Good morning, and welcome to the Pharvaris Virtual Investor Day. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentation. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. As a reminder, this call is being recorded, and a replay will be made available on the Pharvaris website following the conclusion of the event. I'd now like to turn the call over to Maggie Beller, Head of Corporate and Investor Communications at Pharvaris. Please go ahead, Maggie.
Thank you, Tara. Good morning, and thank you for joining us. Today's virtual event will focus on the unmet medical need of people living with hereditary angioedema and Pharvaris' late-stage lead drug candidate, deucrictibant, which is being developed for prophylactic and on-demand treatment of HAE attacks. 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 information regarding various factors that could cause such differences, please see our section entitled Risk Factors in our annual report on Form 20-F and our other filings on the SEC's website. In addition, any forward-looking statements represent the company's expectation only as of today.
While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so unless required by law. We are pleased to have two well-known and widely recognized experts in the field of HAE join us today for this event, Dr. Michael Manning, President of Allergy, Asthma, and Immunology of Scottsdale, Arizona, and Dr. Raffi Tachdjian, Assistant Clinical Professor of Medicine and Pediatrics at the David Geffen School of Medicine at UCLA. Dr. Manning will first speak to certain unmet medical needs and the current treatment landscape for the prophylactic management of HAE. Dr. Tachdjian will then discuss some current unmet medical needs in the HAE treatment of attacks in a pre-recorded presentation.
We are also joined today by members of our management team and our Chief Executive Officer, Berndt Modig, who will out-outline Pharvaris' product strategy, strategy for deucrictibant. Then, our Chief Medical Officer, Dr. Peng Lu, will present data supporting the differentiated therapeutic profile of deucrictibant for both the long-term prevention and on-demand treatment of HAE. Following Dr. Lu's remarks, our Chief Commercial Officer, Dr. Wim Souverijns, will speak to current HAE market dynamics, including results of a company-sponsored survey exploring treatment decisions by both physicians and those living with HAE. At this time, we'd like to welcome Dr. Michael Manning to discuss our prophylactic treatment landscape. Dr. Manning?
Hi, and you know, I wanna thank Pharvaris for inviting me here today to speak about the landscape of long-term prophylaxis. A little bit about me. I trained at Scripps Clinic in La Jolla, California, under the supervision of what I consider one of the premier experts in HAE. And so I've been dealing with HAE for a long time, and I think the way we look at HAE as researchers and clinicians in the U.S. is different than the rest of the world looks at it. As we started our research, we started looking at prophylaxis. Treatment was the first thing that was approved in 2008, and so we tended to adopt a prophylactic approach to the management of HAE sooner than the rest of the world, which was using on-demand therapy.
The landscape has changed since two thousand and eight. We started out with an IV C1 esterase inhibitor product that gave us about 50% reduction in attack rates, and with the initial studies that got that approved, and we were really excited about that. We learned over time that that dose was probably not appropriate, and we started increasing or changing the dose. Then, the landscape changed a little bit with other targets as we understood the pathway and areas that we could target with hereditary angioedema to make an impact on controlling these or preventing these attacks from happening. So we looked at kallikrein and bradykinin receptors, where we can look at all these targets.
And so as we've improved, we've been very excited, and as a clinician and as a researcher, I think our goal is to look at trying to normalize somebody's life to where they don't think about hereditary angioedema anymore. They're on a treatment option that hopefully makes them attack-free. That's our ultimate goal. I know that's reaching for the stars, but I think we always wanna reach for that. I think we're getting closer and closer to that with the options that we've had. Even though from 2008 to 2024, our treatment options have improved a lot. We've got both an oral option, along with our injectable options right now.
We've kind of gone away from the IV option, which is wonderful because patients they're, you know, initially, that's all we had, and their veins got really tired over time. So they're always looking for a different route of administration. And I think when we look at the unmet needs that we're seeing with long-term prophylaxis now, even though we're doing well, there's always room for improvement. There's no product that's perfect, and so the agents that we have don't necessarily work for every HAE patient that we have. Patients are becoming what we call needle-fatigued. Initially, it was IV needle and administration. Now we've got injectable or subcutaneous administration, and finally, an oral option came out and that was met with enthusiasm by the patients.
I think they're looking for different and easier ways to administer their medication that takes some of the treatment burden off of them. When we talk about the burden of disease with hereditary angioedema, it's not only the burden of an attack, it takes you out of work, out of school. You may have an attack for two to five days, but it's also the burden of administering the medications that you're using. There's a burden to that. The other burden is the worry of hereditary angioedema. When am I gonna have my next attack?
Part of our treatment is to really try to get these patients to hopefully relax and not have to worry so much, because one of the bigger triggers that we see, stress, anxiety, helps kind of get this perpetual motion machine going, where the more they worry about the attack, they have another attack, they worry about their next attack, and it just kind of snowballs over time, and we want to interrupt that cycle. Patients are still looking for kind of a better mousetrap, for better... for a lack of better terminology, ease of administration, something that I think is portable, that they don't have to pack a lot of equipment, whether it's IV supplies or injectable medications that may need to be kept cool or refrigerated.
And those that travel a lot, I think oral options are still a wave of the future that they're looking for, both, and Dr. Tachdjian will talk about this, on-demand therapy plus the prophylactic market. And then just improved efficacy. We've gone from 50% improvement in attack rate up into the seventies and eighties as we've gone on. Like I say, we wanna get to 100%, if at all possible, but I think once we get up to looking at 90% or greater, I think that's a great target to look for. And as we've researched these products that are coming out, I think we're getting closer and closer to that. And so that is where I see the direction that we're looking at for a prophylactic market.
As a clinician, the more options I have, the better. I can always then find something that will work for an individual. You would think that with patients, a genetic condition that's running in families, that everybody would gravitate to the same product, but that's not always the case. As an example, I had a father in my office. He finally got his teenage son in to me eventually, and his father was on a subcutaneous injectable prophylactic medicine, was, I think, attack-free for about two years at that point. The son, seeing how his father was doing, wanted nothing to do with the needle. He said, "There's a new oral agent that's out on the market. I know my dad's doing great. I'm not my dad.
I wanna look for an oral option," and I think for some of the unmet needs, especially in the teenage population, the young adult population that may be going to college, this is really a disease of kind of childhood and young adulthood. They're looking for something that allows them to administer their medicines, treat their disease, and somewhat fly under the radar. If you think about this, they're not getting a needle out. They're not getting an IV set out. It's something that they can take with a little bit more discretion, and the rest of the world around them, their college roommates, don't necessarily have to know what's going on.
The other avenue, when we look at one of my philosophies with patients and treatment with injectable or IV medications, and then you can come along and maybe come up with an oral option that works, I think there's a little bit of a mental aspect, as patients feel they may not be quite as sick if they're using an oral agent versus something that is being injected. Because it's, like you say, it's, you know, discreet. A pill's not as intense as an IV or an injection, and I think that mindset that they can get into actually helps their overall disease burden improve. So, I'm always looking for newer medications, improved routes of administration, improved efficacy, and along with that efficacy is also an improved side effect profile.
