If you have any questions, please reach out to your Morgan Stanley sales representative. I'd like to introduce Pharvaris. Very happy to have the team here: Berndt A. Modig, CEO, David Nasip, CFO. Welcome. Thank you very much for attending this year. To kick things off, could you set the stage by walking us through deucrictibant's value proposition across both acute and prophylactic treatment of hereditary angioedema?
Yeah, thanks, Max. Great to be here again. So, deucrictibant, being an oral therapy option, fills a very specific unmet need in the space. We've seen over the years, and that's a key feature, of course, the oral aspect of it. You expect that the oral segment and the desire and the preference for oral in the patient community is very high, and to have a bit more convenient therapy that allows function and normalcy in patients' lives. It starts with oral, but it doesn't stop there, of course. The paramount proposition for any therapy, and especially in HAE, is efficacy. To have an oral in combination with a high efficacy, we describe it as injectable-like efficacy and based on the current therapies and the efficacy level that we see there. To have that in combination with an oral is one of the key propositions.
Of course, given that this is a lifelong treatment, also a placebo-like tolerability and something that is not a big burden on patients and the side effects profile is also, of course, key. It's all about these three pillars, you could say. Currently, today, in our view, there is no therapy out there today that really meets all those three requirements fully.
Okay, that's great. Hereditary angioedema, it's an exciting space. A lot of new players and therapies are becoming available. Can you share your perspective on the evolving HAE market, particularly trends in treatment adoption, and maybe talk to the incidence or prevalence rates in the U.S. and the mix between on-demand and prophylactic treatment?
Yeah, so in recent years, I mean, of course, the prophylactic segment has grown and has been established primarily also with the introduction of injectables with a relatively low injection frequency like Orladeyo. The guidelines for treatment in this patient's, in HAE, is to maintain as much as possible freedom from attacks and have as low attack rate as possible. The growth in the prophylactic segment that we see continues. I think it's about 67% in terms of the population today and growing, and about 80% in terms of the value in the prophylactic segment. Having said that, I think also the on-demand segment is also very viable in our view. It's a different way of treating. It has to have some flexibility that the prophylactic doesn't have, especially if you're on the longer-acting injectable, you have your drug in your system a very long time.
The innovation in the on-demand space, it's also important that we haven't seen that to the same degree in the last decade. An efficacious oral therapy also for on-demand, we think is also a very viable proposition.
Okay. There was a competitor in the on-demand space that recently launched. What I think is interesting from a competitive perspective is deucrictibant based on two different formulations. You're able to potentially address both the prophylactic and on-demand. Can you potentially, could you talk to that dynamic?
Yeah, I mean, that is the, as also we say in our corporate presentation, science for patient choice. I mean, I think the decision how to manage the condition in hereditary angioedema (HAE) is a very individual decision and what your preference is and what your daily circumstances are. It's not just calculating the number of attacks. It's about how the patient feels about the attack and what is the anxiety level of going through an attack and the unpredictability. That all drives the decision whether the patient wants to be on prophylactic or on-demand. I think having the same active ingredient in two formulations gives us a clear differentiation in the space. Also, newly diagnosed patients typically start out with therapy in adolescent years. An on-demand therapy might be practical for that patient population. As they continue and sometimes typically you see attack frequency goes up over the years.
If the patient is comfortable with deucrictibant in one form, they can also then go over to prophylactic and have that maintain the comfort that they then could have potentially with one drug.
Okay. Based on your market research and talking to KOLs, what is their view on having two different formulations but one option potentially?
I mean, they generally have perceived very well. I think that that's a default code. Sometimes people ask about if there's any sort of mechanistic differentiation there in terms of treating a breakthrough attack with the same compound. From a mechanistic perspective, there is not, there's no difference. There's no specific rationale to use a certain drug in prophylactic and then another one to treat a breakthrough attack. You could, because it's all about maintaining the plasma exposure level that's associated with therapeutic efficacy. That's just not unique to deucrictibant. That's true also for the other therapies.
