Pharvaris N.V. (PHVS) May 20, 2026 Conference Transcript

All righty. Hi, everybody. Thank you for joining us for this next session. My name is Nevin Varghese. I'm one of the biotech analysts here at RBC Capital Markets, joined on stage by Farveris and the head of IR there, Maggie Beller. Maggie, thank you so much for being here with us.

Thanks, Devin. Thanks for having us.

Of course. So let's get into it. I think I'd love to start with the recent pivotal data that we saw from the RAPID-E3 trial of do you correct to bend IR, where we saw significant on-demand efficacy in acute HAE attacks.

I'm curious, since the data and as you've been doing more market research, what specific endpoints that you've seen resonating most with clinicians and patients uh whether that be the time to symptom relief or tax sobriety reductions um or or the time to end the progression um yeah uh before i start off i just want to remind everybody that i'm going to be making forward-looking statements for full disclosures um we were really excited to put out our data in december of last year for repeat three one of the things that is uh especially important about this decreed event data is that um in addition to hitting our primary endpoint, which was time to symptom relief of a little better, in 1.28 hours. We also hit all 11 key secondary endpoints with statistical significance in a hierarchical fashion. As you mentioned, Nevin, there are a bunch of endpoints within that, and the full attack trajectory is an important aspect of addressing HAE attacks. So end of progression in 17 and a half minutes is a very important psychological endpoint for patients. This is the first time that they stop feeling worse in their attack. Basically that means that they know that the medicine is working again. So a really quick endpoint there is important. We of course have our primary endpoint of 1.28 hours. As you mentioned, another key important endpoint here is time to complete symptom resolution. So Ducrectivant showed that in a little less than 12 hours we're able to have no symptoms anymore. This is incredibly important. That means that you can basically take Ducrectivant at night when you start to feel an attack coming on. By the time you wake up in the morning your symptoms are gone. The last really important endpoint here is our single dose resolution. 83% of attacks treated were addressed with a single dose of Ducrectivant. This is important not only for the patient experience, but also when we start to communicate with payers about how many doses it takes to completely treat an attack.

How do you see, you know, perhaps some of these endpoints potentially changing in a real-world scenario as well? So as, you know, were we seeing different data in the pivotal as we, like, how is that kind of related to what we've seen in the open label extension data? And then how do some of these endpoints that we've seen compare to some of the other competitive entrants that we've seen, too, from one from Calvista's sub-trial set, which is already commercial, and also from the generic catamount as well?

Absolutely. In our phase three study, we intentionally designed the study to evaluate the efficacy of decryctivant in HAE attacks. So we actually asked people to confirm that they were having an HAE attack with their investigator. So with that, inherently, you have some delay to treatment. One of the things that we are seeing in our open label extension is there's a lack of delay of treatment there. We would anticipate in real world people treating as soon as they start to feel symptoms, not waiting to confirm an attack. across the board anytime you treat an attack earlier you tend to have faster resolution so we may even see that in real world those times to to all of the endpoints end up being a little bit faster you end up having milder attacks if you're able to treat them faster so that's one thing that we're looking forward to in our open label data and also in in the real world evidence that we have with use of Decrectivant. With respect to comparison to standard of care and also the recently approved oral, I will highlight that there are no head-to-head studies right now. So really, we're just comparing numbers to numbers. So it's not exactly comparable. But one of the things that we were thrilled to see is that, once again, across the board, across all the endpoints, do crictobant numerically outperform standard of care, which is a catabant in most cases, as well as numerically is faster to time to initial symptom relief and complete symptom resolution than ectorly, which is the recently approved oral and the on-demand space.

Got it.

