Good morning, everybody. Welcome to day one of the Citizens Life Sciences Conference. My name is Jon Wolleben, analyst here. We're pleased to have Pharvaris joining us, Berndt Modig, CEO, and Maggie Beller, head of IR, to tell us a little bit more about the story. They're operating in a really fun, exciting therapeutic area, hereditary angioedema, and a very differentiated value proposition for patients. Thanks guys for joining us, and I think Berndt, maybe to start, can you just tell us a little bit about the history of Pharvaris and what you guys are working on? Yeah. Yeah, sure thing. Thanks. Good to be here, and thanks. Also, like to point out I'm making forward-looking statements, and this also refers to our SEC filings, including the risk factors. Pharvaris, we started the business 10 years ago, and then it was based on an idea to identify the large unmet need in HAE, people living with HAE. Even today, there is still unmet need in this space. What makes Pharvaris special is that, not only that we have a product for prophylaxis and on-demand, it's also with icatibant. It's also looking broader in the form of bradykinin-mediated angioedema to look at helping people living with other forms of angioedema, not just type I and type II. That we have a mechanistic advantage there for in the sense that, acting at the end of the cascade, that we can potentially address any form of angioedema regardless of the pathway of bradykinin inhibition. The vision is to have therapy option that covers all forms of bradykinin-mediated angioedema. That's also part of our regulatory strategy, and we're also running a trial now in acquired angioedema. Mm-hmm. To be the differentiated provider of therapy options for people living with angioedema, that's our immediate vision. Of course, beyond that, as a small biotech company, we also start to think about obviously what is next and what's next in the pipeline. We also are looking at some other ideas for potentially other forms of bradykinin-mediated diseases. There's a lot to do out there. Yeah, 'cause you guys have some really compelling data, but I wanna take a step back. HAE has been, like, a fantastic market for investors over the years and patients. Mm-hmm. It's evolved a lot. There's a lot of drugs out there now that work pretty well. Can you talk about the evolution of the market from when you guys started to what it looks like today, and then also where is it going and how do you guys factor in? It started, I mean, as I said 20 years ago, the market was totally unknown. Nobody knew it would reach the magnitude that we've seen today. It took a lot of sort of pioneer thinking to think ahead and to devote to development into that area. Back then, it was the days of icatibant and Kalbitor and Berinert, it was about managing attacks. I think now that through to the other therapeutics that have come to the market, we are now where we could say we're managing the disease as best as we can, but still some big unmet need. I think the vision is ultimately once you have in our view a efficacious oral therapy option that you really get into the realm of what we call controlling the disease. The aspect of feeling in control is something that we think is something that patients with HAE really are looking for. You guys have programs, like you mentioned, for both prophylaxis and on-demand acute. We can use it interchangeably, I guess. Yeah. You have phase 3 data now in hand for on-demand treatment of attacks. Mm-hmm. Tell us about the phase 3, what you guys learned? I mean, Maggie, do you take that one? Yeah, happy to. Yeah. Our phase III data read out in December of last year. We were happy to meet our primary endpoint and all 11 key secondary endpoints with statistical significance in a hierarchical fashion. We had to hit statistical significance each time, and if we missed it, then we wouldn't be able to hit it for any of the following endpoints. Really pleased with the data that we put out. Our primary endpoint was PGI-C a little better. That is time to initial symptom relief. That is in 1.28 hours. We also read out a new endpoint called end of progression. That's when the attack stops getting worse, which is a very important psychological piece for patients and for physicians. They know their medicine is working. That was in 17.5 minutes. There are endpoints throughout the whole cascade, but importantly, we also think that the time to complete symptom resolution in less than 12 hours was a really impactful endpoint to hit. Across the board, all of the endpoints met with statistical significance, numerically better than standard of care. These weren't head-to-head studies, so still placebo-controlled, but we were really pleased with the phase III data from December. With all the endpoints, and in phase two, you guys had a ton of data too. It all looked good. What's the benefit of having all of that data? What matters the most? Like, what do patients care about or doctors care about? Is that the same? Is it different? Yeah. I think that what matters the most is think of sort of put yourself in the shoes of somebody experiencing an attack. It's really first you have the feel of the attack coming on and you wonder now how is this gonna be, what kind of attack is this gonna be? First need to think about take the therapy and in the case of injectable, for example, in the on-demand side, there's a hesitation and then sometimes for patients to treat and there's a delay because you have to find the place to inject and it's also painful, so the patients are then in a little bit of a stressful situation. Should I take it? Or should I not take it? Or et cetera. It's the simplicity and the convenience of an