Okay. Before we dive into the data, maybe just refresh our memory in regards to the mechanism of action, how it differs from the competitive approaches, bradykinin in general.
Yeah, we are the only company out there with, as you mentioned, a formulation both for prophylactic and on-demand with the bradykinin B2 receptor antagonist. When we started out with Pharvaris, my co-founder is an inventor of the deucrictibant. We have a very deep understanding about the pathway and that receptor. We've seen the efficacy that's been able to be achieved with radical inhibition at the end of the cascade. It also has the advantage and the potential advantage to treat other subtypes of angioedema, not just the type 1 and 2. For example, patients with other mutations and so on, so normal C1, it's called a plasminogen, and then have the overproduction of radicals and have the same clinical manifestations as type 1 and 2, but it's a very different pathway. It bypasses this kallikrein. It's kallikrein independent.
That being at the end of the cascade with bradykinin B2 receptor antagonist provides a mechanistic advantage.
That's an important point. Moving on to on-demand, you recently moved the RAPIDe-3 Phase 3 readout up to the fourth quarter of 2025. I believe it was initially you were guiding to the first quarter. Before we look ahead, could you walk us through the key efficacy and safety data reported to date and what underpins your confidence in this readout?
Yeah, we were very excited when we saw the Phase 2 data, of course. I mean, the benchmark so far had been the efficacy level of berotralstat. I think that deucrictibant, based on the data that we saw in the Phase 2, is, of course, the onset of symptom relief, which is the primary endpoint. That's a key parameter. It doesn't stop there. It's really also about the completion of the resolution of the attack, the need for a second dose. On those parameters, the Phase 2 data and deucrictibant show a clear differentiation both against berotralstat as well as against the other therapies that we've seen for on-demand. That is something that we, of course, hope to see similar data in our Phase 3 study.
Okay. That's very helpful. I think basically in your corporate deck, you do a great job kind of laying out the competitive landscape, what other options, both injectable and oral, are out there. Maybe we can drill down just a bit on key data points. You highlighted qualitatively what you're looking for, but is there anything quantitatively we should keep in mind when the Phase 3 data comes out?
If you sort of look at the whole sequence from when the attack starts until the complete resolution, as I mentioned, it's important to really look at the totality of that because ultimately what the patient is looking for is a reliable resolution of the attack in a good timeframe, ideally with only one dose. In our trial, we also have a specific endpoint, one of the secondary endpoints called end of progression, which is unique to our trial, and that is even before onset of symptom relief. That's when the patient then starts to see that the attack is getting under control. The primary endpoint on the onset of symptom relief is important, but it's only the beginning. We also expect to see, based on what we've seen so far, that it's relatively similar compared to standards of care, compared to the other oral therapy.
Also, the deucrictibant is within the range of one to two hours. Where we then need to look further is, of course, the reduction of severity called FF50, and also the need for a second dose. I think there, based on the Phase 2 data, the deucrictibant has a meaningfully lower usage of second dose. Also, the number of attacks within 24 hours resolved with only one dose is also very different in the data. Those are the things to look for to really see the differentiation between the other therapies.
Do you think it's appropriate, or are you looking at it internally as trying to achieve injection-like efficacy or just compete against the other potential oral that is out there?
I think the Phase 2 data shows, we think, that the deucrictibant has overall better data than even the standard of care today, better than the berotralstat. That is also partly because we think because of the longer half-life, the lower need for a second dose. I think that the other oral therapy does not really meet the level of the current standard of care in injectable. It has the oral convenience, of course, but it doesn't have the, from what we can see, the efficacy. That's what we hope to provide that bring a meaningfully better efficacy.
Okay. That's very helpful. How are you aligning Phase 3 with label-relevant claims, payer expectations versus rivals? Will you pursue head-to-head or structured indirect comparison to make a differentiated claim at launch?
We're not directly planning to do any head-to-head at the moment, but it's something potentially at some point in the future. I think the differentiations will be also, of course, developed by the data as such and on the parameters that I mentioned. For example, in on-demand, I think the key thing of importance for payers is the resolution of attack with one dose. I think also from the patient perspective, that we think that that is a very significant difference because the anxiety of wondering if you're going to take a second dose or if they need a second dose or not, that adds to the complexity. To have the one resolution with one dose, I think, will be also an important aspect not only for patients but also for payers.
