Ladies and gentlemen, welcome to the 43rd Annual JPM Healthcare Conference. This afternoon, we have Berndt Modig, CEO of Pharvaris, who will be presenting on behalf of the company. Berndt is joined by Peng Lu, CMO; Wim Souverijns, CCO; and David Nassif, CFO and CLO. Over to you, Berndt. Thank you. Thank you so much. Hi, everyone, and welcome to Pharvaris' presentation. I'm glad to see that everybody could find a seat. Also, thank you to J.P. Morgan for the opportunity to present here today. Just go through the usual disclaimer. We are going to be making some forward-looking statements and subject to some uncertainties and risks. I'll also refer you to our SEC filings, including the risk factors in our 20-F. Pharvaris, at Pharvaris, we're pioneering science for patient choice for hereditary angioedema. We are a late-stage company with two late-stage programs. Our lead asset is deucrictibant, which is an orally available small molecule targeting the validated bradykinin B2 receptor. I'll show you also in the presentation results from randomized phase II trials and their ongoing extensions that demonstrated a differentiated profile based on that data for preventing and treating HAE attacks with an injectable-like efficacy based on data that we've seen and a quick onset of action. Hereditary angioedema is a large global market and predicted to grow to about $5.2 billion by 2036. People living with HAE appear satisfied with the treatment history. It has shown that the availability of a more efficacious, better tolerated, and convenient alternative drives the dynamic switch. Pharvaris with strong fundamentals. We now have two pivotal phase III trials underway designed to differentiate the current standard. The team at Pharvaris has a track record in HAE, both in the development side as well as the commercial side. We had EUR 305 million in cash at the end of Q3 last year. HAE is a rare genetic condition with a significant burden. It's characterized by swellings, attacks of episodes of swellings, and where the frequency, location could vary. It's very unpredictable. It's really not known what triggers hereditary angioedema attack. It's thought to be caused by stress as a possible cause. And if untreated, such an attack may last up to five days. And you see here on the chart the attack frequency distribution. And most patients in an untreated state would have somewhere between 12- 24 attacks per year, about once or twice a month. And there are about 1 in 30,000- 1 in 80,000 people living with HAE globally. The treatment goals for HAE is, according to the World Allergy Organization, to achieve complete control of the disease and to normalize patients' lives. And the view there that can really only be achieved with a prophylactic, a long-term prophylactic. And also the aim to treat attacks on demand is to reduce the duration, to have a reliable and minimize the impact of an attack on the functional availability of the patient and to reduce the severity of the attack and to lead to normal life, which is what people living with HAE are looking for. Deucrictibant, which is our molecule, is a, as I said, a bradykinin B2 receptor antagonist. And it has the potential to address the unmet need for people living with HAE. You see here we have with the same active ingredient, we have two formulations. And one is an immediate release capsule with a PK profile that's targeted to develop to optimize for treating an acute attack with a fast onset and enough duration to resolve an attack. And on the left side here, you see our XR extended-release tablet formulation of deucrictibant with this designed then for more sustained coverage in a PK profile to provide efficacy over a 24-hour period to allow for once-daily dosing. Our pipeline is, as I mentioned, two phase III ongoing phase III trials and one in on-demand and one in prophylaxis, and also with ongoing open-label extension trials. We have also a program that we also announced this week that we plan to embark on an additional indication to bradykinin-mediated angioedema called acquired angioedema. And I'll talk more about that later. Starting with the prophylactic development, in our phase II trial, we had top-line data in December of 2023. We saw the primary endpoint was met with 84.5% reduction in monthly attack rate. We saw a 92.3% reduction in occurrence of moderate to severe attack, 92.6% reduction in attacks treated with on-demand medication. In other words, attacks that required rescue medication. We saw clinically meaningful results in all other endpoints and also, importantly, also well tolerated at both doses. This is the overview also of the open-label extension data. We did a data cut in September last year. We saw consistent data with the phase II trial with an attack reduction of 93% based on baseline, the baseline being the baseline in the placebo group in the CHAPTER-2 trial. The median attack rate in the long-term extension rate was zero for every month and 99% of days symptom-free. We are, as I mentioned earlier, for the prophylactic formulation, it's an extended-release formulation that maintains exposure above the therapeutic level for at least 24 hours. You can see that here in the PK curve in the green line that, based on what we've seen in the PK studies, supports once-daily dosing. We also have patent applications filed with this formulation. The CHAPTER-3 data, which is now the phase III data that we just initiated, is a two-part global phase III study. It's designed with the screening and then over a 24-week period compared to placebo with the endpoint to evaluate the reduction of attacks compared to placebo in that time frame. We look to enroll about 81 patients, including adolescents and adults