And then as you've been talking to patients and doctors, how has the how has the oral formulation resonated and what what takeaways have you have you have you derived from CalVista's recent launch and how that de-risk the commercial opportunity absolutely across the board both we CalVista and physicians agree that the oral entry in the acute market really is important because it decreases the treatment burden that you have that means that of the 70 percent of attacks that currently are treated there are still 30 percent that are not whether that's because people leave their their uh kataban at home they don't want to excuse themselves because they have to inject over a long period of time by having an oral that works you there there will be trust built in the fact that you can discreetly and quickly treat an attack we would anticipate that the number of attacks that are now left untreated would decrease because of that treatment burden decreases um we think that that's that's across the board so actually the number of attacks treated could increase i see yeah and just given that a lot of these attacks are mediated by stress

responses having the confidence of having an oral that you can take with you wherever you go could also potentially you know moderate the the severity of these attacks as well if they do occur um okay so i i know i know you guys have been hard at work on the nda filing i'm just wondering if we could get a status update on that um and if there's any you know consideration for looking at accelerated pathways to get this to market market sooner we're on track to file our nda in the first half of this year so uh no no update there but no news is good news on on our side on the first half so getting close we would expect to have a normal review period for that of course we would be pleasantly surprised if we received priority review but we haven't seen a priority review for other acute got it but let's talk about what the commercial launch could potentially look like i guess before we get into the commercial dynamics if you can talk a little bit about what the pre-commercial work that the company has been doing in order to prep for the launch of IR. And any learnings, again, that you've taken away from Calvisto's recent launch that you might be able to apply here to perhaps accelerate uptake of IR and how you see kind of the dynamics of that playing out as well with Ectorly on the market?

Yeah, I think that the Ectorly launch confirms that there is an unmet need for an oral. I think, frankly, they've done a great job with their launch, and we're hoping to see the same sort of adoption of Ducrictivant that Ectorly has seen. Some of the things that we've already been doing on our end, we've been building out our commercial infrastructure, so that includes making key hires. For us, we would anticipate our U.S. commercial infrastructure to be about 70 people for the IR launch. We'll probably add another 10 people to that when we hopefully launch in prophylaxis as well. Of that, about 30 to 40 people should be salespeople. So we can expect to have similar to other HV companies that commercial infrastructure in the United States. Some of the things that we're thinking about right now, not only in terms of segmentation of patients and also profiling of physicians for appropriate communication is also just raising the treatment expectations. Right now, people are needing to forego, whether it's efficacy, tolerability, or convenience, between their injectables. If they're, for example, taking CatBan, it works really well, but of course you sting yourself and you have to inject. It's not very convenient. There are some other trade-offs with respect to efficacy if you end up having the convenience of an oral therapy. So what we're trying to do right now is communicate to the market about raising those expectations and not allowing good to be good enough. We're hoping that Ducryctoban's label also reflects the fact that we believe that we have a highly effective, tolerable, and convenient therapy for on-demand. So those are some of the things that we're doing right now with respect to business state education and communication with the market. Then when we think about switching behavior, we really think about three main areas, right? You have the people who are on a catabant right now where they've either decided to remain on a catabant or they have switched to Ectoralee and then come back to a catabant. one of the things that we're really excited about is the ability to utilize the same mechanism of action for a catavan which is the widest used on demand therapy right now with like I said so not head-to-head potentially faster time to onset of symptom relief symptom resolution and single dose durability so same mechanism potentially improved efficacy and single people who trust that b2 receptor antagonism is the appropriate way to manage their hae can now have the same mechanism but with a potentially better option got it next is people who are on c1 replacement right now most of those patients tend to be normal c1 patients now you can as you may know hae type 1 and 2 are due to c1 inhibitor deficiency or dysfunction however normal c1 is results in excess bradykinin from other mutations, whether that's the asminogen mutation, kinogen mutation, angiopotent, factor 12, right? There are a bunch of other ways that you can have excess bradykinin. Because du-crictobant acts at the bottom of the cascade, we're able to address all of these patients regardless of where their excess bradykinin comes from. we believe that those normal c1 patients would would be ideal for a decretivant treatment and we have data from repeat three that show that normal c1 patients in both factor 12 and posminogen mutation uh the efficacy matched across ages type 1 and 2 and normal c1 so that's sort of the second area and then last we think about people who are on on the oral ectorly right now right is there an opportunity for them to have a single dose durability potentially faster time to onset of symptom relief complete symptom resolution like I said in 12 hours as opposed to over 24 hours for for ector relief and we think about that improved efficacy as as a key switch opportunity for us what we've heard anecdotally is that people who have treated their attack with decreto band and treated their attack with several talks that is that there's a market difference between these our uh opportunity is to be able to just decrease the the the burden that's associated with just trying to try treat your attack see if you like it better whether

