Guggenheim 3rd Annual Healthcare Innovation Conference - PHARVARIS NV

And thank you for joining Guggenheim's third annual Healthcare Innovations Conference. I am Devjit, one of the therapeutic analysts. And joining me on stage are Pang Liu, president, and Maggie Beller, the head of IR from Forvaris. Thank you both for making time for us. Thanks for having us. So who wants to take the first one? Maybe for people who have not heard the story, a very quick intro would be helpful, and then we can dive into the Q&A. Yeah, maybe I can start. I'm Peng Lu here. I'm the president of Favars. Actually, I'm a physician scientist. I've been working in HE over a decade. And always our motivation is how we can translate the novel science to really help the patients and really address what the patients need. That's exactly why we built up Favours here. For us, actually, it's a company really dedicated to developing oral treatment that for HE or maybe potentially Brett Kining, you know, mediate that patients there. Currently, we have our leading compound, the Ducritaban, and have one molecule with two different formulations. One formulation absorbed in upper GI and would be considered for on-demand treatment to help the HE patients. And the other is the prophylactic formulation, and to be considered for the prevention of the attacks for the HE or eventually for the blood kidney media angioedema patients. Currently, indeed, in the exciting moment for the company, and we are very closing to bring Ducritivine for our patients to give them greater control and simplicity here. Yep, and just a quick update across the business. We read out our pivotal phase three on-demand data in December of last year. We have a date for that on April 23rd, 2027. That will be for the on-domand treatment of HIV attacks. Additionally, we just read out our pivotal chapter three prophylactic data in September of this year. And we are on track to submit an NDA for that. As Pung mentioned, we're hoping to submit it for bradykinin-mediated angioedema because we're also going to be reading out top-line data from our CREATE study, which is the Ducryctabant for the Prevention of Acquired Angioedemia Attacks. That'll be in the first quarter of next year. So lots of really exciting things happening for Farvaris right now. So let's unpack that a little bit, the CREAT data. If that reads out positively, you are going to wait for that data before you submit the NDA for Ducryptoband XR, right? So the rate-limiting step for the NDIA is actually our open label extension data, the safety database from Chapter 4. It happens to be that the create data will align with our timing for the submission of the HAE NDA. So by combining the AAE data set with our HAE data set, we can actually apply for a broader label of bradykinin-mediated angiotema, and that may open us up to priority review. So that's what I was going to get at. How important are the CREAT data for a priority review versus a standard review? Yeah, maybe I can help address it. Currently, both our Chapter 4 study and CREATE study, as Maggie introduced on track here, that we expect we will move forward at a very simultaneous time. But as mentioned, there is no bonding together here that no matter for ATE or you know create that acquired angioedema study is we're discussing with the agency but as Maggie mentioned for the Ducretin especially for our prophylactic treatment that acquired patients they have no any treatment available from the whole community they have strong desire for the treatment available for them that's exactly we try all the best to give these patients that is a you know that available treatment as soon as possible. That's why we target to submit both HE and acquired angioedema in parallel at the same time. For Brad Cunningham, median angioedeema, the more broad umbrella term here. Got it. There is not much of a clinical debate right now, given that the chapter three had injectable-like efficacy for an oral product. How are you guys internally thinking about the commercial landscape, given this is a complicated, or not complicated, but It's a crowded commercial landscape, right? So how are you thinking about what could happen, say, 12 months from now? Actually, maybe I can start here. That's definitely, that currently, as mentioned, the next year is incredibly exciting for us. And the countries that we have built up, that is a commercial team, especially US commercial team. As I mentioned, there's a highly competitive field, but meanwhile, We have very strong team and I have said no matter for our R&D team and the commercial team have deep root in the aging field. Have very good connection with the whole community and also with the patient advocacy group here. Therefore, so far we are very proud, right? We have almost 80, 90% commercial team on board. And we are quite ready that to move towards, that the, you know, that get approval in U.S. that April next year and get a strong launch there. Maybe I can add a little bit just to the dynamics between some of the competitors in this space. So in the on-demand side of the business, we really feel that orals will dominate, seeing as you need to treat an attack after it happens to be able to address the signs and symptoms. the decreased treatment burden that one has when treating with an oral as opposed to an injectable is highly uh it highly prefers an oral because it's just easier to take it's more discreet the current injections sting when you have to inject them and one of the things that decryptobant brings to the table is that it utilizes the same mechanism of action as a catabant, which is the most widely used on-demand therapy right now. So what we view it as is a B2 receptor antagonist just like a catabamp, but this time oral. So that's really where we see the on-domand shaking out is that orals will dominate, and we have the benefit of the same mechanism. With prophylaxis, we think that there are likely going to be a winner in the oral space and a winner inthe injectable space. This is the benefitof having multiple therapies that are approved is that it can, each patient and physician can select what is best for that person's life. As you mentioned before, we're showing injectable-like efficacy. So for the first time, people aren't needing to make a decision between their efficacy, their tolerability, and their convenience. So somebody can prefer an oral or they may prefer an injectable, but now for the first time with our Chapter 3 data, they don't have to forego efficacy to have the convenience the world. Got it. So on the chapter three, when you think about the baseline, the attack rate was at baseline was