oral to be able to have that portability to take it immediately, is very important for to have that, as I mentioned earlier, control. I feel I have this in my pocket. Mm-hmm. If I have an attack, I just take it anywhere. I could take it here on this panel. Mm-hmm We can continue to talk. Then of course, to really know that once I've taken this therapy, that this is gonna help me, not just to feel a little bit better, but really resolving the attack. I think that's where the data that we're so excited about for the deucrictibant is that it's not just the onset that is important because it gets the sense of the attack is not under control so. Mm-hmm So to speak. Having a fast onset is not so meaningful if it's gonna take more than 24 hours to resolve the attack. The totality of the whole experience from the beginning to the complete resolution. Mm-hmm when you go back to your normal life, and you can go to that job interview or that wedding or whatever that is important to you in your daily life. It's an interesting dynamic you talk about, like, the peace of mind knowing that you have an oral drug because these can also be stress induced or stress exacerbating. Having, like, that psychological, like, this will be okay, has gotta be helpful too as well. Mm-hmm. Mm-hmm. The market was easier to track before icatibant went generic, and now the past few years have been kind of hard for us to kind of pinpoint how big this market is. We also have Orladeyo, an oral plasma kallikrein inhibitor approved and selling. What's kind of the work you guys have done to better understand what the on-demand opportunity is? Well, I think the market size we think is estimated now to be about $600 million in the US. It's about 20% of the total HAE market. We think that the on-demand market is certainly a viable market. We think that it's gonna be dominated by oral therapies in the future because of the reasons I just mentioned. I mean, the simplicity and the speed of treatment, portability, these are all that leaves almost no argument left for having an injectable in the oral segment. I think that that will also lead to further growth in the on-demand segment. Mm-hmm. More attacks will be treated because of this lower hurdle to treat, the overall better outcome for patients. Mm-hmm the lower burden in the healthcare system. We definitely think that the on-demand market is a viable market. Until you have 100% attack reduction on the prophylactic side, anybody on prophylaxis is, by definition, also an on-demand patient because there's gonna be some breakthrough attacks. Yeah. The on-demand market really is viable. Yeah, it gets complicated pretty quick in my shoes, is how to think about that market growth. Yeah. Because if we're just thinking about our people have the drugs now, they're using them to some extent, but they're not using them as well as they should. Mm. How do you guys think about, like, and maybe you're seeing this in some of your open label data, like, I'm more willing to treat an attack because I can do it more easily, and what could that mean for the opportunity? Not only are you gonna get patients switching from injectables, but they're gonna be switching and then using the drug more. Exactly, yeah. Yeah. I mean, that's my point. That you would see the oral taking over the on-demand segment, and then more oral attacks will be treated. I think again, it's just as important in the prophy segment to have what patients are looking for also is this, as I mentioned, the reliable efficacy. Mm-hmm Really be able to have confidence that the attack is gonna be resolved, and dealing with only one dose. Like in any area there, efficacy is gonna be paramount and really give the patient that comfort of being able to control the attack. I think. I think. Another important aspect is that right now, of that $600 million in the U.S. on-demand market, about 53% of those people are treating with icatibant. Mm. Right? If you're able to have a more effective oral drug that uses the same mechanism of icatibant, you may be switching generic pricing back to branded pricing. Mm-hmm which changes the market size as well. That's a good point. Mm. A very good point. How do you guys think about, you know, commercial planning in the acute? Because you have an NDA submission coming up soon. When do you guys start building out infrastructure and thinking about launch prep and what do you have to do, and, you know, how should we think about, you know, a launch in this market? Mm-hmm. Yeah, that's going on as we speak. It also even started a couple of years ago, when we started to build the core team of people in the commercial team that they also have experience with HAE and launches and then from other companies that have worked on HAE. That's already started. What we are focusing on is building the awareness of Pharvaris in the community. We have the disease awareness campaign, Deflate HAE. That is ongoing. Of course, this coming year will be key to build up the organization and then ramp up and get the team together to be ready for the launch. That's fully underway. It's nice to have that data and then pivoting the prophylaxis, which is a market that I think investors know more because there's more drugs. It's a larger opportunity. Talk to us about where you guys are in development there. Yeah. On the PROPHY side now, we have CHAPTER-3 that's ongoing, phase III study, guided to read our top-line data in Q3 of this year. We're looking forward to that. Then, of course, continue then on with the filing that and the NDA based on that. We're already. The filing team is already starting to do some preparations for the PROPHY filing to- Mm-hmm Just to leverage to some