As we've gotten along in the injection market, you know, injections don't always come pain-free, and the medicine itself can be irritating or painful to inject. We're getting better at that also. But still, most of my patients are- if we can find the best oral agent out there, I think that's gonna be a market that they're gonna gravitate to. And I think help us as clinicians, manage them, keep them under better control, keep them out of the emergency room, and have this disease not impact their life like it was impacting five, 10, 15, 20 years ago.
Thank you, Dr. Manning, for your insight. Dr. Manning will be available for Q&A at the end of this session. Although he could not join us today for a live presentation, we're pleased that Dr. Tachdjian was able to provide us with a prerecorded presentation, during which he outlines his view on the current unmet medical needs in the on-demand treatment landscape. We will now listen to Dr. Tachdjian's remarks.
Hi there. I'm Raffi Tachdjian. I'm associate professor of Allergy and Immunology at David Geffen School of Medicine at UCLA, and I'd like to talk to you a little bit about on-demand therapy and how that landscape looks like in hereditary angioedema.
... I'm sure by now you've heard a lot about how rare the condition is and the burden of the disease, but we also often think about the burden of treatment. And one of the kind of big legs of treatment is on-demand therapy. And according to the guidelines, both in the United States and worldwide, every patient is recommended to have at least two doses of an on-demand therapeutic on hand, whether they're on a prophylactic therapy or not. And this is kind of the same paradigm that we see in other disease states, for instance, food allergy. You may not choose to eat that peanut, but there may be an emergency, and so you need a rescue medication.
Two doses should get you out of trouble or at least into the hands of an emergency department or someone who's gonna be able to take over. Now, that said, having those on-demand therapeutics on hand doesn't just complete the game, because unlike allergic angioedema, where I might limit the chance or completely knock out the chance of having a reaction or swelling from an allergic cause on a particular day, say, if I had peanut allergy or a bee sting allergy, I'll just not eat or stay home, indoors, et cetera, or penicillin allergy and not take any medication.
For the hereditary angioedema patient, as soon as they open their eyes, and particularly if they're not on a prophylactic therapy, they're not sure if that day they're going to have an attack, and furthermore, if they're gonna have to treat it. So that kind of anxiety is the black cloud that looms over the head of the HAE patient compared to other angioedema types of diagnostically name-given patients. So the anxiety is huge. And, in fact, we're looking at inter-flare anxieties or inter-attack anxiety measures currently to just see how big of a burden that piece is for this rare disease. That said, we've come a long way in just the span of about five years, from around 2009 to the mid-2010s, where we had a number of sequential acute therapeutics get approved by the FDA.
These started with infusible or IV C1 esterase inhibitor, to another on-demand injectable that had three different injections that had to occur at the same time, subcutaneously. Furthermore, there was another C1 inhibitor, recombinant, that was infusible, along with a single injectable rescue medication. Now, these obviously are can be painful, can cause burning at the site, so injection site reaction, et cetera. Some are plasma-based, so we worry about the warnings for thromboembolic risk, et cetera. All in all, they still work, but what kind of ensued from there is the burden of treatment, where you might have to store this in a particular place, prepare it. If you're a college student or even someone at work, someone might see you, and that causes self-image issues, that you're actually administering something, must be something wrong with you.
And the progression from there has been patients in certain surveys seeking out something that's less burdensome as a treatment therapy. And obviously, much like in the prophylactic world, in the on-demand world, an oral formulation has been one of the kind of demands or wish list of patients. And so we can see that it's not just treating the attacks, but obviously we want good efficacy, but safety as well. And so we wouldn't be prescribing something to our patient if it wasn't safe in the first place.
And so that's what's exciting about this field at this time, is even though we've made giant strides from not having much on hand back in the late 2000s, to now having an assortment and actually pushing towards easier and more amenable treatments, particularly in the on-demand arena or in that kind of landscape, where it's exciting to see products in the pipeline being developed to meet those unmet needs.
And so to kind of round it out, these hereditary angioedema patients who are part of the orphan disease network have really had to endure times where it was called essentially a medieval disease with medieval treatment, to now getting finer and finer, or I should say, with more finesse and more safety and more efficacy that surrounds these treatments, all coming at an even more comfortable kind of delivery mode. As we think of these patients being susceptible to not just multiple morbidities, but actually mortality. And I had the father of a patient that I was treating just last year had an acute angioedema attack while being incarcerated and was thought to be looking for a way out to go to the nurse's office, et cetera, basically asphyxiated to death.
Those are the kind of flames that I carry to be sure that there's no other mishap out there, not just for this condition, but for any human being. But since we're talking about HAE, I reiterate that patients should have that access to the two doses, be well-educated around it, on how to use it, when to use it. We talk about the earliest time that you recognize it, even if it's in the prodrome, and it fits the pattern of your attack, that qualifies as an attack that should be treated.
And then add on to that the fact that we're getting more pleasant or amenable for the patient to be compliant and adherent with these more novel therapeutics. It makes it a beyond exciting time to be an immunologist in this field, and actually having some of my other specialist colleagues be jealous that we've made such great strides in a decade and some change, so I hope that kind of brings some color and content to the on-demand world within hereditary angioedema, and hopefully it helps you differentiate it from other sources of swelling, because this is a unique and particular kind of scenario that we've gotten better and better, and we still have a little room to improve, and that's what makes it exciting, so thank you for your time.
We are appreciative of Dr. Tachdjian for taking the time to provide this expert perspective. With this review on the current HAE landscape, I'd now like to turn the call over to Pharvaris' Chief Executive Officer, Berndt Modig. Berndt?
Berndt, you're on mute.
Yes, thank you, Maggie, and, thank you, Dr. Manning and Dr. Tachdjian, for these, in today's insights and comments and contributions to today's event. As Dr. Manning and Dr. Tachdjian mentioned, there have been incredible advancements in therapies for HAE, and many of us at Pharvaris have had a hand in these developments, and we're proud to have such a deep history in the HAE drug development space, including myself through my time at Jerini, where the team achieved, the EU approval of icatibant, which is now branded as the Firazyr. And a co-founder of Pharvaris, Jochen Knolle, is the inventor of icatibant and also the brain behind the molecule, the deucrictibant, which we'll talk more about later. Of the statements, both, Dr.
Manning and Tachdjian. I note a clear appreciation for previous work in this disease state, and yet there remains unmet needs for people living with HAE. It's clear that people are seeking additional options for HAE to provide injectable-like efficacy, placebo-like tolerability, but with the convenience of an oral pill. Since our founding in twenty fifteen, Pharvaris is committed to pioneering science for patient choice. Our strategy has been to develop two distinct products from one molecule to manage hereditary angioedema by preventing attacks from happening with the once daily oral tablet and by treating attacks as they occur with an oral capsule. I'll now turn over the call to Pharvaris' Chief Medical Officer, Dr. Peng Lu, who will discuss the differentiated product profile for the deucrictibant. Peng?