relatively high compared to some of the other studies. When you look through your data, does the efficacy hold up across patients with higher baseline attack rates versus those with lower? Yeah, actually, that's a very interesting question that here that I understand that people ask us, right? Why is the baseline that attack rate is high 3.6, something like that? because for baseline actually there is a running period, it's a very short period compared to the general screening period in the past for phase two study. If we look at the other pivotal study as you look at it here, that no matter for the Donald Dorsen, or the MoZZ, or even Taxero around that time, all the baseline attack rate is around the same range. It's between 3.5 to 3.6 here. As I mentioned, if we look for the placebo group, that for the, you know, that chapter three study is also around two attack per month. It's very comparable, of course, that all the other that, you now, that pivotal trials. Therefore, overall, the chapter three, the patient segmentation is, I think, is a very, you knows, that quite, you known, similar to other pivotal trial there, and also, as Maggie mentioned, it's really reflect that the, you know the treatment, that for prophylactic treatment effect is comparable to injectable. Got it. Now, on the safety side, there were obviously those two patients with grade three liver enzyme elevations. It's pretty well explained, one with fatty liver disease, the other with prior anabolic treatment. How do you think FDA is going to handle those? Yeah, I can take it here. As Maggie mentioned here, that, you know, for the countries at the profit market here, right, that a patient really prefers the oral treatment with injectable light efficacy, but there is no sacrifice for safety part. As we always discussed here, that for the Ducretibone, no matter for the chapter one that we just published, our long-term safety data, and also the chapter three we just released here, Ducrotibone was very well tolerated. There are indeed tools at level two that liver enzyme elevation, we shared during the public, you know, top-line readout there. Actually, that for the HE patients, that due to the C1s, that, you now, serpine 1 gene mutation, C1 deficiency, that the patients have fragile liver. Therefore, liver enzyme elevations as a background to the disease there is not rare. Meanwhile, all these patients have that long-term, especially for international ex-US patients, They have long-term androgen use and also have the concomitant, for example, fatty liver and all the disease there. Therefore, we can tell almost for every prophylactic treatment trial there, there is a liver enzyme elevation reported. So do you have a sense of what percentage of patients in the United States are on danosol, if any, at this point, given all the options? And also on a fatty liver side, do we have a chance of what these numbers could be? From my exclusion perspective. Yeah currently is that a dinosaur use that in u.s Because all the modern therapy available is very low now pretty much I think less than 5% in US patients still on dental or use there is some patients use take on dental But the less and the less here but compared to international or ex-us this number is much higher Especially for example for the chapter 3 trial. We include the patients from Latin American countries from Asian Pacific countries this country's adenosine use is maybe still 20 to 30%. Got it. And beyond the two patients, the rest of the safety profile was clean, right? There are no other, call it grade 1, 2 liver enzyme elevations. Actually, I have to say that overall, that the liver enzymes, the lab abnormality part for the Chapter 3 trial is very comparable or within the range to other prophylactic treatments out there. I'd also add that one of the things we were really proud to see was very clean safety from a cardiovascular perspective and also from a GI side effect perspective. So those were two things that we were focused on because of just other discussions that have been going on in the KOL space and the other approved orals. we really wanted to make sure to demonstrate do correct demands generally well-tolerated profile, and we were happy to see that with the data across the board. And what do you need to see from the Chapter 4 safety database? And do you have insights into how that's playing out right now? Yes, that's typically very standard for all the HE treatment development. Typically, the agency would expect one-year safety data. That's exactly, as Maggie at the beginning mentioned, currently critical parts for our NDA filing for prophylaxis actually is the long-term safety package there. We expect we collect all the data, the first half of the 27 there, then we can submit the NDA filings for the prophy. Meanwhile, for the acquired angioedema, as we mentioned, they only need the ethics data because the safety data, we will leverage that is a safety package for HEE. That's the whole, that's our development strategy and the filing strategy. How we can use that as a parallel, that development here, that is the totality of package and the target for broader indication. Got it, so let's fast forward, call it 24 months from now, when both of these are in the market, what's the low-hanging fruit commercially? Is it the patients who are on Orladeo, given that's about a 47% response rate at best, do you try to switch those? Or are you going after Tuxero because of the injection site issues and all that, all the painful infusions? Yeah, actually, as Maggie have already mentioned here, that currently, I think no matter from the, you know, that Ordello or that, you know Act Early launch, they've already confirmed that the whole community desire for oral treatment. Therefore, I just say that I don't know whether it's a low-hanging fruit or not, but around that time, when we considered ducritabine, we really developed this treatment for all the HE patients who prefer oral, that options oral treatment with injectable-like efficacy. Therefore, as mentioned, typically we have designed that strategy for different segments of the patients, but meanwhile, we can tell, right, that for the new patient, it's definitely the patients that they will for oral treatment is easy for them to take and that you see that how about their treatment effect. Of course, the patients in the past use oral prophylaxis but not satisfied for efficacy or safety is also our target patient population. Or even current, that oral treatment patient, they maybe prefer that a better efficacy and or that injectable like the patients that they are tired of it and also consider oral treatment. All