Joining us now is Berndt Modig, CEO of Pharvaris. Mr. Modig is a co-founder of the company and has served as chief executive officer since inception. He is also a director, and prior to co-founding the company, Mr. Modig served as chief financial officer of Prosensa Holding, a biopharmaceutical company focused on novel RNA modulating treatments for rare diseases like Duchenne muscular dystrophy from March 2010 through its IPO on Nasdaq in 2013, and until its acquisition by BioMarin Pharmaceutical in January 2015. Pharvaris is a clinical stage company focused on bringing oral bradykinin B2 receptor antagonists to patients. By targeting this clinically proven therapeutic target with novel small molecules, the Pharvaris team is advancing new alternatives to injected therapies for all subtypes of HAE and other bradykinin-mediated diseases. Company brings together executives with a breadth of expertise across pharmaceutical development and rare disorders, including HAE.
I'm looking forward to Berndt's presentation. The company has also quite recently IPO'd on Nasdaq, raised over $300 million relatively recently, and has achieved close to a $1 billion market cap, and all this in a relatively short period of time. Without further ado, Berndt, welcome you to the floor, and it's yours.
Yeah. Thanks, Chris, and welcome everyone, and thanks for attending the presentation. Let's see here. You have to show this as a public company now, the forward-looking statements and disclaimer regarding that. I'm sure you've seen that many times. I'd like to give you, before we dig in here, an overview of Pharvaris, the key highlights of the company. We focus on a therapeutic area, hereditary angioedema, which is a rare disease indication. It's currently a large global market with around EUR 2 billion+ in revenues. It continues with a robust growth potential because HAE patients are still looking to improve how they manage their disease. That makes it interesting as a rare disease market because it's on the one hand it's established, but also with a very strong growth potential. We address that with an orally available small molecule targeting the B2 receptor pathway.
It's a proven target. There are over decades of experience with that pathway with ecallantide for acute treatment of HAE, which is the drug that the team gives at Pharvaris, also developed at a prior company, Dyax Corp. We have a favorable PK/PD profile. This molecule that makes it suitable for both prophylactic and on-demand treatments. That's the company's strategy, to develop for both the full spectrum of HAE and there are also potential opportunities for expansion into other bradykinin-mediated diseases. The scientific expertise centers around that pathway and our knowledge and expertise about the B2 receptor. The team that you see here on the next slide, in addition to myself, Jochen Knolle is the CCO. Jochen and I worked together at Dyax Corp, and Jochen is the inventor of ecallantide for acute treatment of HAE.
Also recently, Peng Lu joined us from Takeda, Shire, a year ago, and it sounds recently, but it's a year ago. She was part of the global program lead for TAKHZYRO, lanadelumab, which is a product for prophylactic treatment of HAE. This is an overview of our pipeline in our B2 receptor mechanism, and we have concluded our phase I work with PHA121 . That's our basic molecule, the API. We completed phase I in MAD, and we have just very recently started the on-demand study for using a small capsule formulation of our same API, PHA121 . That's called PHVS416. That study has already started, the phase II study.
We also plan to start the prophylactic study in hereditary angioedema, also using initially the small capsule formulation, to get the initial efficacy data and further safety data in a phase II study expected to start this year. For the prophylactic product, it's the 719. That's an extended release tablet formulation that we are developing, and we will conduct a phase I study start this year. The bridging study then to ultimately then use 719 in the registration phase for prophylactic treatment. We also have, are still undisclosed programs in other B2-related indications. We have exclusive rights to everything in our pipeline at this point. Hereditary angioedema is a rare disease, as I mentioned, it's a genetic lifelong condition characterized by attacks of swelling. It's also a potentially life-threatening condition.
If these swellings occur in the larynx, it can lead to suffocation. The attacks are completely unpredictable in frequency, location, and timing, and severity. It's not fully understood what causes it, which adds to the anxiety level in a lot of HAE patients when they live waiting for the next attack, not knowing when that's going to come and how severe it will be. If it's left untreated.
Sorry.
Yeah.
Interrupting, but would you mind just putting it into full screen? It's a little bit hard for us to.
Oh, yeah. Sure. I forgot about that. Yeah.
Thank you very much.
Of course. Is that better? Yeah. If left untreated, an attack lasts multiple days. They're commonly painful and could lead to hospitalization and multiple sick days. The prevalence is around 1 to 10,000 to 1 to 50,000, translates to around 6,600 patients in the U.S. and around 8,900 patients in Europe. There's still globally a large undiagnosed population in HAE. The median attack frequency you see here on the right is around 14 attacks per year, but it could vary a lot between patients. Most patients have somewhere between 12 and 24 attacks per year. The mechanism behind HAE is an uncontrolled release of bradykinin, and our molecule deucrictibant is designed to block the signaling in bradykinin. Bradykinin binds to the B2 receptor ultimately in the cascade that you see here on the left.
That is what causes the angioedema or the swelling in the HAE patients. The current approved treatments for HAE are either on demand or for prevention, for prophylaxis. Other approaches are plasma kallikrein inhibition further up in the cascade. All products except one very recent are injectable. There's only one oral product recently approved. The current therapies are efficacious, but they often have injection site reactions and they lead patients to delay treatment and also to risk attacks. It's time-consuming, et cetera. It's a big unmet need with HAE patients to find better treatment options, and an oral is really what HAE patients in our experience are looking for. icatibant is also an injectable, but it's a bradykinin B2 receptor, and it's a predominant therapy for treatment of acute attacks.