Thanks, Berndt. As we heard earlier from the presentations by Dr. Manning and Dr. Tachdjian, despite the availability of several HAE therapies, there remains significant unmet needs in HAE, both with respect to the prophylaxis and on-demand treatment of attacks. We believe that the deucrictibant IR, immediate-release formulation, and XR, extended-release formulation, have the potential to address this challenge so that more patients can better manage their angioedema. Deucrictibant is the only HAE therapy in development that allows for oral administration in both prophylaxis and on-demand setting. The XR extended-release formulation for the long-term prophylaxis, while the immediate-release IR address on-demand treatment for either acute or breakthrough attacks. In the Phase 2 development, deucrictibant has demonstrated the potential for injectable-like efficacy for prophylaxis. Meanwhile, deucrictibant can achieve steady state within just two to three days.
This early onset effect is expected to protect the patients against angioedema attacks from the initial treatment with deucrictibant. With the successful development of XR formulation, deucrictibant XR tablets allows for once daily prophylactic dosing, which we believe there will be a positive advancement regarding to the adherence and convenience in conjunction with injectable-like efficacy. We are so excited about the R formulation, also developed for on-demand setting too. In the Phase 2 study, within 15-30 minutes, deucrictibant IR reached the therapeutic exposure and halts the attack progression within just 30 minutes. Meanwhile, due to the long effect exposure with deucrictibant, high proportion of attacks are completely resolved with only single dose of deucrictibant. In March of this year, we initiated our global pivotal Phase 3 study of deucrictibant IR for the on-demand treatment of HAE.
This crossover study aims to enroll about one hundred and twenty participants, including both adults and adolescents. All patients will treat two attacks and evaluate the efficacy and the safety of deucrictibant in a crossover blinded fashion. The enrollment in RAPIDe-3 is progressing as planned. We have not provided specific timeline for data readout yet, but plan to provide further guidance as we continue the study. RAPIDe-3 is designed to collect a robust set of data to demonstrate deucrictibant provides injectable-like efficacy and resolved attack with a rapid onset of the symptom relief and a fast symptom resolution with only single-dose treatment. In addition, with the convenience as oral capsule, deucrictibant IR has the potential to enable patients to treat all attacks early.
The primary endpoint of RAPIDe-3 study is the time to onset of the symptom relief, as measured by PGIC, the Patient Global Impression of Change, a little better, supplemented by key secondary endpoints of time to substantial symptom relief and time to complete symptom resolution, detailed on the slides. In addition, we are especially excited to evaluate deucrictibant's potential to end the progression of HAE attack, which is highlighted by both patients and physicians as a first step to relieve attack. This endpoint was developed by Pharvaris' team with physicians and included in the core set of outcomes recommended by a panel of the international experts who participate to the AURORA consensus. The outcome of this assessment has the potential to show the rapid, treatment effects of deucrictibant IR, and support its best-in-class properties from other on-demand treatments.
The propensity score match analysis compared deucrictibant IR data from the RAPID-2 long-term extension study against standard of care on-demand treatments, including icatibant and the C1 inhibitors from a real-world mixed method study. Participants on deucrictibant IR experienced symptom relief as measured by PGIC, a little better, only about 1.1 hours, compared to approximately 2.4 hours that in the control treated with standard of care treatment. Importantly, over 98% of the attacks studied in the long-term extension study achieved the symptom relief within 12 hours of deucrictibant use. With the rapid onset of symptom relief and the severity reduction, ultimately, people living with HAE want their attacks to be resolved completely and rapidly with a single dose of treatment.
In the RAPID-2 long-term extension study, with over 200 attacks treated with deucrictibant, time to median attack resolution was about 11.5 hours. Over 85% attacks achieved this symptom relief within 24 hours. Over 90% of them only required a single dose of deucrictibant. With this encouraging data, the team is dedicated to continue the pivotal study of deucrictibant IR capsule for the on-demand treatment of HAE attacks. We hope deucrictibant IR can be the new treatment to combine injectable-like efficacy and oral convenience that Dr. Tachdjian highlighted in his discussion of current unmet medical needs. Now, we will move to the prophylactic program. We once again are encouraged by our Phase 2 data, demonstrating deucrictibant's great potential to provide injectable-like efficacy with the convenience of a daily oral tablet for the prophylactic treatment of HAE attacks.
The latest outputs from the long-term extension of CHAPTER-1 study show that attack reduction is maintained, even further continuous improved with over one year deucrictibant prophylactic treatment. Compared to the baseline, 93% attack reduction is observed in the extension study. A medium attack rate of zero for every month is observed for up to 18 months, and the patients have 99% days symptom-free during the study. This sustained attack reduction is based on the twice-daily dosing of deucrictibant immediate-release capsule. Its PK profile is shown by the dark blue dotted line in the graph. In the pivotal prophylactic CHAPTER-3 study, we will use deucrictibant extended-release XR tablet. Its PK profile is overlapped with a green curve on the graph.
As shown there, with optimized peak trough ratio of extended-release tablet, it is expected more consistent deucrictibant coverage and the protection of patients from attacks. Meanwhile, once daily dosing regimen with extended-release tablet can further improve the convenience and adherence of deucrictibant treatment as long-term prophylaxis. Now the CHAPTER-3 study is on track to be initiated by the end of this year. We plan to enroll about 81 patients globally for a 24-week treatment period, with a 2-to-1 active to placebo ratio. Currently, we do not provide a specific timeline for data readout yet, but plan to provide further guidance as we continue the study move forward. In addition to the hereditary angioedema, deucrictibant has also been evaluated in two investigator-initiated study, POP-H and ONCE-H, for the treatment of acquired angioedema due to C1 deficiency. All these patients have underlying diseases and experience angioedema attacks.
There are no treatments approved for this indication yet. In both POP-H and ONCE-H studies, despite of small sample size, deucrictibant is very well tolerated and shows almost 100% attack reduction. In the ONCE-H extension study, deucrictibant extended-release tablets are used by acquired angioedema patients for over one year now. We're excited to see that XR tablets are well tolerated and protect the patients very well from attacks, as shown in the graph. In addition to almost complete attack reduction, it also demonstrate that the deucrictibant significantly improve the patient's quality of life. The encouraging outcome of extended-release tablets from ONCE-H study further enhance our confidence for CHAPTER-3 study in HAE. In summary, we believe deucrictibant's injectable-like efficacy, well-tolerated profile, and oral convenience positioned to be a potential best-in-class therapy for patients with HAE and potentially maybe other bradykinin-mediated disease.
team is dedicatedly to progress the development of deucrictibant for both prophylactic and on-demand treatments for people living with HAE. We will be presenting seven posters at the American College of Allergy, Asthma, and Immunology annual meeting this weekend in Boston. The posters from this meeting will be made available on our investor website tomorrow around 8:00 A.M. Eastern Time. With that, I will now hand it over to our Chief Commercial Officer to discuss the HAE market. Wim?
