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

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 treatment for rare diseases like Duchenne muscular dystrophy from March 2010 through its IPO on NASDAQ in 2013, and until its acquisition by BioMarin Pharmaceuticals 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. The company brings together executives with a breadth of expertise across pharmaceutical development and rare disorders, including HAE. And I'm looking forward to Berndt's presentation. The company has also quite recently IPO-ed on NASDAQ, raised over $300 million relatively recently and has achieved close to USD 1 billion market cap, and all this in a relatively short period of time. So with that further ado, Berndt, welcome you to the floor, and it's yours.

Yes. Thanks, Chris, and welcome, everyone, and thank you for attending the presentation. So you have to show this, as a public company now, the forward-looking statements and disclaimer regarding that. And I'm sure you've surely seen that many times. So I'd like to give you -- before we begin here, an overview of Pharvaris, to keep the highlights of the company. We focused on the therapeutic area of hereditary angioedema, which is a rare disease indication. It's currently a large global market of around $2 billion plus in revenues. It continues with a robust growth potential because the HAE patients are still looking to improve how they manage their disease, and that makes it interesting as a rare disease markets because it's, on the one hand, is established, but also with a very strong growth potential. We addressed that with an orally available small molecule targeting the B2 receptor pathway. It's a proven target. There are over decades of experience with the pathway with icatibant acute treatment of HAE, which is the target that the team at Pharvaris also developed at a prior company Jerini. We have a favorable PK/PD profile in 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. And the team that you see here on the next slide. In addition to myself, Jochen Knolle is the CSO. Jochen and I worked together at Jerini. And Jochen is my mentor of icatibant for acute treatment of HAE. And also recently, Peng Lu who joined us from Takeda/Shire a year ago. And it sounds not recently, but it's a year ago. And she was part of the global program lead for TAKHZYRO lanadelumab, which is our 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 in the API. 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 of 121, just call 416. And that study has already started, the Phase II study. And then 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 safety data in the Phase II study expected to start this year. And then for the prophylactic product, this is 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 with prophylactic treatment. And then we also have -- or stay still -- are still undisclosed programs in other B2-related indications. And 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. And it's also a potentially life-threatening condition if the swellings occur in the larynx, it could lead to suffocation. The attacks are completely unpredictable in frequency, location and timing and severity. It's not fully understood, but causes it, so adds to the excited level in a lot of HAE patients they have -- when they've been waiting for the next attack, not knowing when that's going to come and how severe it will be if it's [indiscernible]

Interrupting. But would you mind just putting into full screen, it's a little bit hard for us to...