living with HAE. We anticipate the top-line data in the second half of 2026. Now over to on-demand. The, again, phase II data in RAPIDe-1, the phase II study for deucrictibant in HAE. This is an overview of the key results from that study. It showed it met the primary endpoint and significantly reduced the attack symptoms versus placebo. It showed end of symptom progression in 20-26 minutes and the five-fold reduction in the use of rescue medication and an onset of symptom relief in 2.4 hours. It's also well tolerated at all doses. The RAPIDe-2, which is the long-term extension study of RAPIDe-1, again showed consistent results compared to the phase II study. Also here, again, 98.5% of attacks were resolved within 12 hours, 90.7% of attacks by 12 hours and 2.6 hours median time to reduction of attack severity by PGIS. 86% of attacks were treated only with a single dose, which is a key aspect in an on-demand therapy. The RAPIDe-3 open-label extension, the phase III study, RAPIDe-3, is also a global study. It is crossover design using the 20 mg dose of the immediate release capsule. You see a picture of it here up in the top right corner. It has the endpoint of PGIC, the onset of symptom relief and patient global impression of change rating of at least a little better for two consecutive time points within 12 hours. In the U.S., the significant growth of the long-term prophylactic and the on-demand therapy market expected over the next decade. The focus and the trend in hereditary angioedema goes towards prophylaxis. That's where we anticipate the majority of the growth expected to grow to about $4 billion in about 2036. That growth is driven by new options, increased convenience, and continued paradigm shift, as I mentioned, from on-demand to prophylaxis. On the on-demand side, you also see expected growth by new options, increased convenience, and also more options with more convenience also could result in an increased treatment rate. The HAE market is very dynamic with people actively seeking a better product. On the right side here, you'll see switching data in the U.S. On the top part here are gains and new prescriptions in prophylaxis and on-demand and a number of patients that are getting new prescriptions. On the bottom part, you see the reduction. You see about 5% of switches in each quarter. Also you see a growth over time because more prescriptions, new prescriptions are larger than prescriptions lost. You can also see here on the left side. This is a chart of the launches of products in HAE over the last years and last decade. I think it becomes clear if you look at the different products that it being first to market is not the key. There's no real first mover advantage sustainable in HAE. People living with HAE are looking for better ways to treat. It's what we've seen historically are the products that make improvements in efficacy, tolerability, or safety also lead to stronger uptake and dominance of the market. For people living with HAE, there's a desire for alternative routes of administration, reflecting the desire to move away from injectables based on research that we have seen. About 86% of patients who are on a prophylactic treatment are interested in medications that could improve the ease of making it easier to administer and improve to reduce the treatment burden. Patients, about 61% of patients wish that they could treat HAE more discreetly. If, for example, I had an attack here in this speech, I could take an oral tablet with a glass of water and continue the presentation. Deucrictibant is differentiated based on what we've seen so far and also to be confirmed in our future trial both in oral on-demand and prophylaxis. It's the only HAE therapy that allows for oral administration in both prophylaxis and on-demand in a single oral pill with the once-oral dosing for prophylaxis in XR and the rapid single dose resolution for HAE attacks on demand. For the prophylaxis, also the rapid time to steady state is a factor that has the potential to achieve steady state within two to three days, providing protection against HAE attacks on the initial day of initiation. On the on-demand side, again, rapid absorption is essential. Also within 15- 30 minutes, deucrictibant IR reaches therapeutic exposure, resulting in the halt of an attack progressing within 30 minutes. And also the longer effective exposure is relevant for the on-demand, which is to get a high rate of single dose attack resolution. Here is the next we're going to talk about acquired angioedema. And the bradykinin B2 receptor inhibition is broadly applicable to across angioedema and not just hereditary angioedema. There are other forms of acquired angioedema, the C1 deficiency, and also patients with normal C1 and, of course, hereditary angioedema. This is a complex slide, but the basic point here is that the mechanism, the pathways associated with ultimate bradykinin release in angioedema that causes the signs and symptoms and at the bottom of the cascade. With the mechanism that we have with deucrictibant is a bradykinin inhibition. At the end of the cascade, we see that that has potential advantages and also enables you to treat all forms of angioedema independent of the pathway. In acquired angioedema, this is an overview of an investigator trial that has been conducted in the Amsterdam University Medical Center. It's exploring both first in the on-demand setting and the prophylactic treatment with deucrictibant. Also to the right here, the ONE-STATE study, which is a long-term extension using the extended release tablet formulation. People with acquired angioedema, the estimated prevalence is estimated to be approximately 10% of the HAE type 1, 2. This is the overview