Thank you, Peng. Based on deucrictibant's profile and the clinical data to date, we have the ambition to become the market leader in HAE, and believe that deucrictibant has the potential to become the preferred option to treat and prevent HAE attacks. First, we intend to become the standard of care for on-demand treatment, as we believe that deucrictibant, thanks to its rapid onset and complete attack resolution with one single oral capsule, has the potential to become the preferred on-demand therapy. However, as you heard before, the desire of the HAE community is really to have no attacks at all, and people having a normal life. That is only possible with a preventive strategy, and for that, we're developing deucrictibant XR. Based on its injectable-like efficacy, we believe deucrictibant has the potential to lead the oral market.
However, we remain convinced that people living with HAE and are on prophylaxis today would, when given the option, opt for an oral product that can offer the same efficacy as an injectable, with the extra benefit of day one attack protection in the convenient form of an oral administration. Rather than managing HAE or the disease, a daily oral tablet has the potential to give them more control over the condition. Therefore, our ultimate goal in HAE is to become the product of choice for LTP overall. Finally, having the ability to switch from on-demand to prophylaxis and back with the same active ingredient and just a change in formulation, could provide patients and clinicians with the flexibility and confidence to manage HAE in the way they prefer through the different phases of their life. That is a unique feature for this investigational therapy.
With this strategy, we believe we can bring an option to people with HAE, desiring the convenience of an oral therapy with injectable-like efficacy and placebo-like tolerability. As you see from this chart, we expect significant growth in the HAE market over the next decades, driven by increased efficacy and convenience of new therapies in development. Prophylaxis is expected to continue to dominate this market, but also in on-demand, the advent of oral therapies will allow people with HAE to treat more attacks sooner and grow the market. We also believe that being first to market does not guarantee long-term market leadership. As you can see from the two charts on this slide, whenever two therapies with a distinct value proposition entered the market, whether it was a Kalbitor in on-demand or Takhzyro or Haegarda in prophylaxis, they were able to become either market leader or drive significant uptake.
Even today, with no recent new market entries, up to 5% of the U.S. patient population actively switches every quarter. This switching pattern was explained in some recently conducted market research with HCPs and people living with HAE in the U.S. As you can see from this slide: Are there obstacles like access concerns? Doctors, in general, feel quite comfortable switching patients, whether they're on prophylaxis or on-demand. Consistent with prior research, the doctor's choice for a prophylactic therapy is primarily driven by efficacy. However, people living with HAE have an outspoken preference for an oral therapy and are proactively asking their doctor for such an option. But half of them are seeking guidance from their doctor, and just a small proportion prefer an injection.
That's why we believe that oral therapy with injectable-like efficacy has the potential not only to become a first-line prophylactic option, but also market leader in this setting. Similarly, for people living with HAE, efficacy is what matters most, whether for on-demand or prophylaxis. We know in practice, though, as stated before, that an oral option is very attractive. Therefore, an oral therapy with injectable-like efficacy has the potential to really become their preferred choice. Now, speaking about efficacy, despite the relatively high level of compliance across all the long-term prophylactic therapies, people on prophylaxis still experience nearly three breakthrough attacks per year, and each and every time such an event happens, that provides an obvious opportunity for either the doctor or the patient to consider trying another therapy.
As we've heard from the doctors Manning and Tachdjian, people living with HAE are seeking a life that is not defined by their condition, nor burdened by its management. We believe that deucrictibant, thanks to its clinical profile, with the ability to provide injectable-like efficacy with the convenience of an oral therapy for both prevention and treatment of HAE attacks, has the potential to deliver on the expectation of the community and become the market leader in HAE. But that's not where it ends. Pharvaris wants to go beyond that. We have aspirations beyond type one and type two HAE, with the potential to provide benefit to people with any bradykinin-mediated angioedemas, such as acquired angioedema due to C1 inhibitor deficiency, as Peng showed you, as well as hereditary angioedema with normal C1 and beyond. But that's for the future.
With that, for the time being, I'd like to hand it back over to Berndt.
Thank you, Wim. Well, first, and foremost, I'd like to thank Dr. Manning and Dr. Tachdjian for delivering two outstanding, highly informative presentations. Obviously, the HAE treatment landscape has its unique set of physicians, and patients' dynamics, and hopefully, today's call helped our audience to gain a deeper understanding of the current unmet need facing people living with HAE. We're obviously quite pleased with the clinical data for deucrictibant and its differentiated profile. We also believe the results from our physician and patient surveys, they appear to be in alignment, with our view of the current treatment landscape and the product development strategy for deucrictibant. All of us at Pharvaris will remain fully engaged with the HAE community, and we continue to build strong connections with thought leaders and patient advocacy groups to fully understand the needs of the, this unique patient population.
We're incredibly excited about our work, as well as the opportunity in front of us to deliver improved treatment options for people living with HAE. With that, I'll now open the call up for Q&A.
Thanks, Berndt. So as mentioned, we'll be going to Q&A right now. Please hold for a brief moment while we poll for questions. So our first question comes from Laura Chico at Wedbush. Please go ahead, Laura.
Good morning. Thank you very much for the presentation, and appreciate the commentary here. I have one for Dr. Manning and then one for the Pharvaris team. For Dr. Manning, out of curiosity, what proportion of your prophylactic patients under care right now, do have a prescribed on-demand treatment? And then for Pharvaris, I believe CSL received a CRL for garadacimab in the prophy setting. Just any thoughts on potential ramifications for your own development efforts and/or commercialization? Thank you.
For my question, we work on following the guidelines that are out there, and so all my long-term prophylactic patients, they all have an on-demand therapy available. We strive for two doses. Now, it's prescribed. Will they all fill it all the time? I can't guarantee that. Will they use it? Many times they don't because the on-demand therapies right now are not necessarily favorable in an administrative role, and they may say, "You know, unless it's a laryngeal attack, I'm not gonna treat my foot or even my stomach because the administration of the on-demand therapy is worse than the attack that I'm dealing with, unless it's up in my face and throat." So all my long-term prophylactic patients will have an on-demand therapy available to them.
Yeah. Thank you, Dr. Manning, and the. Hi, Laura, and thanks for the question. So regarding CSL, of course, we can't comment on their specific situation there, but, as far as Pharvaris is concerned, of course, it highlights the importance of CMC in any drug development process, and we are doing everything also to cover everything in the progression towards the ultimate filing, also including anything that's related to CMC. And as we said many times before, also, we have all the supplies and already with the XR formulation for the clinical trials and drug supply, and.
So from our perspective, you know, we're obviously not directly affected by the CSL's topic here, but we are working on our program and covering all the bases as best we can.
Thank you.
Thanks for the questions, Laura. Our next question comes from Maxwell Skor at Morgan Stanley. Please go ahead, Maxwell.