that's a quick start program sampling um keeping people on our open label extension until we have approval whether that's post-trial access we have an expanded access program that we're running for people who don't have access to either a cataban or several charlestad or any he therapy um and really just making sure that we can get in front of people and make that make that uh try it as as simple as possible got it okay i guess moving to the extra opportunity so we had seen with the chapter one trial there was impressive efficacy though in this case you were utilizing two IR BID doses but then the team had done some work to create an XR formulation in order to have a QD version which is currently being tested in the chapter 3 trial so wondering how you you know how how this change in the difference from the the BID IR formulation to the XR formulation how de-risk that is and if you think that the xr formulation the pk advantages that we see there would be able to recapitulate the prior data that we saw great question so as you said in our chapter one data we saw 85 um reduction in attacks that puts us squarely within the the competition for individuals right now so we're really really happy with that phase two data

Our goal for phase three is to be able to confirm those findings. So we're hoping to see 80% to 85% attack reduction in our phase three. As you mentioned in the phase two, we were using BID dosing of a PK that is rapidly absorbed. So there's a very quick peak. And then it comes to a trough at about hour 12. So around hour 12 and hour 24, there is an opportunity for vulnerability for a breakthrough attack. This is when the therapeutic threshold drops below or the plasma exposure drops below the therapeutic threshold, which could open somebody up to a breakthrough attack. Now, because the tablet form is acid stable, so it passes through the stomach into the gut, once the pH starts to raise in your gut, the tablet will release ducrotepam. that slow absorption through the gut and in the colon enables a much stabler pk curve that we have seen from from uh phase one modeling enables you to have coverage for over 24 hours um which is ideal for for once daily dosing now we've only seen this in phase one of course our phase three data will show what it shows, but we have seen in an investigator-initiated trial in acquired angioedema in four patients, so still very small, that those four patients save one attack on day two of one patient, were attack-free for almost two years. So we're hoping that this XR formulation protects from any phase two to phase three efficacy degradation that some people see when they expand out their clinical trial.

Yeah, so I guess, is there any color that you might be able to provide on what the fidelity of the ongoing phase three is, at least even in terms of study conduct, in terms of, you know, all other things different, you know, the formulation is different, but how has the study conduct been versus what we saw before, and is there anything you might be able to speak to on the baseline characteristics of the patients that are involved?

So we have not seen baseline characteristics in terms of attack rates yet. We stay very clean and blinded to that data. We want to be as pristine as possible when we're looking at that data. So having seen that information, of course, we have a DSMB that monitors the data for any safety concerns. As we've moved from phase two to phase three, we have included adolescent patients in our We have a more global footprint, so in addition to North America and Europe, we're also enrolling in Latin America and Asia Pacific. Now, we included about 90% of the same sites in RAPID 3, which was our Phase 3 on-demand study, as we did in the Chapter 3, the Phase 3 prophylactic study. With that, we have confidence in just the quality of data that these sites are giving We saw from repeat one to repeat three that actually there was an improvement in efficacy and that the data quality was really clean. So although we're going to new sites compared to other HEE studies, they're not new to us and not new to far virus. So we're really pleased with the quality of data that we've seen there. Like I said before, we're also including normal C1 patients in that study. so all of these kind of uh opportunities for for more heterogeneity we have done the same things in the repeat three study and like i said saw an improved efficacy so that gives us some confidence in our ability to to run a good study got it then you know we tend to be bullish on our end too based on the analysis that we've done that chapter three has a very good chance of working out and showing good efficacy.

But, you know, assuming everything goes well and this is approved, how do you see the commercial dynamics playing out, especially the switching of patients from those who are otherwise maybe well-controlled on oral prophylactics already? Some of the survey work that we've done as well seems to indicate that, you know, some doctors might actually think about switching a portion of their patients off. But how do you see patient behavior changing with the potential oral that might have injectable-like efficacy with a very tolerable safety profile?