Before we move to prophylactic, can you just touch on again what drove the acceleration in timeline of moving up from the first quarter to the fourth quarter?
Yeah, when you start out the study, of course, the on-demand study, the first step is to complete the enrollment. After that, also concurrently collecting the database with the attacks. That went very quickly, a little bit faster than we had anticipated. We're excited about that. I think that also highlights the level of awareness about the program and the interest in patients participating in the trial. We completed the enrollment in 12 months. That was faster than the Phase 2. Now, based on our assessment of the database of attacks collected, etc., and the quality of attacks, the total assessment then provided us the comfort to update our guidance.
I'm assuming there's going to be inevitable cross-trial comparison. Is there anything you would call out, baseline characteristics, attack frequencies, just severity of the patients overall compared to your competitors that you'd like to highlight?
I think it would be very similar. I mean, what we have in our Phase 3 trial, we also allow for a smaller number of patients to be on a prophylactic treatment during the trial. We may see some attacks may be milder potentially. It's a minority number of patients that have controlled and limited who can be on prophylactic. I think that we still have the same criteria that we had in the Phase 2 trial in terms of attack frequency to be eligible to enroll and also to qualify the attack like we did in the Phase 2, but it contributed in the assessment of the treating physician, then the real attack and not just something else. All those parameters are the same as in Phase 3.
No major changes from the Phase 2 to the Phase 3?
No, I think that that is maybe the key change. I mean, of course, the general Phase 2, Phase 3 with more sites and all that, that's not unique to our Phase 2, Phase 3. That's typical for Phase 3 trials because they have a broader footprint. We also have a very small number of patients with normal C1 included in the trial, so you can collect data on those patients, and that could potentially support the expansion on the label of deucrictibant, which would be another differentiator.
Great. Pivoting to prophylaxis, with your pivotal CHAPTER-3 Phase 3 readout expected in the second half of 2026, could you recap the most important data you've shared so far that kind of frame expectations for this program?
I think, moving, switching gears to prophylactic, it's relatively more straightforward or simple in terms of both in terms of trial design and also in the endpoints. There, it's really measuring the reduction of attack compared to placebo. In our Phase 2 trial, we had about 87% attack reduction compared to placebo. That is clearly in the range of what we call an injectable-like efficacy. In combination with an oral, which I think, as I mentioned initially, is something a key differentiator for deucrictibant. Also, I think 49% of patients had zero attack rate compared to placebo. In our open-label extension, we had a further improvement of attack reduction to 93% and for reduction of severe attacks of 96%. The median attack rate was also to zero. Again, in the Phase 3 trial, we have 80 patients to be enrolled.
In the Phase 2 trial, it was about over 30 patients in three dose groups. Now we have 80 in Phase 3, 80 patients with one dose. It's clearly powered more for collecting safety database rather than powered for efficacy. It's very highly powered on the efficacy side.
Is there any chance we'll see this closer to the middle of the year, or are we going to keep guidance around the second half?
Right now, the guidance is maintained in the second half, and the enrollment is on track. We had sometimes in some sites, especially in Europe, we see a slowdown in the summer period, but we actually didn't see that. We were happy about that. Things are on track. Once we get more visibility on the enrollment completion, we may provide more precision in the guidance. Right now, it's still the second half of it.
Okay. Maybe you can talk about the potential patient profile because there are a lot of competitors in this space, different modalities that are being investigated. Is there a specific attack phenotype or patient segment you think deucrictibant would address that others won't?
I think it's starting with newly diagnosed patients. I think we see the preference for an oral, and it's very logical then to possibly start out with an oral therapy once you have your first diagnosis. We see 150 to 300 new patients coming in every year. If you are able to provide the level of therapeutic satisfaction to these patients, then they presumably would stay. The switching that you see in the HAE space and continue to see is really driven by the lack of satisfaction that patients are still looking for something that works better. I think about 67% of patients, based on a survey, feel they are still not satisfied with the treatment. They're looking for something better. First-line oral with a highly efficacious oral, I think, would be a key factor.