of the ONE-STATE study with the prophylactic XR tablet for the prevention of acquired angioedema. This is only four patients under duration of up to 18 months. During that time frame, except for one attack in the second day of one patient, these patients have been attack-free for the whole study so far. That concludes the presentation and open for questions and also from our team. Maybe one from me first and then go to the audience and from the iPad too. For me, what brings you confidence in the extended release formulation that we're using in the phase III prophylactic study? Yep. Sure. Yes, that's indeed a great question that actually as Berndt presented in the slide deck, that it will show that for the extended release formulations, we actually conduct two studies to assess no matter for single dose or multiple dose extended release formulation to show for the total exposure for 40 mg that extended release tablet is very comparable to the 20 mg twice daily that BID, that immediate release formulation we tested in the CHAPTER-1 study. Meanwhile, we really want to highlight with the PK pharmacokinetic profile showed the extended release formulation, the Cmax is dramatically dropped to reduce potential risk for side effects. Meanwhile, the trough level significantly increased. As we know for the HAE treatment development, typically efficacy is driven by trough level. Therefore, with extended release formulation that is used in our pivotal study, it further increased that confidence to cover the variability from the pivotal study. I also want to mention that in addition to the PKPD assessments in the healthy volunteers, Berndt also showed acquired angioedema study. He also highlighted that in the open label extension up to 18 months treatment, despite the small sample size, four patients with extended release formulation shows almost attack-free up to 18 months. From the other side, with a small sample size, but it's indicate the great efficacy and also well-tolerated safety profile. This further de-risk that we use extended release formulation in the pivotal study. Great. Thank you. Any questions from the audience? Maybe you can go to the iPad for the time being. So I've got here, how will gene therapies impact the HAE space? Thank you. I think the world is excited about gene therapy in general. There are a lot of therapeutic areas where there's a lot of progress. We also see gene therapy entering HAE. The difference between HAE and some of these other therapeutic areas is that while academically very interesting, they are very well-known, very well-established conventional therapies that do their job, that work very well. We believe that while this is interesting, we don't see a radical impact on the market as such. Thank you. How do you see the new potential entries of garadacimab and donidalorsen to impact the HAE space? I can take that one as well. Thank you. It's exciting times in HAE for people living with HAE because we see a lot of new options coming to the market. And when I joined Pharvaris, one of the reasons why I joined is that HAE is a rare disease that hopefully can become a poster child for rare disease in general, meaning that there's not this one single therapy that's being used to treat the condition. There are actually multiple options. There are multiple alternative therapies. And the long-acting injectables, garadacimab and donidalorsen, will add to that. So we also anticipate that this might help to reinforce the guidelines. And the guidelines, they say that no patient should suffer any attack. And the only way to do that is through prophylaxis. So, having new players coming to the market, particularly with Ionis, CSL is already present. This can strengthen and push the move from on-demand over to prophylaxis, which I think is in the interest of the community. Okay. Thank you. We got here. What are you doing to support enrollment in the CHAPTER-3 and RAPIDe-3 studies? I'm sorry, could you repeat that question? Sorry. Can you hear that? So what are you doing to support enrollment in the CHAPTER-3 and RAPIDe-3 studies? Yeah. So if I can also comment, the CHAPTER-3 is a two-to-one randomization, which is, of course, a way to make it more attractive to join the study. And also it has a globalization compared to phase II. It also adds more sites globally, also in areas where there's today very little access. And we also believe that the oral aspect of it makes it interesting for some patients to enroll in the trial. So I can also comment further. Yes. I I think indeed that highlight that we try to optimize our study design to help the enrollment. Meanwhile, we also think about it that are quite confident about the enrollment because that in spite of the several available treatments and multiple ongoing trials, actually that is a whole community, no matter for patients or physicians, are very excited by our CHAPTER-1 readout. As Berndt presented, that with our treatment, we show 85% attack reduction in this study and also less one attack per year still require rescue medication. So in the whole HAE world, that the patients have strong desire for our treatment for a long time. Therefore, with the data shared with the community and also as Berndt mentioned, we try to optimize study design for pivotal study and also have the open label extension study available for patients. After they finish pivotal study, they can roll over to the open-label extension and get that really that the treatment up to commercially available. All these that help our enrollment. Therefore, we think that our timeline for top-line readout we shared is quite reasonable. Any further questions from the audience? Thank you very much. Yep. Thank you for coming today.