Great. There are four main segments that we're thinking about when we approach the prophylactic space. So number one is new patients' prophylaxis. Assuming all things are the same, right, same efficacy, same tolerability, we know that 80% of physicians would start a patient on and oral therapy the least invasive route of administration and you still have the same efficacy so each year in the united states there are about 200 to 250 new patients that start on prophy we get 80 of that let's say 100 of them then we're able to uh to really stack those year over year right we're not gonna keep 100 of patients on every year but maybe the the switch rate is 7%, 10%, right? So we're able to really stack that year over year. That's the first segment. Second segment is people who have tried the other prophylactic oral and come off of it for whatever reason, whether it's efficacy or tolerability. We know that that's about 1,900 people right now. Those people are people who have already indicated that they are open to switch and that they want an oral therapy, but they don't want to forego efficacy and tolerability. I don't want to say they're easy to switch, but there's certainly low-hanging fruit there that we would definitely target very early on in our launch.

The third set of people are people who are on Orlodeo right now, right?

These are people who may be seeing improved efficacy, right? They may have gone from eight attacks a month to two attacks a month. However, two attacks a month is just the baseline for where we start to provide efficacy. So although they may say, oh, this is so much better than what it used to be, there's still an opportunity for improvement there. If we were able to go to them, to those people and say, you still get to keep your daily oral, but instead of two attacks a month, why don't you have maybe one breakthrough attack a year?

That could be an interesting conversation with those patients.

And then lastly, there are the people who are still on injectables right now because they don't want to forego the efficacy. They may say, I'll stick with my Texiro because I really am well protected. I would love to try an oral if the efficacy were equivalent to what I get with my Endembry, Texiro.

Got it. And then we've seen some development of longer acting injectables as well. How are you thinking about what the dynamics of the market may look like with those potentially approved as well?

Great question. So as we've done our market research, we have asked people, when do you prefer a daily oral versus a long-acting injectable? And so we took daily oral versus once every two weeks, every month, two months, three months, six months. And it's only when you get to a daily oral versus once every six months that you start to see about a 50-50 split in that market, right? Half the people prefer a daily oral, half the people prefer a long-acting injectable at six months. Let's assume that Nevenobart, which is right now the only drug that can potentially get to six months, also has the same efficacy that we're seeing for Ducrectivant, but also other injectables. So they're in this 80% to 85% attack reduction. 50% of the market goes to orals. 50% of the market goes to injectables. Now, we also know that none of these therapies are going away completely, right? People are still on Synrise and Higarda. So let's assume that 5% of each drug is retained, right? 50% of the market on oral. 5% goes with Orlodeo. Ducryctoban, as we were hoping to put up really strong efficacy, gets 45% of that market. Within the injectables, you've got Synrise. You've got Higarda. You've got Texira. You've got Andenbury. You've got Donald Delorsen. And you've got all of these other therapies. If each of those get 5%, then even the winner in the injectables is only getting a portion of that. So it's a crowded market in the injectable space.

And then I guess if you could talk a little bit more about your unique role as a company, because I think Farverse is the only one that will potentially have an on-demand therapy and also a prophylaxis available as well. So how are you thinking about what the commercial synergies, what commercial synergies you might be able to derive and how you could potentially leverage that to gain more of a dominant market share within this market?

Yeah, absolutely. So one really important strategic piece for us is the data that supports the use of Decryctiband XR plus Decryctiband IR. So we have some mechanism on mechanism data right now that says you can use a B2 receptor antagonist on top of a B2 receptor antagonist. We also have safety modeling supporting that use together. And then we hope to have in the future some Ducryctivant plus Ducryctivant data. Of course, we can't do that until one of them is approved. With that, we can have some very interesting conversations with prescribers and with payers around the portfolio of Ducryctivant, right? If you're able to have the broader label of bradykinin-mediated angioedema, plus the ability to be able to use one brand for prophy and one brand for on-demand, you could become sort of the broadest first-line therapy for all HE and pretty kind of mediated angioedema. Makes sense.

Maggie, I think we're just about out of time, but I very much thank you for this opportunity to talk about the progress and looking forward to the data in a couple of months.

Yeah, absolutely. Thanks, Kevin.