Pharvaris N.V. (PHVS) Earnings Call Transcript & Summary

My name is Jeremiah Lorentz. I'm one of the equity research analysts here at Bank of America. It's my pleasure to introduce our next presenting company, Pharvaris. Today, we'll be joined by CEO, Berndt Modig. Take away.

Yes. Thank you, and welcome, and good morning to [indiscernible]. And to show you a brief presentation. It's only 15 minutes. So if you have questions or want to follow up, we invite you to reach out to us either to us here or to the over the website on the IR contact. So I will be making some forward-looking statements, and I also refer you to our SEC filings are also available on our website. So Pharvaris is a company that is focusing on bradykinin-mediated angioedema. And as It says, pioneering science for patient choice. What we mean by that is the choice of the therapy, how to best treat an indication in bradykinin-mediated angioedema. HAE is one form of bradykinin-mediated angioedema. And we have 2 late-stage programs at the moment in Phase III with our molecule deucrictibant which is differentiated in the sense that it has -- it's also both prophylaxis and on-demand treatment. And HAE is bradykinin-mediated angioedema is a large global market, is predicted to grow to about $5.2 billion in the next few years into 2036. It's also a very dynamic market that's seen several new products over the last couple of decades. And what we have seen is that there's still a large unmet need that I'll talk more about later for people living with HAE. And what we've also seen that there is no real sustainable first-mover advantage for any new entrant. It's always the next step to fulfill an unmet need in the space. And we have strong fundamentals, well funded. And also, I should say, in the team in our R&D team and our commercial team, more than half of our people have prior experience in this therapeutic area. So hereditary angioedema is a genetic condition. It's significant burden and impacts the quality of life. It's associated with unpredictable attacks of swelling in the deeper layers of the skin and the mucus membranes. And it's a -- these attacks occur very unpredictably and can happen any time. They mostly affect limbs and hands and face, but can also affect upper respiratory airways and intestinal GI areas. And the upper airway attack is always considered potentially life-threatening. And the prevalence is about 1:30,000 to 1:80,000 individuals globally. You see here on the slide here that there are some pictures of the patient with experiencing an episode of an attack. And the quality of life impact is very significant. And an untreated attack takes about 5 days or so to resolve on its own. So it is a reversible condition, but it has a big impact. In the histogram here, you see on the chart, you see the attack frequency and most patients have around 12 to 24 attacks per year. Some patients have many more. And this also is one of the factors that determines how a patient will treat HAE, either prophylactically preventing attacks or acute on-demand to treat an attack when it occurs. So deucrictibant, which is our molecule, is a B2 receptor antagonist. It's the same mode of action as another therapy that some of our members of our team were involved in developing in a prior company, Icatibant. And it's a new chemical entity. It's a small molecule orally available. And to our knowledge, the first and only small molecule orally available B2 receptor antagonist. And we developed deucrictibant in 2 different products, one for prevention, which you see here in the green chart to the left and one for treating acute attacks in an immediate release capsule. And the properties of the molecule because of the longer half-life, it also makes it suitable for both of these types of formulations. And these charts represent the PK profile of the 2 different formulations. We're using the same drug and the same active ingredient. And I say, we're the only company that really has that in -- with the same drug for 2 different products to treat acutely or prophylactically. And the exposure levels that you want to achieve in the plasma concentration is above the red dotted line that you see here. It's the [indiscernible] 85 effective line, which in the case deucrictibant is about 13.8 nanograms per milliliters. So the goal is to maintain exposure above this threshold level. And in case of the extended release formulation, you see that the sustained coverage over exposure over 24 hours from day 1. The onset is slower than the acute formulation, but within a few hours, you have coverage. And it's also reached a steady state in a few days. On the IR side, you see the capsule. It has a very fast uptake, which makes it designed and suitable for treating acutely. And also because of the half-life, a sustained coverage and exposure to ensure that the attack can be resolved effectively. This is our pipeline. So in HAE, we have 2 Phase III studies, as I mentioned, the RAPIDe-3 in on-demand and CHAPTER-3 in prophylaxis. These are ongoing. And we also have in parallel open-label studies that are also ongoing. And then we have the top line data is expected for the on-demand study and we've guided 1Q '26. And the for the prophylactic trial, the top line data is guided to second half of '26. And the dark blue part here is another form of angioedema called acquired