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

Good day, everyone, and thank you for standing by. Welcome to the Chapter-3 Topline Data webcast. [Operator Instructions]. I would now like to turn the conference over to your speaker host Maggie, please go ahead.

Thank you, and welcome to the top line data announcement of Chapter-3, a Phase III clinical study of Deucrictibant extended-release tablet for the prophylactic treatment of hereditary angioedema tax. My name is Maggie Beller, Head of Corporate and Investor Communications at Pharvaris. Please note that today's webcast is being recorded. and the slides will be uploaded onto the Investors section of our corporate website immediately following the call. Please note that statements of our guests today are their own and not those of Pharvaris, and Pharvaris makes no representation as to the adequacy, fairness, accuracy or completeness of the information in their comments. In addition, our presentation today will include forward-looking statements, including, but not limited to, statements regarding Deucrictibant and its potential as well as our preclinical and clinical studies regulatory interactions and future plans. Such forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially from those projected. For additional insight regarding the various factors that could cause such differences, please see the section entitled Risk Factors in our annual report on Form 20-F and our other filings available on the SEC's website. In addition, any forward-looking statements represent the company's expectations only as of today. While we may elect to update these forward-looking statements, we specifically disclaim any obligation to do so unless required by law. We are joined today by Dr. Marc Riedl, Professor of Medicine at the University of California, San Diego, Principal Investigator in the Chapter-3 study and a globally recognized expert treating physicians, who will share his perspective on the Chapter-3 data and on their relevance for clinical practice. Thank you, Dr. Riedl for joining us. During our call, Pharvaris Chief Executive Officer, Berndt Modig will speak to Pharvaris' continued commitment to provide medicines that can further advance the management of bradykinin-mediated angioedema. Pharvaris' President, Dr. Peng Lu, will go through the top line efficacy and safety findings from the Chapter-3 study. Additionally, Pharvaris' Chief Commercial Officer, [ Lynne Subrin ] is available for the Q&A portion of the call. I'd now like to hand the call over to Berndt Modig. Berndt?

Thank you, Maggie, and good morning, good afternoon, everybody. Pharvaris prides itself on being a trusted partner to all stakeholders in the FA community. I'm proud to once again speak to you as we execute another key milestone for our company. Starting with the on-demand program. Positive Phase II data were followed by positive Phase III results in December 2025. Most recently, the FDA accepted our NDA submission, bringing us one step closer to making the correct even available for on-demand treatment of HAE attacks. The next catalyst for the on-demand program is the potential approval in April '27 of the [indiscernible], which may represent a new standard of care for on-demand HAE attack treatment. Now turning to long-term prophylaxis. We have similarly built a strong foundation. Positive Phase II data were announced in December 2023. Today, we build on those with positive Phase III results, which support Deucrictibant XR as a potential long-term prophylactic therapy. Looking forward, we continue to generate additional evidence for the Curitiba in acquired angioedema through the CREATE Phase III study, which results from the prophylactic part of the study anticipated in the first quarter of 2027. We expect to submit our U.S. NDA in prophylaxis during the first half of 2027. So now when you step back and take a look at the entire time line, what's exciting is that we have already crossed several major value inflection points and the upcoming milestones have the potential to transform Pharvaris into a commercial leader in bradykinin-mediated angiodema. I'd now like to hand over the call to Pharvaris President, Dr. Peng Lu, to present the Chapter 3 data. Peng?