Great. Thank you. I also have two questions. First one for Dr. Manning: could you please walk us through your experience prescribing Orladeyo? What type of patients are you starting on the oral treatment? Which patients are switching, and what do you think is the remaining unmet need for the prophylactic treatment of HAE? And then for Pharvaris management, can you provide any additional details regarding the FDA's feedback on the extended-release formulation? And just remind us why it wasn't used in CHAPTER-2 , and the work that went in to give you confidence to start it for the CHAPTER-3 trial. Thank you.
So the patients who are on Orladeyo in our practice, they initially kinda came from the studies. We were part of their development program and the studies. Many patients who enrolled in those studies were actually on long-term prophylaxis rolling into the study. That kinda spoke to them wanting a different administrative route or administration, you know, route of administration. So they were looking for an oral agent. Of those patients that were enrolled in the studies, many did very well. They were happy with the results, and they elected to stay with Orladeyo as the study wrapped up, and it became a commercialized product.
When I get a new patient now or a patient that comes to me maybe on another long-term prophylaxis, or maybe they're on on-demand therapy only, I have an open conversation with them, and we call it kinda shared decision-making, and so we will lay out the different products that are available, kinda talk through where their attacks are, how frequent the attacks are. If they're using on-demand therapy, does it take, you know, just one dose to treat it, or are they taking multiple doses to treat any given attack? How does it impact their life and their quality of life? Do they go to the ER, et cetera, and then we talk about each of the different long-term prophylactic options that are available. We will kinda delve into the efficacy data.
We'll talk about the safety data, the administration route that they're doing, and kinda put it out to them, saying, "Okay, here's what's available to you. What would you like to do?" We won't let them make a bad choice, but it's hard to know what's the right choice in this. There's no way to kinda really do personalized medicine with these individuals, so they may start with one. If they don't see the attack resolution frequency that they're looking for, or if they're having side effects that are intolerable, then we will switch. If somebody's already on a long-term prophylactic, they may come into us saying, "Hey, I heard about product X." It's a very connected community of patients.
They know what's being done in research, and when a new product comes to market, they're already aware of it, most of them. So they may come in and ask us about it. Again, we'll have an open decision about it, and they may say, "You know, I'm doing what I'm doing right now, I'm doing well. I don't wanna switch. I don't wanna rock the boat." If it seems to them to be more favorable to their lifestyle, the way they want to administer a drug, et cetera, they will ask to switch, and if we don't see any contraindication with that, we'll go ahead and switch them, knowing they can always go backwards if they need to. It's difficult to just change products in and out, because it's not like walking down to Walgreens and handing them a prescription.
It takes effort. It takes getting authorization, so it's a little bit of labor of love on our part to make those switches, but we'll always do that for them. We also want them to stay with a product long enough to make sure it's gonna work if they're not having untoward side effects. As you see the research data, these products tend to get better and better the longer you stay with it. Kinda for what I said before, I think they get comfortable. They're feeling better. There's less stress in their life. They're having less reactions. Therefore, their frequency of monthly attacks is going down, and they do better. So it's an open discussion with them. There's no one patient that we say, "You're not an Orladeyo patient," or, "You're not a lanadelumab patient," et cetera.
Patients of all phenotypes, whether it's frequent attacker, a rare attacker, a peripheral attacker, a GI attacker, they all respond to all the different products. It's just finding what works best for them.
Thank you, Dr. Manning, and hello, Max. I'll answer your other question on the extended release. As we were moving through our development, getting into the clinic with our program, and we started with the softgel capsule, and also then in order to maintain momentum, we developed the other formulation, extended release, in parallel. As we developed our product strategy, there were two products with the same active ingredient as we just discussed in the presentation. So that's just simply a timing issue, and we have. I asked Peng to comment on the regulatory interaction with respect to XR and also data that we've seen in including the PK data that you also saw in the slides. Peng?
Yes, thanks, Berndt, and Max, that's a great question. As Berndt mentioned, we indeed, you know, have really set a great assessment and also development for the extended-release tablet and also submit all available data to the agency. We also aligned with the FDA fully set to apply the extended-release tablet, 40 milligrams, that's the once-daily dose regimen for our pivotal, that's a prophylactic Phase 3 study, CHAPTER-3 study, which we will initiate soon this year. That's the short answer for your question. We've already fully aligned with the agency about using the extended-release formulation for our future development and, you know, for the next step, the Phase 3 studies.
... Great. Thank you.
Thanks for the questions, Max. So our next question comes from Joe Schwartz at Leerink. Please go ahead, Joe.
Great. Thanks so much for taking my questions. I have one for the company and one for Dr. Manning. So I was wondering if management could give us an update on enrollment and site activation in the RAPIDe-3 study, and any color on the patients that are going into this trial. Are they simply those that, you know, tend to churn off of other therapies? Are there patients that are actively seeking deucrictibant as a, as an on-demand option? And can you learn anything about, you know, what market uptake might ultimately be based on the willingness to participate in RAPIDe-3? And then for Dr. Manning, we've got really exciting innovation across the board in HAE, including CRISPR options perhaps soon.
I was wondering, you know, if you can give us any insight into the psyche of your patients and, you know, how many patients would you think would reasonably want to do something like that versus quote, unquote, "Just, you know, reach for a pill," if and hopefully when deucrictibant's available as an alternative to something as invasive as that?
Okay, so maybe I'll start then, Joe. Hi, Joe. Good. Thanks for joining the call here. So yeah, regarding RAPIDe-3, as we said, initiated in March, and the enrollment to date is fully in line with our expectations. It's going well. And we also think that, of course, with the data that we saw in our RAPIDe-1, the Phase 2 study, and the increased visibility of our HAE program in general also may be a factor that contributes to enrollment. The study design as such is also designed to give the opportunity of every patient that enrolls to try the drug, so it's a crossover design.
I'll hand over also to Peng to talk more about the color of the patients. They can get some color on what type of patients coming into the trial and how we see enrollment on that part so far. Over to you, Peng.
Yes, thanks, Berndt. That, I would like to echo that, the comments from Berndt there. Currently, our RAPIDe-3 study, the enrollment move well. That, as Berndt highlighted, is, consistent our projection and as planned that, initially that we start the study. And regarding the patient population, that because as Dr. Manning and also Dr. Tachdjian highlighted, that, you know, that on-demand treatment are needed for all HAE patients, no matter the, you know, the only on-demand treatment or prophylactic patients. Therefore, for our RAPIDe-3 study, we target, and also currently is enrolling, that are both on-demand patients and also patients on the prophylactic treatment. We would like to just, as you know, that the highlight in the study assess that the efficacy and the safety of the deucrictibant XR, that, you know, formulation for treating both acute attack and breakthrough attack.