these, I have to say that the decree bond, hopefully, that can help them. Got it. With the IR approval coming up next year, are there any outstanding questions with respect to, with the FDA? And how do you think the label discussions are gonna shape up there? We haven't gotten into the details of how our regulatory interactions are proceeding. We've passed through our mid-cycle review And all of the activities that should and are happening are continuing to progress this plan. So we're really pleased with the engagements that we've had with regulators. For us, when we think about the label overall, we are really interested in having three key points included in the label. And how this exactly works out, we obviously need to wait and have discussions with regulators, but for us, we believe that Ducryptaban's differentiators include its rapid onset of action. So if that's demonstrated either through our primary endpoint of 1.28 hours or a new endpoint of end of progression that we included in our pivotal phase three, that is going to be an important aspect of our label. We also are really proud of our complete symptom resolution. As a reminder, we were able to show that endpoint in less than 12 hours. So the fact that 12 hours after taking Ducryptaban, people had no more signs of their HAE attack. And then the third really important aspect here is the single-dose resolution. So in our study, 83% of people were able to achieve their endpoint with a single dose of Ducryptaban. So those three key aspects, rapid onset of action, complete symptom resolution, and single- dose durability, are really important for us in the label. And however that ends up being built in, we have 11 key secondary endpoints that we achieved. So we're excited to have conversations with regulators about how we're able to demonstrate the differentiation of do correct to ban. So let's talk about that 83% of the patients having attack resolution with a single dose. Compare that with Ecterly. How is that conversation going with PEARS? Because that's an interesting item from a differentiation perspective commercially. Yeah, actually, that our, you know, that strength of the data, as Maggie just illustrated, and our initial interaction with the U.S. peers are very, you know, positive. I have to say that from the peer side, from the patient side, you can tell that the fast onset is definitely a key attribute. But meanwhile, from a peer perspective, that a high percentage of tech can treat it with a single dose is very attractive. especially compared to act early, right? It's around, I believe, that 38% or 39% of tech, they need the second dose, and even higher percentage of iCataban use a second dose here. If we integrate all together here, that from the peer perspective, you can see it's not only help the patients, but it can help economic side. Got it. So along those lines then, And do you think you would price it in line with where everybody else is? Or is there a premium to be had given the 83% or given the 17% versus 39% delta? So I think when we, it's premature to get into the nitty gritty details of our pricing strategy, but we're pleased to see that the pricing corridors within both on-demand and prophylaxis remain very compelling. For example, Ectorally right now is about 17,800 per dose. We, however, have the benefit of having an on-demand option and a prophylactic option. So instead of just looking at this and maximizing the cost of one singular asset, we are looking at the portfolio holistically and understanding the levers that need to be pushed or pulled to be able to maximize the value of the portfolio. So we have the benefit of having really strong clinical data and very proactive Payer engagements to be able to have those conversations to To be creative with our pricing strategy Absolutely as Maggie mentioned with the pipe You know We have pipeline within the molecule that we have both an on-demand and a profit discussion with the peers ongoing that they've definitely give us multiple options regarding the pricing part But meanwhile, fundamentally, I have to say our market-assessed strategy is to help patients can access Ducretivine as rapidly as possible, not only from pricing part, but also from, for example, the quick start sampling and also the contracting of the different strategy. That's the whole goal for our market assessed group. Got it. And currently, what is that, like 80% of the market is United States from global sales? value even. Yeah, from a global perspective. Absolutely. So what's the strategy for XUS for you guys? Yeah, XUS is definitely a very interesting topic and a lot of discussion with the country, all the geographic, right? That's a policy and the different factors. Currently, I think that our priority is the US launch and for both on demand and profit, but we do have a lot discussion for international and for Xus. that we also prioritize maybe in Japan and also the European countries. But currently, we don't have the details to share yet. But with the decreed by launch next year, we will gradually share more about our launch plan for international of XUS. Do you want to build an organization for XUS, or would this be a good non-dilutive funding opportunity for the company? These are options that are on the table right now. We haven't committed to an XUS strategy. But I think importantly, we are also not hindering our ability to be able to move forward with an Xus launch, whether it's by us, by a partner, or somebody else. Our MAA is validated and under review right now, we have a plan for other regulatory bodies throughout the globe, so we haven't commited to a strategy yet. Got it, and can you just walk me through your final head count on the commercial side as you sort of prepare for the launch next year and then the one year after? Yeah, currently as I mentioned at the beginning that we are almost there, that to wrap up that is a commercial team build up. And currently we target maybe very in line with the competitive data benchmark here. I believe we shared in the past that we targeted maybe 80% to 90%. 80 to 90 that are team members for US commercial teams, that's including also the medical there. We have pretty much 90% team ready on board. 30 to 40 of those people will likely be sales reps. And the number that you are sort of, or the allergists and physicians you're targeting is about 2,500 is from what I remember from my other companies. Yep, that's exactly right. Got it. Awesome, well, looking forward to a very compelling 2027 for you guys. And thank you for making time for us. Thanks so much, we really appreciate it. Appreciate it, thank you. Thanks, everyone.