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

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 [indiscernible]. Over to you, Berndt.

Good. Thank you. Thank you so much. And hi, everyone, and welcome to the Pharvaris presentation. And I'm glad to see that everybody could find a seat. And also thank you to JPMorgan for the opportunity to present here today. So just to go through the usual disclaimer. We are -- I'll be making some forward-looking statements and subject to some uncertainties and risks. So I'll also refer you to our SEC filings, including the risk factors in our 20-F statement. So Pharvaris -- at Pharvaris, we're pioneering science for patient choice for hereditary angioedema. And we are a late-stage company with 2 late-stage programs and our lead asset is deucrictibant, which is an orally available small molecule targeting the validated bradykinin B2 receptor. And I'll show you also in the presentation results from a 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 the data that we see 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 in HAE appear satisfied with the treatment history has shown that the availability of a more efficacious, better tolerated and convenient alternative drives the dynamic switch. Pharvaris with strong fundamentals, we are now -- have 2 pivotal Phase III trials underway designed to differentiate the current standard. And also 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, and we are -- the long -- HAE is a long genetic condition, with a significant burden. It's characterized by swelling -- attacks of episodes of swellings and with the frequency, location could vary. It's very unpredictable. It's really not known what triggers hereditary edema attack. It's thought to be caused by stress as a possible cause. And if untreated, such an attack may last up to 5 days. And you see here on the chart the attack frequency distribution. And most patients in an untreated state would have somewhere between 12 to 24 attacks per month -- per year and about once or twice a month. And there are about 1 to 30,000 to 1 to 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 -- long-term prophylactic. And the -- 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 ability of the patient and to reduce the severity of attack and that will 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 beta receptor antagonist, and it has the potential to address the unmet need for people living with HAE. You see here that we have with the same active ingredient, we have 2 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 the enough duration to resolve an attack. And on the left side here, you see our XR extended-release tablet formulation of deucrictibant with -- which is designed and more sustained coverage in the PK profile to provide efficacy over a 24-hour period to allow for once-daily dosing. Our pipeline is, as I mentioned, 2 Phase III -- ongoing Phase III trials and one in on-demand and one in prophylaxis and also with the ongoing open-label extension trials. We have also a program that we also announced this week that to plan to embark on an additional indication in bradykinin-mediated angioedema -- acquired angioedema, and I'll talk more about that later. So starting with the prophylactic development. In our Phase II trial, we had top line data in December of '23, and we saw the primary endpoint was met with 84.5% reduction in monthly attack rate. We saw 92.3% reduction in occurrence of moderate to severe attack, 92.6% reduction in attacks treated with on-demand medication. In other words, the attacks that required rescue medication. And we saw clinical 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. And the median attack rate in the long-term extension rate was 0 for every month and 99% of days symptom-free. We are -- as I mentioned earlier, for the prophylactic formulation, it's a long-term extension release formulation that maintains exposure above the therapeutic level for at least 24 hours. And you can see that here in the PK curve in the green line that based on what we've seen in the PK study supports once daily dosing. And 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 2-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, and we anticipate the top line data in the second half of '26. 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 met the primary endpoint and significantly reduced the attack symptoms versus placebo, showed end of symptom progression in 20 to 26 minutes and a fivefold reduction in the use of rescue medication and an onset of symptom relief in 2.4 hours and 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. And also here, again, 98.5% of attacks were resolved within 12 hours, 97.7% of attacks by 12 hours and hours -- 2.6 hours median time to reduction of attack severity by PGI-S. And 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 and it's a crossover design using the 20-milligram dose in the -- of the immediate release capsule. You see a picture of it here up in the top right corner. And with the endpoint of PGI-C, the sign of symptom relief, and Patient Global Impression of Change rating of at least a little better for 2 consecutive time points within 12 hours. So the U.S. -- in the U.S., the significant growth of the long-term prophylactic and the demand therapy market expected over the next decade. And 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 by 2036. And that growth is driven by new options, increased convenience and continued paradigm shift, as I mentioned, from on-demand to prophylaxis. And the -- on-demand side, we also see -- expect 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 the number of patients that are getting new prescriptions. And on the bottom part, you see the reduction. And you see about 5% of switches in each quarter and also you can 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 the last decade. And I think it becomes clear if you look at the different products that it's 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 new -- better ways to treat. And it's what we've seen historically are the products that are -- 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. So about 86% of patients who are on a prophylactic treatment are interested in medications that could improve the -- make it easier to administer and improve to reduce the treatment burden. And patients -- there's about 61% of patients wish that they could treat HAE more discretely. If, for example, I had an attack here in this speech, I could take an oral tablet with the glass of water and continue the presentation. So deucrictibant is differentiated in -- based on what we've seen so far and also to be confirmed in our future trial both in oral on-demand and prophylaxis. And it's the only HAE therapy that allows for oral administration in both prophylaxis and on-demand in a single oral pill with a once oral dosing for prophylaxis in XR and the rapid single dose resolution for HAE attacks in on-demand. For the prophylaxis, also the rapid time to steady state is a factor that has the potential to achieve steady state within 2 to 3 days, providing protection against HAE attacks on the initial day of initiation. On the on-demand side and again, rapid absorption is essential also within 15 to 30 minutes, deucrictibant IR reaches therapeutic exposure, resulting in the halt of an attack progressing within 30 minutes. And the -- 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. And 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. And with the mechanism that we have with deucrictibant is a bradykinin inhibition. And 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. So in acquired angioedema, there is -- this is an overview of an investigator trial that has been conducted in the Amsterdam University Medical Center. And it's exploring both first in the on-demand setting in a prophylactic treatment with deucrictibant. And also to the right here, the ONCE-AID study, which is a long-term extension using the extended release tablet formulation. And people with acquired angioedema, the estimated prevalence is approximately -- estimated to be approximately 10% of the HAE type 1, 2. And this is the overview of this [ POP. ] It is a ONCE-AID study with the prophylactic XR tablet for the prevention of acquired angioedema. And this is only 4 patients with the duration of up to 18 months. And 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 for me first, and then I go to the audience and from the iPad too. For me, what brings you confidence in the extended release formulation that you'll be using in the Phase III prophylactic study?

Yes. Peng?

Sure. Yes, that's indeed a great question that actually, as Berndt presented in the slide deck that to show that for the extended release formulation, we actually conducted 2 studies to assess no matter for single dose or multiple dose extended-release formulation to show to -- for the total exposure for 40 milligrams that extended release tablet is very comparable to the 20-milligram twice daily that BID at the immediate release formulation, we tested in the CHAPTER-1 study. Meanwhile, we really want to highlight with the PK pharmacokinetic profile showed in extended release formulation, the Cmax is dramatically dropped to reduce potential at 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, that with extended release formulation that used in our pivotal study, it further increased the confidence to cover the variability from the pivotal study. I also want to mention that in addition to the PK/PD assessment in the healthy volunteers, Berndt also showed a cord angioedema study and also he highlighted that in the open-label extension up to 18 months treatment despite a small sample size, 4 patients with extended-release formulation shows almost attack-free up to 18 months. From the other side, with a small sample size, but it indicates the great efficacy and also well-tolerated safety profile. This further derisk that we use extended release formulation in the pivotal study.

Great. Thank you. Any questions from the audience? Maybe we can go to the iPad for the time being. So I've got here. How will gene therapies impact the HAE space?

Thank you. So 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. And we also see gene therapy entering HAE. Now 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. And so we believe that while this is interesting, we don't see a radical impact on the market as such.

How do you see the new potential -- new entries of garadacimab and donidalorsen to impact the HAE space?