So the question to me on kind of the psyche of the patients and the new innovations that are coming along, you know, HAE. It's a rare condition. It's 1 in 50,000, so for every 1 million people, there are 20 patients technically out there. So any given office may have 1 or 2 patients for the most part. Some people don't even see it, and most doctors will never see it, or they see it and don't know what they're looking at. But in our office, we have probably anywhere from 60 to 80 patients that we have active all the time because we do research. We have done research with every product that's already approved, and we're involved in all the research that's ongoing, including some of the forays into genetic options. There was one that was starting up.
We never enrolled anybody, and that study closed, so I think for a variety of reasons, and now the latest is a CRISPR technology that you mentioned. Started out in Europe first, it's coming to the U.S., and we've put this out to our patients, and we've got several patients who are very on board looking at something that may be a potential permanent solution. That's the hope for something like that. Some of these patients tend to be younger because they're looking for a lifetime of improvement, and they may have seen their grandmother and their mother deal with this. And so I think the way they approach the problem is a little bit different 'cause they've seen it last for years in those individuals. That's not every patient's looking at that.
I think there's still some hesitancy, and over the last four years, unfortunately, with vaccination issues and misinformation, etc., and you know, genetic manipulation, etc., there's a lot of fear of that, and so I think that may drive some of these individuals to either go away from it or never want to consider it. The psyche of HAE patients runs the gamut from people who are on the oldest of ages, the androgens, and just will not quit because they're too afraid to wean off and have an attack, to a lot of patients who are constantly looking for the next best thing, and they're always keeping their hand out for studies and looking to enroll in another study for a variety of reasons, but they're always looking for something that's easier, better, safer, less burdensome.
And may actually give them the ability to dose less frequency, less frequently, or in the role of genetic potential, you know, something that may be a potential cure. Don't know where that's going, so I don't have any data on that, but not every patient's gonna look for that. It's not the end-all be-all. All HA patients are not gonna jump to that. The patient who attacks infrequently, yeah, an oral agent that's on demand, works quickly, one dose, that's an easy fix, I think, for those patients. The other thing to think about is HA changes. So, the frequency can change over time. It really ramps up around puberty, gets worse.
You can be somebody who attacks once every three months, and all of a sudden, now you're having two or three attacks a month, and maybe down the road it changes again and becomes less frequent. It's not a stagnant disease. There's a lot of factors from hormonal issues to outside issues that affect how this affects individuals. Some patients are very on board looking at the future of genetic potential, and others want to maintain something that kind of tried and true and safe, and doesn't mess with their underlying kinda genetic makeup. I don't know if that answers the question, but we got patients who are looking at anything and everything.
Very helpful. Thanks for the color.
Thank you for the questions, Joe. So our next question comes from Catherine Okoukoni at JMP Securities. Please go ahead, Catherine.
Hi. Thank you for taking my questions. I have two for Dr. Manning. One on the acute setting and laryngeal attacks. What proportion of attacks actually involve the larynx? And how do patients and clinicians feel about giving an oral on-demand therapy for these attacks? And then my second question is in the prophylactic setting, and just what is the threshold that's usually used as far as monthly attacks go to say that a patient is not getting good enough control on a medication? And at what point do you usually kind of pull the plug on one medication and switch to another? Thanks.
Looking at the first in laryngeal attacks, I mean, we say that 50% of all HAE patients will have a laryngeal attack at some point in their life. Some people have frequent laryngeal attacks, and some people will never have a laryngeal attack. I think it's actually a higher proportion of patients who will have a laryngeal attack when you look at a lot of data and studies. When you look at some of the studies that were ongoing, you know, 75% of the patients enrolled in the study will have had a laryngeal attack in the past. I think it's somewhere between 50% and 80% of patients will have a laryngeal attack at some point.
I think even with earlier studies, with the IV ones that we did and the sub-Q ones, et cetera, sometimes laryngeal attacks in those studies were not treated as a blinded, you know, a placebo-controlled attack because there was a fear that, you know, giving them placebo, it's gonna put them at risk. And so anybody who came in with a laryngeal attack was just treated open label, so they were given active drug that we knew that would work. All the medicines we use, if it's gonna work for a foot attack or a stomach attack, it's gonna work for a laryngeal attack.
And with these newer oral agents we're looking at out on the market, their PK data, how quickly it you know gets absorbed and reaches kind of a threshold of being effective is really really good and as good as injectable stuff. So I don't have a fear of treating a laryngeal attack with an oral agent. I think sometimes there's you know can they swallow it? That may depend on what's going on. We preach treating an attack early. I don't care what treatment option you have is an on-demand therapy. If you wait long enough, it's gonna struggle to do anything, if nothing at all. Because when all the horses get out of the barn, and getting them back in the barn is really difficult.
The sooner they know an attack is coming, and they can treat it, the better it's gonna work. Now, when we look at an oral agent, especially if you think, "Gosh, my throat's kinda swelling," I take an oral agent right away, it's gonna work right away. I think that attack's gonna be interrupted quickly. I think patients have a mindset of, "If I'm popping a pill, it's a lot easier than an IV or an injection for that acute attack." I think they will treat earlier in the course than waiting, especially some of the injectable medicines that really hurt. These patients kinda wait and wait and wait and wait to make sure, "Yeah, that really is an HAE attack. It's not anything else." Now, it's six or seven hours down the road, and they give themselves the injection and get partial response, probably have to redose.
So I think that's one of the mindsets with an oral agent is, "I can treat early. It's easy. It's gonna work. You know, I can always take another dose if I need to, another pill versus an injection. Or if it's not even HAE attack, kinda no harm, no foul." From a prophylactic standpoint on what is considered a threshold of efficacy, it really depends on what was going on before that. It's one thing to say a patient has an attack a month that they treat. They may have three attacks a month that they don't treat and are minor.
And so we really have to dig into them and kind of pull that information out and say, "Okay, how about, are you having GI attacks that are just mild enough that you just kinda deal with it for a day and a half and don't do anything?" Well, we wanna fix those also. May not be that severe, but we'd like to shut them all down. So early on prophylaxis, you want them to be having two or three attacks a month to do an IV every three days.
Now with, you know, a pill that may be easy to take once a day or an injection that's every couple of weeks, it's easier to look at somebody with a moderate severe attack once a month to say, "Let's put you on prophylaxis, and not just treat that with on-demand therapy." But the key is also teasing out, you're probably having more attacks than what you think. And as they learn about it, and we talk to them, they may find out that, you know, "Oh, yeah, these little GI things I have periodically, that's an attack. And maybe that headache I'm having, that, quote, migraine is an HA attack," which it can be. So the more we get into them and talk to them, they may be more frequent than what they thought, and prophylaxis is very good. Is it working or not?
It's a discussion again. We have to talk to them about, "Okay, how often are you having an attack? How often are you having an attack that you're treating?" Again, we wanna know all attacks, and is, you know, the treatment burden worth what you're doing? And so what's acceptable to one patient may not be for another, and vice versa. So they're long conversations. They're not easy patients to take care of. They all have my cell phone number, and I think most of us who do research and treat HA patients, they've all got our cell phone 'cause they will text us and call us whenever, and we can help manage what's going on. If I start a patient, I want them to try to stay with the product several months before we pull the plug on it.