obviously some synergies there with the same drug and all that. A lot of materials that are needed for the PROPHY filing is also going into the on-demand filing already. That's so you could get a head start when we have the data. That is some nice synergies from a regulatory perspective, having a lot of the overlap. Can you remind us what you saw in phase II that got everybody excited? Yeah. Our CHAPTER- 1 data read out in December of 2023. In our primary endpoint, we had 84.5% attack reduction. In our open label extension, we've maintained that attack reduction and even saw a further dip. We saw about 92% attack reduction in open label extension. Our goal with the phase III is to repeat the phase II data. We're hoping to have 80%-85% attack reduction. That would put us squarely in competition with approved injectables right now. Mm-hmm. Numerically better than the approved oral that's at about 44% attack reduction. We'd love to continue to see a clean safety profile, where this is gonna be the six-month dosing of deucrictibant, so it'll be the longest extended release dosing that we've seen. We have open label extension data of up to three years on deucrictibant, so we're still pretty confident in the safety profile that we've seen. Mm-hmm. There's gonna be some interesting data around attack-free rates, and also for us, it's quality of life data that's gonna be really important. How are people impacted by having a simple daily oral that has the same efficacy as their Takhzyro, Haegarda, Cinryze, or if they're able to take it just as a daily oral, that could be really impactful for their quality of life. What are you guys learning from the open label extension in terms of the patient experience with deucrictibant in ease of use and switching over? Are there patients that switch from particular things, or is it all across the board? Yeah. Our open label extension for the phase II that we just read out was still using the BID dosing, so still a bit of patient burden to have to dose twice a day. We're really hearing a lot of excitement around the fact that people are, I think it's that they're, like, experiencing less than an attack a year, one breakthrough attack a year, so it's pretty high attack-free rates. There's a lot of people who switch from Orladeyo over to our open label extension because they are seeking an oral therapy that now they're seeing some of the efficacy and a little bit higher tolerability than they saw in that. There's still people who are on injectables who desire to have an effective oral. What could go wrong in the phase III? 'Cause, you know, I don't think we've ever seen a phase III HAE study fail, but when you say, "We wanna hit our phase II mark," is there any difference in dosing population? The timing of the endpoint's slightly different, but, you know, what could cause any kind of reduction in effect that you know, might worry a little bit? Yeah. Nothing specific, I mean, looking at sort of compare the efficacy between the two trials. I mean, there's always this general risk factor when you go from a compact phase II to more broader phase III with more sites and more countries. Mm-hmm more, maybe more heterogeneous population. We had that, of course, also in RAPIDe-3 in the on-demand, and we were very pleased to see that that was not the case. We have site overlap to a large extent also with the PROPHET trial, and the quality of the execution and all that was very good. We hope to see that repeated in the CHAPTER-3 trial. Do you think there is wiggle room there? Because we've seen Orladeyo do very, very well with, you know, subpar efficacy compared to the injectables and still, you know, pretty good adoption. How do you guys think about is there wiggle room for you to be, you know, better than Orladeyo, not as high as an injectable and still see market adoption, or is that story already told with Orladeyo? Well, I mean, I think the higher, the better, of course. Mm-hmm. It has to be meaningful in the eyes of the patient and the treating physician. It's hard to put a real number on that, but I mean, some feedback that we've heard earlier on was even before we knew our phase two data was around sort of 70% seems to be sort of a- Yeah breaking point there. As Maggie said, we're hoping to see better than that or see something more comparable to the phase two. Even at that lower level, it would still be competitive. The higher, the better, it's obvious. A little bit of a different market dynamic here. In the acute setting, I think the growth story makes sense with treating more attacks. Prophylactic, can you talk about the evolution of that market? What's, you know, being used today, and how do you guys fit in there, and how should we think about the evolution of the market if deucrictibant does become available? Yeah. We see growth and more as more therapy options become available, more patients go on therapy. Also on the global scale, of course, the prophylactic segment is not as large as it is in the U.S., in other countries. But there is the same trend that is growing. The trend is towards prophylaxis. It's also a growth factor. I think that's. Of course, in our case, we also see this additional potential in acquired angioedema, which is today about 10% of the market, but potentially underdiagnosed because of the awareness of the treating physicians in these underlying diseases. So it may be lower than it is in the HAE community. Mm-hmm. That's also with our strategy to go for a label also for that acquired angioedema that could allow us then to uncover more and help more patients also in that area. Concurrently going for a label with acquired? Yeah. We have initiated a phase III trial, 24 