearly the trend. I think that's also in the treatment guidelines that patients really should be on prophylaxis and not to have attacks. So I think that's clearly the trend. I think we've seen that over the years, and I think that continues. But as I said, I think there's still a remaining segment where the on-demand therapy option also could make sense. I think also patients that are able to maybe switch back and forth are also very relevant. Yes. Based on our conversations with KOLs, it sounds like all prophylactic patients also have an on-demand that they carry with them for breakthrough attacks. How does having two formulations of the same drug potentially address that issue? Yeah. The first two, I think we can describe as potential combo use, and I think that the treatment modalities in HAE or in angioedema is really exposure driven, so it's all about maintaining a certain therapeutic exposure. Unlike some other diseases where you have to approach it from a different side. A breakthrough attack typically occurs when that exposure and the efficacy is not there, so you're basically topping up with the same drug. Combo use from a medical perspective or from mechanistically is fine, and we've seen that as also a potential for deucrictibant. Okay. I'll also add that right now in clinical practice, people use the same mechanism to rescue their attacks when they have breakthrough attacks. Right now, if you're on TAKHZYRO or ORLADEYO, which are kallikrein inhibitors, and you have a breakthrough attack, you treat with Ekterly, which is also a kallikrein inhibitor. That is a well-understood additive process. For us, we're using that same philosophy of mechanism plus mechanism. Do you have any? I am going to ask you to put some numbers or percentages around that based on what we have learned from the Ekterly launch or what you have learned from talking to KOLs. I think right now we are seeing that people on ORLADEYO tend to have about 6-1 2 breakthrough attacks a year. So those are treated in a number of different fashions. Many of them are with Ekterly. For TAKHZYRO, we are seeing that although you see in the clinic there is 87% attack reduction as people have been moving from the two-week treatment regimen to the four-week treatment regimen, there may be more breakthrough attacks there. We have not seen exact numbers around how many Ekterly-treated attacks are prophylactic breakthroughs versus individual patients who are just treating attacks as they happen and are not on background prophylaxis. Okay. Maybe we can pivot over to the on-demand opportunity here. You have a PDUFA date coming up. Maybe just stepping back, give us a quick overview of the efforts that you have already accomplished and what is still ahead. Yeah. The launch preparations are full underway and fully on track, and the team is growing. There is a tremendous growth in the organization, a lot of people coming on board on the building the commercial team. We are also very happy that there is good talents that people who have had prior experience with HAE and come from companies, and have other therapies in HAE and have worked on those therapies, or head of patient services who had launched Firazyr, for example. I think it is almost 40%, a little bit more, of our team members building from the top down have prior experience in the area. So that is very strong. Also, there is a lot of excitement about Pharvaris. So also from other skilled talent from other rare disease companies joining us. So that is going really well and fully on track. Then with getting closer to the remaining phase in building the sales force and then to get ready for the launch. How should we think about the sales force? Yeah. It's relatively compact compared to many other therapeutic areas. I think that what we are building is very similar to what others have as well. I mean, to have 35 people in the field and then the overall commercial organization, I think it's going to be around 70. Then adding a few more, maybe total of about 90 people by the time we launch prophy. HAE is an area that's also suitable for a smaller company like us to commercialize on their own and achieve forward integration and to continue to build. In regards leading up to the April 2027 PDUFA date, what interactions do you expect to have with regulators? How is everything going, getting commercial supply up and running? Then we can potentially talk about expected label, price, economics. Yeah. The review is ongoing, and then there will be coming soon also some mid-review meetings. That's underway. We also, on the CMC and drug supply, that's also getting ready for the launch and also on track. Then on pricing, that's something we're evaluating now. I think that fundamentally, we'll be looking to price for value. I think that what we also seen in other launches in HAE, there haven't been any disruptive pricing strategies by anyone. I think with the profile of deucrictibant, I think we have the potential to really illustrate that value that can provide an attractive pricing. I think a key point also in on-demand is, and our data in on-demand is significantly differentiated when it comes to single-dose attack resolution, which is a very important aspect clinically and also in real life for patients trusting that what they take is going to help them, and they don't have to worry about, should I take a second dose or not? To get the complete symptom resolution, I think that's a clear differentiator versus Ekterly. Then another point is also the endpoint and data point that we have in our protocol, which is at the beginning of the whole attacks process, is the so-called end of progression. That is also a clinically meaningful endpoint, and so subject to agreement with the regulators, we may be able to get that into the label as well. The end of progression means that this is when a patient really feels that things are under control. It's not going to get worse. We see that in 17 minutes with deucrictibant. I'll highlight that we had 12 endpoints in our study, all of which hit statistical significance in a hierarchical fashion. Not sure we're going to be able to get all 12 into the label. That would be a very large packet insert, but as Berndt highlighted, the key differentiating factors are the rapid onset of action, the complete symptom resolution, and the single-dose durability. If we're able to have a label that's appropriately demonstrating those three factors, I think our commercial team will have a successful launch. Okay. Since we have an oral and on-demand, we have an oral and prophylactic. Specifically in on-demand, how should we think about the launch curve? I imagine people are going to immediately comp it to Ekterly in early stages. How are you thinking about that? Yeah. I think the level of awareness in the community that deucrictibant is coming is very high. That speaks in our favor. I think also part of our strategy is also to the extent within compliance guardrails, to identify patients that could be interested in deucrictibant on-demand on the launch. We have this so-called opt-in program, where patients consent to receive information. We are already, I think, up to almost 2,000 patients, targeting almost 3,000 patients by the time we get to launch. I think that puts us in a strong position, and that kind of accelerates further then as we