If we can, unless it's just unbearable side effects, they're having so many breakthrough attacks, we've gotta do something different. So I know it's probably not a black and white answer. There's no black and white answers in this condition. So it's a lot of discussion, a lot of feel, and talking to the patient, seeing what is working for them and what's acceptable. But we don't wanna just ask them, "How are you doing?" "I'm doing okay." That doesn't tell me anything. "How are you doing? What are you doing? Are you worried about your next attack? Is it limiting what you're doing? Are you not taking a trip? Are you not going to that wedding for fear of an attack? Are you not traveling to Europe, et cetera?" That's impactful, and that's impacting their lives, and we wanna fix that.
Hope that answered the question.
Yes, thank you so much.
Great. Thanks for the questions, Catherine. So I'm gonna chime in here with a question from an audience member on the webcast, and Wim, this one's for you. How do you plan to compete against LT injectables?
Long-acting injectables. Thank you for the question. What we've seen from our data, from the interactions we have with the community, is that there's not gonna be an answer, one answer for everyone. But if you have the option to have an oral administration, the same efficacy as an injection, even if it's a low-frequency injection, it tends to have a great appeal to patients because it's convenient, it doesn't hurt, as Dr. Manning said before, they might not feel as sick as when they get an injection. Our anticipation is that the prophylactic market will fall out in an oral segment and in an injectable segment. The oral segment, based on the insight we have, is probably gonna be dominating because it is the first-line option that you would try.
You tell me, "Take an injection every six months, every four months." I'd rather take an oral, even if there is a so-called convenience associated with less frequent injections. So the assumption is there's gonna be a dominance in the oral segment, and we feel very strongly that we can compete with the long-acting injectables. Within the long-acting injectables, there will also be a trade-off between the different players. Some are on a monthly, a two-monthly, maybe a three-monthly basis, and our anticipation is that we'll see kind of a winner also in that segment. But we're definitely confident. We definitely feel confident about leading the game there with the orals in long-term prophylaxis.
Great. Thanks, Wim. So our next question comes from Fanyi Zhong at Oppenheimer. Please go ahead.
Thanks, Maggie. I have two questions for Dr. Manning. This is Fanyi, for Jeff from Oppenheimer. So one question: How frequent are the dose missing from oral prophylactic treatment, by your observation, Dr. Manning, and the feedback by patients? How did that impact efficacy? And secondly, curious what % of the patient under your practice treated, switching from oral to other subcut or IV treatment for the potential better efficacy, and how much preparation are naive, HAE patients for oral treatment? Thank you.
I think I understood the first part of the question, so the frequency of oral administration is, did I get that right, once a day?
How often are people skipping, and how does that affect-
Oh, how often are they skipping? Didn't hear that.
Yeah.
So, you know, don't know. Lots of times patients are always looking for using less. They're minimalist, which I understand that, but I think most of the patients who are on the one oral therapy that we have right now, they're not skipping. They're doing well with it. You know, compliance is always an issue with any condition that we treat. But I think most of those patients, if they're doing well, they kinda don't wanna rock the boat because they've been bad before, and you know, they're really trying to normalize their life, and so they tend to be very, very consistent with dosing. If they miss a dose here or there, it's not a big deal. They may forget...
I think the patients who are on injectable therapy will tend to try to stretch the dose more versus the oral agents. They will try to push and not do the injection as often, or if they're doing subcutaneous administration, they'll try to push that out. IVs specifically will try to go less and less. But you know, the half-life of those, they kind of wean out, so you're kind of playing with fire with that standpoint. And the second part of the question was?
Switch behavior.
Oh, switch behavior. That's right. So, you know, the oral long-term prophylaxis was the last LTP to come out, so it was more switching from injectable stuff to oral, to be honest, was the initial approach, because patients were looking for an oral option. We still have patients that will want to switch from an injectable for a variety of reasons to oral. They wanna try the oral agent. Those that are on the oral agent will switch back only if they're not doing well. If they perceive they're not having the benefit they're looking for, or the oral option that's out there right now does have some GI side effects. It tends to go away over time if they can stay with it long enough, but there are some people that it's just...
It doesn't, and they just wanna switch and go back because they're just having too many GI side effects. It's a rare complication that lasts longer than about four weeks, but that does come up. I think the biggest reason to switch back from oral back to an injectable long-term prophylaxis is just the perceived or lack of efficacy. The data with the oral probably not quite, the oral prophylaxis out there right now is not quite as strong early in the early months of treatment versus the injectable stuff. The patient that does well and stays with it, just like some of these other ones, their efficacy and effectiveness improves over time as long as they stay with it. So it's just finding that right fit for that person.
Like I said, there's no phenotype of these patients that makes us think that you're a good oral candidate or you're a better injectable candidate. The one thing we will look at right now with long-term prophylaxis is kind of the pregnancy patients or the patients that are childbearing potential. We may keep towards a C1 product just because, in our mind, that's a safer way to go, because it's natural. We're giving the enzyme back that they're missing, so it's kinda natural from that standpoint, but that's a very small subset of the population. So if they're on another prophylaxis, they may... and they're deciding to have children, we may switch to that. And then once they deliver and stop nursing, we'll switch them back. So...
Thank you so much.
Great. Thank you for the questions, Fanyi. So our next question comes from Sushila Hernandez at Kempen. Please go ahead.
Yes, thank you for taking my question. I have a question for Dr. Manning as well, a bit more specific on all the developments in the prophylactic space. So how do you look at injectable options that are being developed, with the potential of dosing every three to six months versus an oral daily in terms of the treatment burden? And then a question for the Pharvaris team, perhaps I missed this, but could you elaborate on the final steps needed before the start of the CHAPTER-3 study? Thank you.
So, yeah, there's ongoing development with injectable, long-term prophylactic options that are out there, where instead of, you know, right now, what we've got is if it's a subq injection with C1, it's every three to four days. If it's the injectable, kallikrein antagonist, it's every two weeks, potentially every four weeks, if they're well controlled. Newer agents being looked at are looked at every four weeks. There are some that are looking at three, maybe even six-month data, or dosing intervals. I think those longer intervals on injection will affect the injectable therapy that has shorter intervals. I think patients will then gravitate towards that.
I think if somebody has the option and idea and their preferred route of administration is oral, just because you have an injection that may be three or six months, and that's all theoretical right now, I don't think that will dissuade them from taking an oral agent, because that's kind of what their mindset is, and that may fit their lifestyle. Like I say, if they're traveling and going about and they wanna keep something in their pocket, they don't want to use a syringe, they can be needle phobic. All these things are self-administered, and some people just will not give themselves a shot, period, plain and simple. Self-administration may be that their spouse, their kid, their grandmother, their neighbor can give them themselves a shot, but still, that's a burden of administration at that point.
