Everyone, and thank you for joining the HC Wainwright 27th Annual Global Investment Conference. My name is Arabella, and I'm an associate on the Equity Research team at HC Wainwright. We hope you have a productive day of one-on-one meetings, company presentations, and panels. With that said, it's my pleasure to introduce Pharvaris. Pharvaris is a late-stage biopharmaceutical company developing oral bradykinin B2 receptor antagonists to treat HAE and other bradykinin-mediated diseases. From the company, I'm excited to introduce Maggie Beller, the Head of Investor Relations.
Thank you.
Maggie, the floor is yours.
Thank you, Arabella, and thanks to the HC Wainwright team for having Pharvaris here. During this presentation, I'll be making forward-looking statements. For a full disclosure of our disclaimers, please see our SEC filings. Pharvaris is a late-stage company with two pivotal Phase 3 studies reading out in the next 12 months. We have guided towards our on-demand program for deucrictibant in hereditary angioedema reading out in the fourth quarter of this year, and our prophylactic program having top-line data results in the second half of 2026. We plan to initiate an acquired angioedema Phase 3 pivotal study this year. In total, the HAE market is about $4.7 billion in 2036, and we intend to have a broader indication for deucrictibant in bradykinin-mediated angioedema.
Our team in commercial and clinical development has over 50% of our team as former HAE developers, and we currently have cash runway into the first half of 2027. Bradykinin-mediated angioedema is a broader umbrella under which hereditary angioedema falls. There are attacks that are spontaneous, stress-induced, and incredibly painful. If you have a swelling attack in your throat, it can be potentially fatal. Currently, there are several approved injectable prophylactic programs and one oral program, and then we also have many injectable on-demand programs and a recently approved oral on-demand in the HAE space. We intend to use our oral deucrictibant in both the prophylactic and the on-demand setting. Deucrictibant is a bradykinin B2 receptor antagonist, so it acts at the bottom of the angioedema pathway. Many other programs are higher up in the kallikrein system. They're kallikrein inhibitors.
We operate on the same mechanism as icatibant, which is currently the most widely used on-demand program in hereditary angioedema. Deucrictibant is a single molecule that we have formulated to operate in two different therapeutic paradigms. There's an extended-release formulation that is acid stable through the stomach and then begins to degrade once you get into the gut and colon. This enables us to have once-daily dosing for optimal prophylactic use. We also have an immediate-release capsule, which rapidly achieves therapeutic exposure, which is optimal for the treatment of on-demand attacks. We hope to utilize this dual mechanism, or the single mechanism with dual formulations, to be able to treat and prevent HAE and other bradykinin-mediated angioedema attacks. This is our current pipeline for deucrictibant. As I mentioned, we have top-line data for the on-demand program in the fourth quarter of 2025.
We are working on completing enrollment in the prophylactic program with guided top-line data in the second half of 2026, and we plan to initiate our acquired angioedema study this year. Starting off with the on-demand program, the schematic that you'll see on the slide right now is a typical progression of an on-demand attack. You have the onset of symptoms, and then we hope to treat with deucrictibant. We ask our participants to qualify their attacks to an AMRA level of 20. Out of 100, they need to call a physician, confirm that they're having a real HAE attack, and then we measure these four important endpoints throughout the attack progression. End of progression is the first time that your symptoms stop getting worse. This is a new endpoint that we created.
We looked at the post-hoc analysis of our Phase II, and I'll share that data in a moment. If we're able to have our data read out the way that we hope, confirm our Phase II, then we'll be the only company that's able to market end of progression. Onset of symptom relief is our primary endpoint. This is a consistent endpoint with previous on-demand studies. We'll have the first time that, although not head-to-head, we'll be able to compare deucrictibant to other recently approved on-demand programs. Our primary endpoint is PGIC a little better. It's a self-submitted endpoint that you submit through an ePro device, and it's measuring change. Substantial symptom relief we've heard from patients and physicians is an incredibly important endpoint because that's when people can start to get back to their normal life. When can I return to running my errands or get back to work?