Thanks, Berndt. Before reading the data, I would like to take this opportunity to sincerely thank the HAE community, especially study participants, their families, investigators and science stuff, our study partners and all over for their invitable contribution to clinical research, especially the Chapter 3 study. Chapter 3 was a randomized double-blind placebo-controlled Phase III study of all administered equipment, extended-release tablets milligram once daily for the prophylaxis of hereditary and edema attacks. Eligible participants were aged 12 and older with HAE, Type 1, Type 2 or HAE, with normal C1 inhibitor. Participants were randomized in the Q1 ratio which was stratified by age and baseline attack rates. In total, 85 participants were enrolled with 55 into the [indiscernible] and the certain with placebo. Baseline demographics and HAE DB's characteristics were generally balanced between 2 groups and consistent with the overall HE population. The main age was about 39 years old and the 4 adolescent were enrolled in each group. Most of the participants had HAE type 1 or 2. A total of 5 participants with HAE normal C1 inhibitor were enrolled. The baseline attend rate was comparable between 2 groups. with a min reach approximately 3 to 4 attacks per month. After years of dedicated effort, we are proud to announce the Chapter 3 study successfully met its primary endpoint, demonstrating a highly statistical significance and clinical mile reduction in HAE attack rate. Participants treated with Deucrictibant XR experienced substantially fewer HAE attacks during the entire 24 treatment period with an estimate attack rate of 0.35 attacks per month with Deucrictibant versus 2.06 attacks per month with placebo. These reccurence but 83% reduction in a tetra versus placebo, which was highly statistically significant. Of note, Chapter 3 is the first and the only pivotal Phase III study to enroll patients across the full spectrum of HAE, including participants with HAE with normal C1 inhibitor. In contrast, all other pivotal studies have exclusively enrolled patients with HAE type 12. Among the 8 participants with HTE Type 1 in Chapter 3. Deucrictibant XR achieved 87% reduction in monthly attack rate was placebo. Taking together, these funding demonstrates Durban provides injectable like efficacy with the convenience of owner therapy. This slide highlights one of the most important attributes of Deucrictibant XR as a prophylactic therapy. Its early onset of protection combined with durable effect over time. Consistent with its pharmacokinetic profile, Deucrictibant XR reaches therapeutic exposure within the first day of dosing has achieved steady state within 2 to 3 days. Correspondently, Chapter 3 shows that the protection of equitable with maximize within the first week of the treatment and the maintain throughout the study duration. Moving on to some of the key secretary endpoints. Deucrictibant XR demonstrate robust and highly consistent treatment benefit in reducing moderate to severe attacks and attacks treated with on-demand medication. In the responder analysis, all base I participants receiving equities achieved at least a 50% tax reduction from the Phase 1. With the most stringent thresholds, almost all and 2/3 of participants achieved at least 70% and 90% reduction, respectively. Nearly half of the participants treated with equity remained attack-free throughout the entire 24-week treatment period. These results demonstrate meaningful attack control and reinforce the robust efficacy of Deucrictibant XR across multiple clinical relevant measures. Beyond the reducing attacks, we also observed meaningful improvements in how participants fold and functions in their daily life. As shown in this slide, participants receiving durian experienced substantial improvements across all domains of angiodema's quality of light cuisine, including functioning, fatigue on far machine and also nutrition. Across every domain, reductions in AECO scores from baseline to week 24, we're consistently greater with Durian compared to placebo. These results demonstrate the benefits of Deucrictibant XR extends beyond attack prevention alone, translating into broad impact of the treatment from the meaningful improvements on patients' day-to-day quality of life, from the increment with well tolerated with the most events being motor moderate in severity. The most common adverse events across both groups will offer respiratory tract infection, nasal fungitis and headache. The one treatment-emergent serious adverse events also reported in this table as a Grade 4 event with [indiscernible] in a patient with a prior history of repeated laryngeal incubation, which was considered not related to study drug by the investigator. The 3 participants with Grade 3 adverse events included to inflection as the 2 people with Level 2 liver enzyme innovation. One of them discontinued study drugs, the other remain on treatment and complete the study. The discontinuation in the placebo arm was due to urticaria. There was no evidence of increased risk of gastrointestinal side effects. [indiscernible] treated emergent adverse events were evenly balanced between equation and the placebo group, all of the amounts are moderate. As we have shown today, Deucrictibant XR demonstrated meaningful and sustained attack prevention starting from week 1 Chapter 3 study met its efficacy and the patient report outcome endpoints with 83% reduction plus placebo in the overall HD population and 87% reduction for the Type 12 HDE participants. Deucrictibant XR was very well tolerated. Now I would like to introduce Dr. Marc Riedl, a world-leading HD expert to speak about the existing treatment landscape in the long-term prophylaxis of HAE. The [indiscernible] in prevention of HAE attacks take opinion on the clinical profile of Deucrictibant XR and the potential of the equities as an oral medicine. Marc, please.