patients, in acquired angioedema. Also, obviously in consultation with the regulators and Mm-hmm the protocol. We get a lot of support from the regulators and encouragement to also for us to explore normal C1. Mm-hmm which is an area where today I think is about 20% of the market. That is the patient segment, and sometimes also called type III. Mm-hmm. Where the pathway of bradykinin production is different. So that it's the best place to address that is at the end of that cascade. Mm-hmm ... the bradykinin inhibition. We see an advantage for deucrictibant also for that patient segment. Yeah. You talked about this earlier, but working at the bottom of the cascade, that should allow you to have opportunities that other drugs that work, you know, plasma kallikrein inhibition or different targets. Mm-hmm You know, either can't address or can't address as well, right? Right. Exactly. When we think about prophy and acute, you guys will also be in a position where you'll have options for both of these market segments. I think, you know, what we need to start realizing more is the synergies that provides you as a company. Strategically, can you talk about the advantages that benefits you? It gives us, I mean, advantages and differentiation in the multiple areas. I mean, even in the sense now from a timing perspective because we're launching on-demand prior to prophy. That basically leading the way for the prophy launch. Having the simplified prescription and the ability to choose between the two. It also, in the evolution of a patient's disease experience, where the severity or the frequency of attacks may change over time. Mm-hmm. The ability then to move on from this something that you feel works for you to in, let's say, on-demand, and then go to prophy or even the other way potentially. That having the whole spectrum of patient choice is a key differentiator for us. Is there any risk of, you know, I'm having an attack, I'm using this one mechanism, then using more of the same mechanism to try and stop the attack? Or is it a drug exposure level primarily, or is it a mechanistic issue? It is all about exposure. I mean, even in the kallikrein, if you have a breakthrough attack on the kallikrein, you can also take another kallikrein rescue. Mm-hmm. That doesn't have to be the same mechanism. Okay. Having said that, today I believe icatibant is actually the most widely used rescue for breakthrough attacks. Mm-hmm. That's the confidence in the icatibant we think also that could play over to deucrictibant given the mechanism. What about the specialty pharmacy and the hub and the white coat service where you can better manage the patients with both products? Because we hear that a lot from HAE companies. Mm-hmm the ability to, you know, tailor care and need for what they have. When you also have an option like, hey, if you're having, we know that we could treat you better acutely. Mm-hmm If you're on our prophy as well. Yeah. That's a great question. Yeah. It's actually one of the really great synergies that we have on our commercial front, is the ability that you have one point of contact for both your prophy and your on-demand. The idea would be all things go the way we want them to. Our on-demand deucrictibant IR is already on the market. People have established relationships with their case managers, and the day that you have a prophylactic approval, those case managers can be in contact with their patients and say, "Next time you go into your physician, ask about deucrictibant XR because you've been on IR for nine months and you've loved your experience there." It's a really important aspect of our commercial strategy. How do you guys think about number of reps needed for, you know, the launch? Then my guess would be you could kind of onboard everybody for acute, and then you just have leverage in the system for prophy. Once again, HAE is super relationship based, and so the fact that we will already have our 40 salespeople in the US already for nine months before we even have a prophylactic product is a great way to be able to establish relationships with physicians. Then there's already. You know, you have one point of contact, and you have two products to sell. In the last minute or so, we talked about kind of what's coming next. If we could, you know, as a wrap-up, talk about the next 12-18 months, what's on the horizon for you guys in terms of potential catalysts, and then also remind us of the cash position. The key catalyst, of course, is the top-line prophy in the third quarter, then the filing of the NDA, and then down the road, the PDUFA date. On-demand also the filing in the first half of this year, and then looking forward to hopefully get approved in next year and the launch. Those are the key things. We also haven't guided specifically on any top-line for the acquired angioedema trial yet. It's still early days there, but we have initiated and so that is also something we're looking forward to. If timing works out as we hope, then there is the potential for a joint filing with the prophy filing. But that's of course subject to the timeline working out, but which is a little too early to say. The balance sheet is in a very good position now. Yeah. The balance of cash runway is just in the first half of 2027. We had EUR 360 million at Q3, the most recent reporting date, which was Q3 last year. We have phase III data this year, two potential launches in 2027, and potentially acquired angioedema as a bonus. Mm-hmm. It's a lot to do, guys. Yeah. Yeah. Well, we appreciate you coming today and giving us the story and what to look forward to, and we'll be interested in tracking all the progress. Yeah. Great. Thanks. Thank you.