This is an important quality of life assessment. Complete symptom resolution is when you are no longer experiencing symptoms of your attack. With these four endpoints in mind, I have the next slide, which goes through each of our Phase II results for this. End of progression, we saw in the post-hoc analysis of our randomized clinical trial that people experience end of progression in 25 to 26 minutes. This is interesting because our first time point that we measured was 30 minutes. There's a range that people can be submitting that time point in. Our first endpoint for the Phase III is going to be 15 minutes. We hope to have even more clarity on what this end of progression endpoint is. Onset of symptom relief of 1.1 hours. This is by the same measurement that we'll be measuring in our Phase III.
This is substantially better than standard of care, which is currently at 2.4 hours. Substantial symptom relief, we've seen other standard of care at around 7, 8, 9 hours. Our 2.5-hour for this, we feel, is not only numerically important but also clinically relevant. Complete symptom resolution of 10.6 hours. It means that the median participants in our open-label Phase II study were symptom-free in less than 12 hours. Importantly, the single-dose resolution that we saw is going to be very key for our negotiations, not only with the FDA but also with payers, for the ability to have a single pill that completely resolves your attack. We also see that deucrictibant is presenting placebo-like tolerability, which is important, especially in small molecules. We received a thorough QT waiver earlier this year. We are very pleased with the way that the safety profile is turning out.
We hope to confirm that in Phase III. This is our Phase III study design. It's a crossover design. We have a single dose at 20 milligrams. Once again, this is the immediate-release. You have a very rapid uptick of drug in the system to achieve therapeutic threshold. Top-line data anticipated in the fourth quarter of 2025. Here are some of the endpoints that we're also looking at. We have guided the on-demand program, once we hopefully confirm our Phase II data in our Phase III, to file for an NDA in the first half of 2026. Moving on to the prophylactic program, we are measuring one extended-release tablet at 40 mg a day, and then people are able to roll over to the open-label extension. We are enrolling that right now and have currently guided towards data anticipated in the second half of 2026.
Important endpoints in our Phase II study that I've put out here on this slide include 85% reduction in overall attacks. This is at injectable levels. There are other orals that are approved, and we are aiming to not only own the oral class if we're able to confirm our Phase II in Phase III, but also really compete with the injectables and potentially outperform them. Our open-label extension data shows that we had a 93% attack reduction, which is, once again, not only numerically important but also clinically relevant in the competitive space. Once again, in the prophylactic program, we see placebo-like tolerability. We're very pleased with a clean safety profile here. As I mentioned, in both programs that we're running right now, we're really aiming to have this injectable-like efficacy, placebo-like tolerability, and the convenience of an oral therapy.
We feel that that is a paradigm shift from what we're seeing in other programs. I really think that we have the potential to be a preferred option in both long-term prophylaxis and in on-demand. I'd mentioned briefly that we intend to have a broader label than just hereditary angioedema. Here on this very complicated slide, you can see that there's bradykinin-mediated angioedema, which includes not only the center pathway, which is calcineurin-driven, but also other ways that you can have excess of bradykinin in your system leading to angioedema, which is called hereditary angioedema with normal C1. This is not driven by a SERPING1 gene mutation but could be driven by other mutations in the system. We believe that by addressing the bottom of the pathway, we're going to be able to achieve efficacy and tolerability in a broader population than just hereditary angioedema types I and II.
That leads us to an investigator-initiated trial of our extended-release tablet in acquired angioedema patients. I'd like to highlight that this is a very small study. Only four patients were in this, and we can see that there was one person who had one attack on day two. Since then, all four patients have been attack-free for over 24 months. Based off of this data and our hypothesis that deucrictibant could be effective in acquired angioedema patients, we intend to initiate a Phase 3 pivotal study in acquired angioedema this year. We're going to start off with a prophylaxis arm. It's going to be the same intended commercial formulation as in our hereditary angioedema program and then move over to on-demand until hopefully we're able to submit for a filing.
The intention of this timing is to align the acquired angioedema prophylactic program with the readout of our hereditary angioedema prophylactic program with the opportunity to potentially have a label of bradykinin-mediated angioedema. We have orphan drug designation in Europe and the U.S. for this bradykinin-mediated angioedema. If we're able to have this broader patient population, we may be able to, or we hope to speak with regulators about priority review, which could speed up the review process for us. Currently, there are no approved therapies for acquired angioedema patients. There's a high unmet need. As I mentioned, HAE is a competitive space, but we believe that there is still an opportunity for improvements within the landscape. I'd like to highlight here that these are sales uptake curves in the U.S. only. This isn't European as well.