Thanks very much, Peng, and good morning to everyone. I appreciate the invitation to join the call and give me the opportunity to just make a few brief comments, I think, is the data you've seen may relate to clinical practice. So for a very brief background, I've been working in the HAE space as a specialist for about 25 years now, managing a large group of patients over that time and also conducting research and clinical and translational research and the condition. And so I would just mention as people on the call likely know, we've really seen tremendous progress over those years with advances and therapeutics for HAE and understanding the condition. And that's occurred both for on-demand treatment or trading attacks, but very importantly, for the prevention of attacks. And I would say in clinical practice, there's been an increasing emphasis on preventing HAE attacks. Because we do think that's the way to reach the goal of really normalizing people's lives and looking carefully at quality of life, as you just saw was incorporated into this trial. So as people know, patients do have increased treatment options. We have achieved a lot over the years. But we've not entirely reached that goal of sort of normalizing life for all patients. And I think that's why we continue to see the work that we're seeing, the clinical trials. That's why patients continue to enroll in these studies, and they continue to be completed because we do have unmet needs yet. We do have room for improvement in terms of managing this condition, which, as you know, is a lifelong at this point, lifelong chronic condition. So just a few comments on what we still need in HAE and how the data you've seen on Deucrictibant might help us achieve or meet those needs. I would first say that the burden of treatment is a real thing for patients having to take their medicine, the roots, the dosing, the schedule, this is a real issue, and it's something we spend a lot of time talking to patients about the burden of treatment does affect quality of life. And so in my experience, many patients are very interested in the oral route, the oral medications as a more tenable, a more acceptable and tolerable way to take their chronic treatments due to portability and all the things that we know can be advantages of oral treatment. The oral medications for prophylaxis in HAE have had some limitations to this point. That includes reduced efficacy compared to the parenteral medications or limitations due to certain side effects. And so I think the data that you've just seen is really encouraging. We're seeing the benefits of oral treatments now with efficacy that looks quite similar to the subcutaneous administered medications. And I think this will be very appealing to clinicians and to our patients as an oral medicine that can really achieve a strong efficacy in preventing attacks and it appears to be very tolerable in terms of side effect profile. The second thing I would say is that we really do work to individualize care to optimize outcomes. And by that, I mean we do see variable efficacy and tolerability for any and all of the medications that are out there. So having treatment options are very important. I think this will be -- if it comes to the clinic, will be a very important treatment option. And I'd point out that this is a unique mechanism of action for preventative treatment, the B2 receptor antagonism. That unique mechanism of action makes as a novel treatment option where we might, in fact, see this improving outcomes for patients who to date have not seen the efficacy or the tolerability that we really aim for. And the last thing I would comment on is this group of HAE with normal C1 inhibitor. As you heard, this is a study that enrolled a small group of those patients, and this is a condition that's been very challenging to treat in part because we understand it has a bit of a variable pathophysiology, but we strongly believe that most, if not all of these patients have a bradykinin-mediated angioedema. So, this is, again, a mechanism blocking that [indiscernible] receptor that may give us real advantages in preventing attacks for this group of patients, the HAE normal C1 inhibitor patients and really allow us to better manage these patients regardless of the reason the pathway that there is brain in this regulation. So I think in totality, the study data that you've seen today really are encouraging that if approved for use in clinical practice, the price band will be a very important and a very useful addition to the tools and options that we have to manage HAE. And so with that, I'll turn it back over to the Pharvaris team for the next part of the program. Thank you.

Yes. Thank you, Dr. Riedl and Peng, for your insights on the Chapter 3 data presented today. I would like to reiterate my appreciation of the people around the world who have collaborated to generate these data. And let me take a step back to share our long-term vision. Our inspired path to predicate mediated and edema leadership has 3 steps: First, win on-demand treatment by combining effective attack control, a well-tolerated profile oral convenience and reduce the treatment burden; and second, expanding to long-term prophylaxis with the ambition of offering injectable like efficacy and a well-tolerated profile with the convenient oral administration, and as we just heard; third, leverage the B2 receptor platform beyond HAE, expanding into other bradykinin-mediated diseases and building a differentiated franchise. The opportunity is different much bigger than a single product or indication building on one foundational mechanism, we aspire to redefine disease management across the spectrum of medicine mediated anti-de and beyond. The upcoming year should be incredibly impactful favors our PDUFA for decrement in the on-demand setting is in April. We plan to submit our NDA for Deucrictibant in the prophylactic setting in the first half of next year and we plan to announce top line data from the CREATE Part 1 Phase III study in the first quarter of next year. In closing, Pharvaris is steadfast in our mission to improve the standard of care for people living with Bradykinin-mediated Angiodema.

[Operator Instructions]. Our first question coming from the line of Maxwell Skor with Morgan Stanley.

Congratulations to team on the update. So now with two relatively near-term launches, can you talk about just the commercial builds for both on-demand and prophylactic? How do cryptobands in both formulations are uniquely positioned does the dual profile actually change payer conversations or simplify them? And then if I can, just one more follow-up. On read-through, how should we think about the relevant comparator from Chapter 3, either type 1, 2 patients? Or what have we learned from the normal C1 inhibitor patients?

Thanks, [indiscernible], for that great set of questions. And we also will start off by saying that Pharvaris has the vision of commercializing Deucrictibant. We have already early on invested in getting ready for a potential launch and also handing over to Wim Souverijns, Chief Commercial Officer, who actually joined over 5 years ago, and we are well underway in building a very strong team with great experience in this therapeutic space. So over to you, Wim.