Sure, sure, sure. I'll deal with that. Is that better, yes? So if left untreated, an attack last multiple days. They're commonly painful and could lead to hospitalization and multiple sick days. The prevalence is around 1:10,000 to 1:50,000. Translates to around 6,600 patients in the U.S. and around 8,900 patients in Europe. And there's still globally a large undiagnosed population in HAE. The medium -- the attack frequency you see here on the right is around 14 attacks per year, but it is very, very -- there are 15 patients. And the most patients have somewhere between 12 to 24 attacks per year. The mechanism behind HAE is an uncontrolled release of bradykinin. And our molecule PHA121 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. And that is what causes the angioedema or the swelling in HAE patients. And the current approaching is for HAE or either for on-demand or prevention for prophylaxis. And our approaches are plasma kallikrein inhibition further up in the cascade. All products, except one very recent, is -- are injectable. There's only one oral product recently approved. And the current therapies are efficacious, but they often have injection site reactions and the leave patients to delay treatment and then also to risk attacks, it's time-consuming, et cetera. So it's a big unmet need related to HAE patients to find better treatment options and an oral HAE patients in our experience and we are looking for. Icatibant is also an injectable. It's also bradykinin B2 receptor and it's a predominant therapy for treatment of acute attacks. And 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 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, PHA121, as I mentioned, that completed the Phase I SAD and single ascending dose and multiple ascending dose trials. And to date, in those studies, they've been well tolerated with no severe adverse events. And it has very viable, very favorable profile so far. So -- and also, no clear differences in adverse events between different dosing regimens versus placebo. And no significant changes clinically in the ECG safety lab assessments and so on. So favorable profile from a safety perspective so far. And PHA121 also has a very attractive PK profile, is its dose proportional and it's with single or multiple oral administrations. You see here the PK in multiple doses from 1 milligram to 40 milligram, in a linear fashion dose dependent and dose that has a rapid exposure. The uptake is extremely fast. It's delayed slightly with food. The Tmax is about 2 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 and -- but the uptake at about expected therapeutic levels is extremely fast. So there's no impact on food in that regard. The half-life is longer than icatibant. It's about 3 -- almost threefold longer than icatibant. And the MAD data also shows that you reach a steady-state exposure relatively quickly in the 72 hours, which is also a potential advantage also in the prophylactic setting, you could be more flexible to go on and off the prophylactic, so you don't need to build up over a week or 2 weeks. With PHA121, we have done the bradykinin challenge study to look at the -- comparing it to a study that was done with icatibant to come up with the right dose. With icatibant, it's many years ago also reviewed by the FDA. And that is -- in that bradykinin challenge study, we look at the effect of the molecule in inhibiting the clinical effects of the bradykinin administration. And the single dose of PHA121 is expected to have a similar PK pharmacodynamic effect as 2 injections of icatibant. So that you can see here at the bar on the graph on the left, the top graph on PK is very -- the exposure is less because the potency is much, much higher than icatibant, but the PD effect is expected to have longer duration than the icatibant. And then products that's like 416 and 719, these were prior to representations. So what we're looking for here. The sub capsule formulation past onset is important for on-demand and a reasonable duration to cover the attack. And -- but on the prophylactic side, of course, the uptick is the speed that I think it's less important, but you want to have a longer duration to maintain about 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 the plan of 3 different doses, and we plan to in that study to evaluate and soon to review within 4 hours in acute attacks and patients with HAE Type 1 or 2. It's also -- patients are also -- they are all controlled in this study. So each patient will -- treat three attacks to the drug and one with placebo. The primary endpoint is the VAS for our post-dose symptom relief and around 54 patients in this study. And the nice thing about HAE, and specifically also in this case that we expect that the study design and the primary endpoint is this validated in hereditary angioedema also from a regulatory perspective. On the prophylactic side, we will enter the prophylactic study. Also this year, initially with 416 to maintain momentum while we are in parallel developing our extended-release tablet 719. And the primary objective of that Phase II study, prophylactic is to assess safety and also get initial efficacy data. And then we will do a -- start a Phase I study then with the extended release formulation to bridge for 416, and we anticipate then that 719 will be included in the pivotal trial. We have initial data, and now looking at the PK/PD effect based on derived from bradykinin challenge that suggests that the PHA121 can reach exposure 4.5x over EC50 with the twice-daily dosing based on the current formulation, the 416. And the 4.5x EC50 is -- translates to comparable to the current exir of 87% attack reduction. Then on the financial highlight of Pharvaris to wrap it up. As Chris mentioned in the beginning, we are well financed. We raised $353 million capital since the inception of the company 5 years ago. And in fact, the $310 million of that was raised in the last 9 months. And we did our IPO on NASDAQ on February 5. And 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. And maybe I'll do the honors. It's -- so it's quite an achievement in 5 years, $1 billion 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 2 years, 5 years from now?

Well, our strategy is really to focus on bringing our HAE prophylactic on-demand to patients as fast and effectively as we possibly can. And so that's really the core focus of the company at this point. And then we also have looking -- starting to look into other opportunities related to the B2 mechanism to evolve. 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. And particularly as a small company to focus, of course, is to prioritize our HAE program, which we've 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.

Yes, that'd be great. Thanks a lot.