We believe that the best product when it comes to market can become a market leader. It's not necessarily the first product to market. I think you'll see here you've got some interesting curves on both the green side, which is the prophylactic side of Takhzyro that entered the market after both Cinryze and Haegarda, but offered people a compelling once-every-two-week dosing regimen as opposed to Haegarda, which is twice a week. Also interesting that we have seen very high uptake of Orladeyo. This really speaks to the unmet need in the oral space. Orladeyo doesn't have the injectable-like efficacy that we see from these other prophylactic programs, but clearly, people are willing to forego efficacy in support of having the convenience of a daily oral.
You'll see on the right-hand side the blue curves that Firazyr, though second to market after Kalbitor, clearly took market share until it went generic. Ruconest is also an interesting therapy here. It really shows that patient services and marketing are very compelling levers to pull within the HAE space. We believe that even with the entry of new approvals over the past summer, we had the approval of Enjaymo, Donnatal, and Ecallantide, that there's still favorable pricing within the U.S. This is just an example of where people are right now. We're going to need to have our Phase 3 data and obviously negotiate with payers and the FDA to see what sort of pricing makes sense best for deucrictibant. Because we will have one molecule with two formulations, we hope to have two different brands for that. We're in discussion right now with regulators on that.
Our intention is to hopefully launch our on-demand program first, demonstrate best in class in the on-demand program, transition people from the on-demand, and add in our prophylactic program. We hope to compete highly not only in the oral space but also with injectables and prophylaxis, and then leverage that dual portfolio to be able to expand beyond just hereditary angioedema. Thank you very much. Appreciate you all being here. Thanks.
Thank you so much, Maggie. Yes.
Great presentation. If anyone has any questions from the audience? A question from me. What's your threshold for defining injectable-like efficacy in your two studies?
Great question. Within the on-demand program, which is going to be reading out first, we hope to have our end of progression hit between 15 and 30 minutes. Our PGIC a little better. Once again, that's our primary endpoint of onset of symptom relief. We hope to have between 1 and 2 hours, substantial symptom relief in 2 to 3 hours, and complete symptom resolution in under 12 hours. We also hope to have 85% of our participants be able to achieve those efficacy thresholds with a single dose. On the prophylactic side, our long-term extension data is demonstrating that we could be in the 90% of attack reduction. We're also going to be using the extended-release formulation, which I put up that slide for the acquired angioedema patients that had no attacks.
We hope to be above our 85% that we saw in the Phase II and potentially even in the 90% for efficacy on prophylaxis.
Thank you. How important is being the only drug in development with the potential to be used across on-demand and prophylactic, seen as a differentiator for payer and physician adoption?
Great question. HAE is a threshold-driven disease. That means if you're on prophylaxis and you somehow fall below that therapeutic threshold, we believe that what you could do is take an on-demand rapid uptake immediate-release capsule, get you back above threshold quickly. The idea would be to use both the on-demand and the prophylactic in concert together. Hopefully, we're going to show that our prophylaxis has no breakthroughs. We will see what we do with that. The ability to be able to have people decide what type of therapy they want to take, whether that is that they're on prophylaxis and then maybe their life changes, they want to come off of prophylaxis and then just treat on-demand. We really are agnostic to the way that the market breaks down between on-demand and prophylaxis because we have opportunities for patients to have an effective therapy in either setting.
It's also compelling from a payer negotiation standpoint. Certainly, once we have our sales and marketing team, it helps to have one person who can go into a physician or a payer and speak about two products. Definitely some complementarity there.
One last question from me. How large do you think the HAE population with normal C1 could be if diagnosed properly using your biomarker?
Yeah, great question. I put up that schematic slide, which is quite complicated. We think that normal C1 could be an additional 20% on top of the current HAE types I and II population. As you mentioned, Arabella, we have a biomarker that not only could help in the identification of normal C1 patients but also patients with acquired angioedema and HAE of unknown mutations. Looking forward to being able to explore those different opportunities for deucrictibant.
Thank you so much again.
Thank you.