Thank you, Berndt. And thanks, Max, for the question. I hope I can answer all of you be are quite a few in that question. I think, first of all, let me say that we are super excited on the commercial side with these data. As you remember, when Chapter 1 came out, we were blown away by this very high level of attack production as we call it, injectable-like efficacy. And that's not confirming the Phase III. So I think together with P3, we are in a fantastic position with a drug that in both treatment paradigms, on-demand and prophylaxis, so really exceptional data. In terms of our commercial preparation, we are well underway. We know that the target audience in the U.S. is around 2,000 physicians, core physicians. And what we've done is we're building a commercial infrastructure that really is going to match that market. By the end of the year, we anticipate to have about 95% of our people in place. Our aim is to vehicle for an organization that portraying the value of the company, the collaboration people with deep experience in HAE and/or rare disease. And based on the interest we get for job opening at the moment, we see the excitement within the community of employees as well for the active challenge that we have ahead. So we are very well poised to succeed that. In terms of the peer question, as the benefit having [indiscernible] that absolutely comes true. And it's actually not the benefit just for the payer. It's actually fundamentally doctors and also patient and categories will tell you having on active drug, 1 molecule in 2 formulations that really cover all your needs in HAE is a super advantage. And we're going to be leveraging that. We're going to be working on that to make that a real benefit also in the market. But from a payer perspective, specifically, yes, that is something that can become an advantage over time. We will obviously launch first with on demand. But once we have the prophylactic option approved that would be adding to that [indiscernible]. Did I cover all your questions, Max?

Yes, I believe so. And then just finally, just on the CREATE read-through as we're thinking about that trial coming up, anything we've learned from Chapter 3? Thank you very much for the commercial side.

Yes, great question, Max. As I mentioned, our CREATE study, the pivotal Phase III study for acquired angioedema due to C1 efficiency is well on track. I think definitely that the Chapter III data is very encouraging and give us a bit more confidence to see a prophylactic treatment effect for part 1 of the CREATE study. Meanwhile, Dr. Riedl, maybe I hand you over to you and also making introduce more about acquired angioedema patients.

Sure. Yes. I mean, I think, for the most part, acquired C1 inhibitor deficiency behaves clinically very much like type 1 and type 2 HAE I mean it is one inhibitor deficiency, of course, the underlying cause is quite different. Due to consumption rather than a genetic deficiency and acquired C1 inhibitor deficiency, but clinically speaking, when we manage those patients the acquired C1 inhibitor patient patients. We use really all the same principles and in fact, the same medications, they're off-label in at least in those regions of the world. But point being that we would expect that success in type 1 and type 2 HAE would predict similar results and acquired C1 inhibitor deficiency. So of course, you have to do the study to prove that. But that would be the anticipated outcome.

Next question in queue coming from the line of Joe Schwartz with Leerink Partners.

Congrats on the results. I have one for the company and one for Dr. Riedl I think the release notes an increase in the percentage of attack-free participants, but it doesn't quantify it. So I was wondering if you could give us any insight into the proportion of patients on Deucrictibant who were attack-free over the 24 weeks and how that compared to placebo? And then thank you for your perspective, Dr. Riedl in your clinic when patients evaluate a prophylactic therapy, what do they anchor on? Is it the percent attack reduction, those that are attack-free or is it the route and frequency of administration. And when there's a once-daily pill, how do you think it will set up in the considerations that patients consider when there's monthly or every other month injections in that trade-off.

Yes. Thanks so much for the great question. But within the Chapter 3 study altogether that we enrolled 5 patients with normal C1 inhibitor Among these supply patients, actually 3 patients received the active treatment Deucrictibant XR. As Dr. Riedl highlighted that for the normal C1 patients due to the different -- the genetic mutation or underlying that different [indiscernible] pathways. The response relatively higher at higher variability compared to the Type 12A patients. Therefore, we [indiscernible] 3 patients, we observed that 1 patient with less than 50% reduction where patients get 90% reduction and 1 patient attack-free. Hopefully, we address your question.

Yes, that's super helpful. And Dr. Riedl, how do you think that a once-daily pill will set up relative to some of the less frequently administered injections that are available.