I think some of those injectable potential for long-term injectable things that have a very drawn-out dosing interval may have impacted some of the genetic studies that were being looked at. I don't think it's gonna change the oral market, because I think people who are looking for a pill are gonna gravitate towards that. Just like in the asthma market, we've got biologics that are injectable, and I've got some asthmatics that we look at them in our office and say, "You need to be on one of these biologics because you're bad enough," and they flat out refuse, and they would rather stay and use oral steroids to rescue themselves out. We know it's not the right thing to do, but they will just not go to an injectable.
I think that's gonna be the same in the HAE market. There are some people that will just, for a variety of reasons, if they don't have to do an injection, they will not do an injection, even if it's just every six months.
Thank you, Dr. Manning. Hi, Sushila, this is Berndt. Answering about Chapter 3. We are in the final phases of wrapping up for the initiation of the first site. As we have guided, we anticipate initiating the Chapter 3 prophylaxis then around the end of the year. There's nothing specific there on any critical path. This is basically in execution mode, and the team is working firing on all cylinders to make that happen, and so moving things ahead.
Okay, thank you for the color.
Great. Thank you, Sushila. So our next question comes from Tazeen Ahmad at Bank of America. Please go ahead, Tazeen.
Hi, good morning. Can you hear me?
Yes, we can.
Okay, great. For the doctors, I maybe wanted to ask a little bit of a refined question to some of the previous ones, which is, by the time you get experience using this product in the on-demand setting, do you think when it becomes available for prophylaxis, you would naturally recommend that all the patients who have had experience with the drug for acute treatment automatically start taking prophylaxis?
So if the product comes out for short-term, for on-demand therapy first, let's say, and the long-term prophylaxis studies are wrapping up, they don't have approval for that, they're using it and doing quite well. When it comes out for long-term prophylaxis, I think patients who are already taking it and do well with it and know how well it works, they tolerate it, I think they would be an easy fit to go to long-term prophylaxis using the product. They may not need to. They may be somebody who's dosing their short-term, their on-demand therapy once every couple of months, and they're just gonna stay with that.
If they were using this as a rescue drug, and they were already on another long-term prophylaxis, let's say, and then this drug came out for long-term prophylaxis, it'd be definitely a conversation I'd have with the patient saying, "Hey, you're on this. You know, your on-demand is now a long-term prophylaxis. You can really use both. They've got two different formulations, one that's a sustained release or extended release, and one that's, you know, rapid release," and see what they wanna do. It would be a conversation. So I would always bring it up to them, whether they switch or not. You know, we don't have... We've not had anything like that yet.
Mm-hmm.
We've used some on-demand therapy for prophylaxis, off-label, but that would be the only way you really look at this, but I would look at this as, as different than that. So not sure I'd know how to predict. I bet you they would look at that. They may have already been on another oral prophylactic agent, and then using this as an oral on-demand therapy. And I can see patients who really like oral stuff, they're gonna look for an oral prophylaxis and on-demand to pair together because that's what they're doing, versus an injectable and an oral, but I could be wrong. But I think people who've had experience with it, patients who've had experience with it, patients who've been in the trials, we've been part of the trials, of...
When they do well in trial, they wanna stick with what they were doing in the trial, and when it comes to market, they wanna stay with it.
Okay, and maybe a follow-up to that. Based on what your use of on-demand therapies is today and taking into account current and future potential prophylactic therapies, do you think that the market for acute therapies will, in general, remain sized the same, or get bigger, or contract?
So will the market for acute therapy stay the same or increase? I think an on-demand oral agent is going to be very well received by our patients because right now, you've got two IV options and an injectable option that hurts. So they're looking for something better, and when I've talked to patients about, you know, what's coming down the pike and rescue drugs that are coming down the pike, they're extremely excited. I can see the oral on-demand market having the lion's share of that marketplace. The long-term prophy market, that'll is yet to shake out, I think, when we see it. So that just depends, but I see the on-demand oral market taking off.
That may impact a little bit long-term prophylaxis in my book. If somebody was attacking once a month, and they were using an injection twice a month to kinda prevent that, now they've got an oral agent they can pop, and it works really well in one dose, they may drop their injectable long-term prophylaxis and just treat on-demand, because it's easy, it's easy to redose, and like I say, there's a lot of needle fatigue, and so they would like to put the needle aside and probably just do an on-demand therapy for a little while. If they're having multiple attacks a month, then I think they're gonna wanna do something to prevent it. Because that psyche of, "When's my next attack? When's my next attack?
When's my next attack?" really is wearing on these individuals, and it actually, I think, creates more attacks from happening the more they worry about it, so if we can alleviate that, I think we're ahead of the game.
Okay. Got it. Thank you.
Thank you for the questions, Tazeen. So our final question comes from an audience member on the webcast, and this one's for you, Dr. Manning. What are the questions your patients are asking when they want to switch therapies?
So if a patient comes in and wants to switch therapies, they typically are asking about efficacy and side effects, how well it's gonna work for them. Like I say, it's a well-connected population, so they typically know what's out there and what's being studied, so they know when something's actually released also, sometimes before we do. And there was a long-term prophylaxis that was the FDA voted on a Thursday instead of a Friday, and she was watching the FDA website and emailed us Thursday night saying, "I want you to start the paperwork Friday morning." It's like, "Dude, I haven't don't have any paperwork. What are you talking about?" So they always kinda know what's going on. They've got friends who've been in studies. They may not have been able to get into a study, but they talk amongst themselves.
There are a lot of chat rooms, so they know what people are saying about it if they're in a study, and it kinda gets them excited. So, biggest thing is: Is it gonna work for me? And I think the next question is: Is it gonna be covered? Because these medicines aren't inexpensive. And the last thing is: If it doesn't work, can I go back? I think those are the questions we always ask. If the new thing doesn't work, can I go back to what I once was? And again, I have the conversation saying, "You know, we got to get it authorized. It's gonna take some work. There may be some step edits.
If we get it approved, and it's not working for you, to go back, we've got to then get that re-authorized and reapproved. And so there's ways we can switch, and sometimes we even have them switch before they've gotten rid of their old long-term prophylaxis. They put it on the shelf, 'cause then if we have to switch back, at least you've got some doses, you can start back on that, and while we're working on insurance authorization again. So, prior authorization for these things is one of the banes of our existence, but like I say, I've got an individual, that's all she does is that plus some other kinda, you know, specialized medicines, and so we're really good at getting what we want. A lot of that's gonna be educating the insurance companies, too, which we like to do.
Great. Thank you, Dr. Manning. So this concludes our Q&A session for today. I'll now turn it back over to Maggie for closing remarks.
Thank you all for joining us and dialing in to today's virtual investor event. And thanks for Doctors Manning and Tachdjian for joining us today as well. This concludes today's event. If you have any follow-up questions, please feel free to reach out to us directly. Thank you.