angioedema. It's not caused by genetic mutation, but it has the same size and symptoms and the same clinical manifestations as very similar to HAE. And we are currently working a plan with -- also with the regulators to start a study for acquired angioedema at the end of this year using deucrictibant and that trial is designed to planned to deucrictibant beyond hereditary angioedema to bradykinin-mediated angioedema. And we also recently got an orphan drug status in Europe for this new indication, bradykinin-mediated angioedema, and we also have it in the U.S. for both on demand and for prophylaxis. So take a look at the data in our Phase II studies, starting with the prophylactic trial. You see here the percentages in attack reduction. And so what you look for in a prophylactic study is comparing the number of confirmed attacks compared to placebo. And we are very excited what we saw here, and this is the first time you see efficacy in the same range as with the current injectable therapies and -- but in an oral form with deucrictibant. So we saw in the 40-milligram per day, an 84.5% attack reduction compared to placebo. And in our open-label extension, then continuing from that, a further reduction of 93% attack reduction compared to the baseline in the Phase II trial as compared to the placebo. We also saw in the open label then a median attack rate of 0 for every month and 99% of days were symptom-free. For the Phase III study in prophylaxis, it's the basic design you see on this slide. It's again, the same design as Phase II comparing the number of attacks and attack reduction compared to placebo. So patients are randomized 2:1 in an active arm and in a placebo arm. And then with the objective to measure the confirmed attacks and also looking for other safety parameters and continue to build the safety database. The study is essentially powered with 81 patients for safety, and it uses the same dose as we had in the Phase II now with the extended release tablet formulation. You see a small picture of it here on the top of the slide. Moving on to the acute study. Again, Phase II data on this chart, the graph here is an illustration or conceptual illustration of the progression of an attack, the onset in the red part and then the symptoms increase and then the symptoms then resolve over time. And what you look at in the clinical trial are the different stages of development and ultimately leading to the complete resolution of the attack. And we also have in our Phase III study, a new endpoint called end of progression, which is right at the beginning, the first point after treatment that you measure an effect. This is an endpoint that then if positive, we can also include potentially in our label if approved. And the primary endpoint is onset of symptom relief, which is the second section here on the progression of attack. And then the later endpoint, secondary endpoints are the resolution of the attack and ultimately the complete resolution of attack. So this whole scenario starting from the onset of the attack to the ultimate resolution are all very important and sustained efficacy and leading to the ultimate resolution of attack in a reasonable time frame, but that's when the patient then basically is able to regain function and go back to work and do what they were doing and have the attack behind them. So you see it here clicking through end of progression, onset of symptom relief, substantial symptom relief and complete symptom relief. The Phase III study is designed as a crossover study in treating 2 attacks in an enrollment of approximately 120 patients, including adolescents. We recently completed the enrollment in that study and are now accumulating the remaining attacks that we need to close the database. We guided the top line data currently to Q1 '26. And the endpoints are the onset of symptom relief being the primary endpoint in using something called Patient Global Impression of Change, PGI-C. And then the further secondary endpoints are time to end of progression that I mentioned earlier, which is the first measuring point. And then the patient global impression of severity and use of rescue medication. And incidence of treatment with emerging adverse events and safety of course. And here on the picture to the right, you see the softgel capsule. It's also very small softgel capsule, easy to swallow. It's also the portability of that is important for a patient, again, having this condition to be able to have access to therapy very quickly in the case of an attack. So Pharvaris as a company, our aspiration is to become a leader in the bradykinin-mediated angioedema space and rooted in a deep commitment to engage with the HAE community. And we -- as I mentioned earlier, many of our team have been involved in HAE for many years, up to 20 years with some of us. And a lot has evolved in the space in the last couple of decades that we're looking forward to potentially become the standard of care in ODT window long-term prophylaxis market, become the preferred leader in the preferred therapy and long-term therapy and also beyond leverage our portfolio with B2 receptor antagonist mode of action, all subject to, of course, clinical trials remaining in Phase III and ultimate approval of the deucrictibant. So that's a quick overview. So I don't know if we have time for questions, but thank you very much.