Yes. Thanks for the question. I really like your question because the complexity of what goes on in the clinic. And it's -- it's a little bit hard to answer, meaning your question, what do patients anchor on? What are they most interested in? I think it's a combination of things. And I sort of always joke. I'm notoriously bad at predicting what specific treatment an individual would chose because these conversations are complex with a lot of factors. But I will tell you that just my experience. I think efficacy almost always carries the day, meaning that it's got to work. And I think -- we spend a lot of time talking about efficacy. We do discuss from the pivotal trials, the average reduction and a 10% reduction in attack rate as kind of an important endpoint. I will say that patients are also increasingly interested in this attack-free outcome that I think you mentioned what are the chances from the study that I won't have a tax at all for long stretches of time. But I think closely behind efficacy, and you touched on it, is the route or the -- I call it the schedule, right? What do I have to do to get the benefits of the medicine. And my experience is that patients are very, very interested in oral medications. Generally, patients don't like injections or infusions. Of course, as you said, as these become less frequent, it might become more palatable. But we've seen tremendous interest in the oral agents that have been available to date, whether those are appropriate on demand. And I see that continuing. So I do think that there is sort of an advantage to the oral route for most patients, perhaps not all, and that, that's something that they can picture themselves adhering to over time, a daily pill, it's portable, it's easier to take with them when they travel and it becomes part of their routine. So I do think that, that is attractive to patients. is this drug going to be for everyone? No. That's why it's nice to have options, but I do think we're going to have a lot of conversations if and when this is in the clinic, a lot of conversations, people will be asking about this because of the considerable interest in the oral routes overall.

Our next question in queue coming from the line of Steve Seedhouse with Cantor Fitzgerald.

Congratulations on the results. First question I had -- I was just hoping you could expand on the safety profile you saw in the study. I saw there was -- I think there was a few grade 3 events, one Grade 4 event that I think you said was a little range deal HAE attack, which seems fine. And then there was one HAE as well. So would you mind just expanding on those HAEs and the overall safety profile observed in the study.

Yes. Thanks, Steve. I appreciate the question. The as illustrated in the presentation, we do observe the one that serious adverse events, it's a [indiscernible]. Actually, for this, this is actually a normal C1 patient. As before joins the CAFTA III study, this patient report in 19 or Lorena attack during the screening period. That's why due to the long time [indiscernible] and also multiple times incubation, these patients actually have local [indiscernible]. That's why during the study, actually, this patient achieved a 90% type reduction and 1x the patient due to the local quarter-to-quarter and hospitalized. And during the assessment, there is no swelling during the laryngeal microscope and the patient consider it's not the PI considered is not treating related. Actually, during foot, the PI told the patient very happy once we joined the study even back to work. We really feel proud that we do credit help our patients here.

Okay. Super helpful. I was hoping also you could comment on prior prophylactic use by patients entering the study like what proportion had been on prior prophylaxis versus treatment naive? And did you have representation from prior [indiscernible] use specifically?

Yes. Excellent question. I believe during our demographic flyback we show around maybe between 20 to 30 patients. on prophylaxis price towards the study. Yes, that actually these patients have that organs have the run us and also C1 inhibitor [indiscernible].

Okay. And then Berndt, you mentioned in the press release and in your closing comments that this encourages the company to develop novel therapies or maybe even Deucrictibant for [indiscernible] diseases beyond angioedema. And of course, you recently published this review sort of summarizing a bunch of indications where B2R may be involved. So I was hoping you could expand on your plans going forward in that regard.

Yes, sure. So we are -- as you also pointed out, evaluating, looking at rate kind of mediated diseases that could potentially be product extensions of Deucrictibant. So that is in the sort of final stages of evaluation, and we plan to make some decisions on potential starting from clinical development and to generate data for these other indications. We have not publicly disclosed or define exactly what that is yet. But in due course, we will provide more information about that. And so stay tuned.

Okay. Great. And just last one quickly. Can you say what proportion of the 85 patients enrolled and are continuing in the Chapter 4 open-label extension and I guess, what's the plan for data disclosure from that going forward?

Yes. Excellent question. As I mentioned, the 83 patients continue the study out of 880 patients roll over to the CHEP study Currently, the study is ongoing, and we have continued to monitor long time efficacy safety with the [indiscernible] study.

Our next question coming from the line of Jon Wolleben with Citizens Bank.

Two for me. I'm just wondering if you could give us some sense of the most common HAEs on Deucrictibant, whether it's more than 5% or 10% of incidence rates. And then for Dr. Riedl, if Deucrictibant becomes available in both the on-demand and prophylactic setting, can you walk us through how you think about shared decision-making and introducing this option to patients when they come in or patients thinking about switching to a new therapy?

Yes. As presented that for the safety section, the most common adverse events per reparatory set infection may so very guide us and also headache as I showed here, the overall is been like placebo and active group. Marc? I believe second question for Dr. Riedl. Do you have any follow-up safety questions?

No, that was helpful.