In our view, addressing this at the end of the cascade has a lot of advantages and allows you to potentially also treat other forms of angioedema that are not related to the plasma kallikrein pathway. The need for an oral is very clear from what we see from also from KOLs and patients, and that is the next thing for what the patients are looking for, as you can see from the testimonials on this page. Our molecule, deucrictibant, as I mentioned, that completed the phase I SAD in single ascending dose and multiple ascending dose trials. To date, in those studies, they've been well-tolerated, no severe adverse events, and it has a very mild, very favorable profile so far.
And also no clear differences in adverse events between different dosing regimens versus placebo, and no significant changes clinically in ECG safety lab assessments and so on. A mild, favorable profile from a safety perspective so far. Deucrictibant also has a very attractive PK profile. It's dose proportional, and with single or multiple oral administrations. You see here the PK in multiple doses from one milligram to 40 milligram in a linear fashion, dose dependent, and it also has a rapid exposure. The uptake is extremely fast. It's delayed slightly with food. The Tmax about two hours, but that has no impact on the therapeutic significant. You see on the curve to the right, the difference between fed and fasted, and the food effect reduces the Tmax. It extends the duration, but the uptake above expected therapeutic levels is extremely fast.
There's no impact on food in that regard. The half-life is longer than icatibant. It's about almost threefold longer than icatibant. The MAD data also shows that you reach a steady state exposure relatively quickly, within 72 hours, which is also a potential advantage. Also in a prophylactic setting, you can be more flexible to go on and off the prophylactic therapy. You don't need to build up over a week or two weeks. With PHA121, we have done a bradykinin challenge study to look at comparing it to a study that was done with icatibant to come up with the right dose with icatibant that many years ago also was reviewed by the FDA. In that bradykinin challenge study, we look at the effect of the molecule in inhibiting the clinical effects of a bradykinin administration.
A single dose of PHA121 is expected to have a similar PK/PD effect as two injections of icatibant. As you can see here at the bottom, the graph on the left. The top graph on PK, the exposure is less because the potency is much, much higher than icatibant but the PD effect is expected to have longer duration than icatibant. On the products PHVS416 and PHVS719, these are cartoon representations of what you're looking for here. On the soft capsule formulation, a fast onset is important for on-demand and with a reasonable duration to cover the attack. A bit on the prophylactic side, of course, the speed of the uptake is less important and you want to have longer duration to maintain above therapeutic plasma target levels. Our phase II study in on-demand is already underway.
This is an overview of the study design. We started it. This is planned at three different doses and we plan in that study to evaluate the symptom relief within four hours in acute attacks in patients with HAE type 1 or 2. Patients are also controlled in this study, so each patient will treat three attacks, two with drug and one with placebo. The primary endpoint is the VAS 4-Hour Post-Dose Symptom Relief and around 54 patients in the study. The nice thing about HAE, specifically also in this case, we expect that the study design and the primary endpoint is validated in hereditary angioedema also from a regulatory perspective. On the prophylactic side, we will enter the prophylactic study also this year. Initially with PHVS416 to maintain momentum while we are in parallel developing our extended-release tablets, PHVS719.
The primary objective of that phase II study prophylactic is to assess safety and also get initial efficacy data. We will do a start of phase I study then with the extended-release formulation to the bridge for PHVS416, and we anticipate then that PHVS719 will be included in the pivotal trial. We have initial data looking at the PK/PD effect derived from the bradykinin challenge that suggests that deucrictibant can reach exposure 4.5 times EC50 with the twice-daily dosing based on the current formulation, the PHVS416. The 4.5 times EC50 translates to comparable to the current TAKHZYRO 87% attack reduction. On the financial highlights, corporate highlights to wrap it up. As Chris mentioned in the beginning, we are well-financed. We raised EUR 353 million capital since the inception of the company five years ago.
In fact, EUR 310 million of that was raised in the last nine months. We did our IPO on Nasdaq on February 5th. That wraps up our presentation. It's a quick flyby but open for some questions.
Great. Thanks, Berndt. I think we have time for one question. Maybe I'll do the honors. It's quite an achievement, five years, a billion-dollar market cap, Nasdaq listing. The product seems quite well-differentiated and there's clearly an unmet need for that. What's the next steps for the company, just in your vision, you have the dry powder, so to speak. Where do you go in two years, five years from now?
Our strategy is really to focus on bringing our HAE prophylactic and on-demand to patients as fast and effectively as we possibly can. That's really the core focus of the company at this point. We also have starting to look into other opportunities related to the B2 mechanism. It's a little premature to talk about specifics there today but in due course, we will also inform a bit more about what we're going to do there. As a small company, the focus, of course, is to prioritize our HAE program which we built to bring an oral therapy for HAE patients that we believe is a great unmet need for this patient community.
Great. Well, thanks, Berndt. We wish you luck with that and we'll be following Pharvaris.
Yeah. Doing great. Thanks a lot