I think also in the younger population within the on-demand, it's also the patient segment that can then benefit. I think the overall availability of portability of a convenient oral is that many patients today just don't take care of their therapy with them. A lot of attacks that don't still go untreated.
Okay. Talking more broadly, given that there are two oral options on the market for prophylactic and on-demand, what learnings would you take from the experience for these companies launching their drugs? Thinking about prior authorization, the payer dynamic, pricing, I know it's too early, but anything you could provide around that would be helpful.
No, I mean, I think our competition has done a very good job in launching from what we can see. I think it also highlights the really high unmet need for an oral. I think that in combination with the search for even for good efficacy also in an oral, I think makes us excited and optimistic about the deucrictibant. I think on the payer side, there has been no real sort of drastic changes in the pricing landscape. I don't think in there because with the new therapies, different companies seem to maintain the current structure.
I think on the on-demand side, again, the best track attack resolution with only a single dose, it will be a key differentiator in the eyes of the payers because to really know what the attacks that you have to treat, a lot of attacks with the second dose, and you have uncertainty there and the lack of maybe control in the eyes of the payer out of patients who are using the different one dose or two doses, etc., adds complexity. I think from the payer perspective, the attractiveness of single dose resolution is important.
Okay. Pivoting, I believe the FDA accepted the TQT waivers for both formulations. I think this is important overall based on how it differentiates you from the prophylactic option on the market. Could you speak to the advantages in regards to milestones or cost and time overall?
The milestones of?
Just talk about because we won't have to run an additional study.
Oh, I see. Okay. Yeah. Yeah, yeah. Yeah, of course. I mean, that is what enables us to have the timeline guidance that we have now. We had provided the full non-clinical and clinical data and assays and modeling and all of the totality of that assessment. That is why the FDA gave us that waiver. We were happy about that, of course. I think that is also another differentiator that we think of the deucrictibant.
Because Orladeyo did not.
One of the many differentiators.
Yeah, yeah. Orladeyo was not granted that same waiver, correct? Because at higher doses, I believe it has some potential issues there. Okay. Moving on, maybe you can just talk about the next, I mean, it's going to be an exciting next 6 to 12 months, but what should we keep an eye out for in regards to milestones, catalysts, how is CMC manufacturing going, and any predicted regulatory interactions?
Yeah, so the completion of the Phase 3 top line data then in Q4 on-demand, and then we would then work hard to get the filing done as quickly as possible. I'm now gathered in the first half of 2027, and we look forward to the data readout in the second half of next year for the prophylactic. That will follow the same filing as well. We also expect to, so we have to see based on those timelines and if they work out as we anticipate, then potential launches in the first half of 2027 and the first half of 2028, both for on-demand and prophylactic respectively. We also have initiating a trial in acquired angioedema later this year, and that is with the aim also to get the label in for that indication.
If we are successful in that, we're to get a broad label for deucrictibant in what's called bradykinin-mediated angioedema, not just type 1 and type 2. If the timing works there, we together with the prophylactic data, then to potentially file all that together with the NDA for the prophylactic data. That is, of course, subject to completion of that study in time.
Okay. I believe there's an investigator-initiated study that provided the supporting data to move into other indications. Can you talk about the data to date, what the opportunity looks like?
Yeah, correct. There's an investigator-initiated study that's been conducted both in on-demand and prophylactic, and also using the extended-release formulation, by the way, in a small number of patients, only four patients. These are patients with acquired angioedema that typically then use a C1-inhibitor off-label. They're investigated in deucrictibant in the prophylactic setting with the XR tablet. We've seen, except for one attack in the first day or two with one patient, all four patients have been attack-free now for almost 18 months. That's very encouraging, not just for the indication of acquired angioedema, which follows the same pathway. It's also a reproduction of bradykinin-mediated through the kallikrein pathway. It is, of course, also gives us additional insight into how the XR formulation works in the prophylactic setting.