then progress further to the prophylactic launch, because then we already have a good patient population as a basis that could potentially also then migrate over to the prophylactic version of deucrictibant when it comes. I think that gives us a very unique advantage in the real high-value launch, which is the prophylactic, as a new market entrant, because we have this sort of stepping stone with the on-demand launch. It's all very integrated in our strategy. In regards to the opportunity in Europe, how are you sequencing the potential launches? I believe the European package is under review now. Any commentary around that? Yeah. That is under evaluation. I think that there are also other factors that play a role in the assessment of the European opportunity. Fundamentally, we would like to see deucrictibant serve the patient needs on the global scale. I think that many patients participated in our trials globally, and we would like to see what we need to do whatever we can do to achieve that. I think ex-U.S. has its own different challenges. I think also especially in HAE, the commercial opportunities, the kind of difference between the U.S. market and the rest of the world is, for most therapies, pretty significant. But in HAE, it is even more so because of the pricing structure for historical reasons, and because a lot of the first therapies in HAE started in Europe. That is something we are evaluating and more to come on that. But I think it is fair to say that there are definitely opportunities there and also not only in Europe, in Japan and potentially even China and other territories also have significant patient populations. Should we start thinking about contributions coming ex-U.S. in 2027 or 2028? How should we think about that? That is a little bit too early to guide on. We will provide more guidance on that once we have clearer visibility. Is there a U.S. expanded access program? Any color on that and how that's going? Yeah. That's in the sort of the medical area. That's something that we set up, and there's a lot of interest for that. So that's also underway. Are you getting any feedback from physicians? I imagine this is a good example for physicians who maybe weren't involved in the clinical trials to get some experience with the deucrictibant. Yeah. That's sort of still early stages there to really get some meaningful feedback there. But as I said, the program has a lot of interest, and we're really happy about that, to be able to provide that. Okay. We're careful on giving guidance around that because it could be considered pre-approval promotion since it's a medically driven program. We'll say that, as Berndt said, we obviously opened it based off of interest that we received from physicians and KOLs. All of that is reactive in response to access challenges that people have. So that does give people the ability to treat their on-demand attacks with deucrictibant prior to us getting a formal approval, but it's a medically driven program. Okay. And then maybe we have about six minutes left. Let's touch on, you have another clinical trial, CREAATE, currently ongoing. How is that going? When can we expect data, and what does that opportunity look like? Yeah. So the CREAATE trial, just to remind, that is for an indication called acquired angioedema. So that is another form of angioedema that's due to underlying disease, so basically causes C1 deficiency with the same angioedema symptoms that you see in hereditary angioedema. So basically follows the same pathway. That's about 10% of the patient population right now. There's nothing approved for that, and in our discussions with the FDA, we have received encouragement to pursue that patient population. And we see the potential for underdiagnosed situation there because, as I said, it's because of underlying disease, and these are patients that are referred by the other treating physicians when they're able to figure out what's going on with these attacks that these patients have. So with the potential then, with an approval in that indication, then that could uncover the broader opportunity. Our plan with that trial, which is ongoing and also on track, and we guided the top-line readout in Q1 next year. Our plan is then to combine the data of that study with the NDA filing for prophy. With that, we then may have a potential upside subject to regulatory agreement and concurrence for priority review, but that remains to be seen. The fundamental goal is to, with that data together with the other data, to get the broad label for bradykinin-mediated angioedema, not just type HAE type 1 and type 2 and type 3. That would be differentiated from any offering? That's another way of differentiating. It's going to benefits prescribers. It makes their life easier, going to benefit from the payer side. So basically have a therapy that cover all forms of angioedema. There's no other company that really has that different approach. Okay. Two more questions. First, cash runway. Can you talk about your financials? Yeah. The guidance on cash is mid-2028. That relates to what we refer to as the base case and the key core focus of the company, which is to launch deucrictibant in the U.S., both in Prophy and on-demand. We are now, of course, looking at the different points of potential other capital raises, and we haven't made any decisions there yet. We've taken an opportunistic view when it comes to the potential equity. We also have other forms of financings available to us as we get closer to the commercial profile. With the financing that we did a couple of months ago, that gave us that financial flexibility. So we have a lot of options how to take the next step in our capital formation strategy, too. Okay. Then maybe in the last two minutes, over the next 6- 12 months, what are we going to hear from Pharvaris outside of potential approval, launch expectations? Should we expect more data? We talked about the CREAATE study, longer-term data, LOE, et cetera. Yeah. We plan to submit a late breaker abstract for the college meeting. That's ACAAI. That's in the first week of November, where that will be our first opportunity to present our CHAPTER-3 data to the medical community. So we're excited about that. Our manuscript is shelled out and has data starting to be dropped in it right now. We hope to publish that for CHAPTER-3 in the first quarter of next year. Also, as Berndt mentioned, as part of our NDA package, we'll be cutting our open label extension data. So when that data cut occurs, we'll either be including that as a poster or a manuscript. So we'll decide on how we're going to disclose that open label extension data. Berndt spoke about CREAATE Part 1 data. We have, hopefully, an approval with a PDUFA target date of April 23rd, and then, of course, any sort of feedback that we get from the FDA regarding our NDA submission for prophylaxis. Okay. Mid-cycle for the on-demand, should we expect an update around that? Yeah. We're probably not going to give incremental updates on our ongoing interactions with regulators, but as we've disclosed, conversations are happening, questions are being addressed. Things are going along as planned. Okay, great. Well, it sounds like everything's on track and thank you very much for attending today. Really appreciate it. Yeah. Thanks, Max. Great to be here. Thanks, Max. Thank you.