What is the relative market opportunity there compared to HAE?
For right now, these are patients that are referred by other physicians to HAE treating physicians because they experience these attacks. If they are suspected or diagnosed as bradykinin-mediated angioedema, they get the treatment. That's about 10% of the type 1 and 2 today. These are patients that are treated by other physicians, and possibly, the level of awareness is not as high. Once there is a drug or with a label for that indication, it enables us also to increase and work on that segment of the market to potentially increase that even further.
Great. Maybe I'll ask one question for David in regards to financials. I believe you reported around $200 million in cash, cash equivalents, at the end of 2Q. You recently raised, extending the runway to the first half of 2027. How are you prioritizing capital allocation across pivotal trials, commercial buildout, and thinking about potential BD opportunities?
Sure. The guidance of cash runway into the first half of 2027 assumes the completion of the on-demand, prophylactic, and AAE studies, and also the filing for ODT and prophylactic. It also assumes the buildout of our U.S. sales and marketing infrastructure will probably be at around 80 people by the end of 2026 and maybe 90 by the end of 2027. We're adding a few more for prophylaxis. All that's baked into that H1 2027. We do have an active BD effort. The guiding criterion for doing a deal is, can a partner or a distributor do a better job directly outside the U.S. than we can? Obviously, it could also result in some upfront or milestone payments that might be helpful.
At this point, given how close we are to Phase 3 data, approval or filing and approval, we have a whole array of non-dilutive opportunities available to us from debt to royalty to other kinds of structured finance, all of which get easier and less expensive as you get closer to launch. We're in very good shape from that perspective.
Great. Pivoting to a couple of survey questions that we've been asking on our covered companies. With China's rise in biotech innovation, how are you thinking about your competitive position here? Will this influence your R&D or BD strategy?
Right now, of course, there's a lot of innovation coming from China. We're watching that closely, but there's nothing that has a really immediate impact on us at this point in time. For Pharvaris, it's also thinking about what could be the next product after deucrictibant. Looking at what can be built in-house or what can be sourced outside, etc. China, of course, and all the innovation comes there. That is conceivably something that you can look at at some point. In terms of our commercial opportunity in China, that's also a market for HAE that's significant. It's, of course, as everybody knows, a complex territory. Most likely for a company our size, they would be working with a partner. It's definitely an opportunity that we think is worthwhile exploring.
How are you currently leveraging AI or thinking about AI's future disruption potential?
Yeah, we are. I mean, like most other companies, I imagine, are looking into AI. We have a sort of pilot in-house where we're looking at the use of a proprietary sort of AI platform or model, not meaning that it's not data that goes into the public domain. Something that's sort of in-house to use for medical writing to support data analysis, etc. We have not really looked at AI at this point as a way to reduce the number of employees or anything like that. I think that we're looking at it as a tool to support it, to support some processes maybe, and also generate writing and things like that. There's lots more you can do with AI in the pharma setting, of course, also at the commercial stage. We're looking into that also in the future and making projections and forecasts and things like that.
Interesting. Okay, last question. What has been most impactful from the regulatory side? Would you say it's the FDA, MFN, or tariffs?
I'd like to say that, I mean, everybody asks this, and I think every company gets the same question these days. How is the interaction with the FDA? We have very positive interactions with the FDA. We found the people that we deal with at the FDA to be extremely supportive and constructive. We have nothing but good things to say about that. On tariffs, being an international company, that's something we're obviously looking into and also looking at potential mitigation strategies there within the legal framework. It's something that we are not overly concerned about. I think we have some flexibilities there. It's also something that the whole landscape might change in the future as well. There are a lot of things going on in that topic, as we all know. The same is for M&F.
That's something that, watching that as a small company, the influence doing that, I think it's hard for us as a small company to do. I think that there's a lot of attention to that topic. How that will shake out in the future, we'll have to see.
Thank you very much for your time. Appreciate it.
Great. Thanks, Max. You too.