All right, so welcome to this fireside chat with UroGen. I'm very pleased to welcome Liz Barrett, President and CEO of UroGen. Hi. Elizabeth, welcome. Thanks for joining us. Thank you. Thanks for having us. So Liz, before we jump into Q&A, just could you just briefly provide an introduction to UroGen and also the RTGel platform and your two commercial assets? Sure, of course. Our company was founded many years ago now in Israel, and it was actually founded based off of an unmet need by urologists to treat urothelial cancers. The concern or the sort of challenge with treating urothelial cancers is because when you deliver medicines to the urothelium, they just get voided out very quickly with urine flow. So, you know, physicians were, like, "How do we have medicines stay around longer in the bladder, and, in the urothelium?" And so these chemists in Israel actually got together and developed what we call our technology, RTGel. It's called RTGel because it's a reverse thermal gel, and it's liquid when it's cold, so when it hits the warm temperature of the body, it turns to a gel and acts as a depot, where it sustained-releases medicine over a several-hour time period. The great news about the technology is, in our experience so far, there's nothing we haven't been able to put into the gel. You do have to manipulate and sort of customize the gel depending on what the active is. And so, again, our company was founded off of this technology, and in our first two products, we use a well-known chemotherapeutic agent called mitomycin. So we take the mitomycin, combine it with the gel. It is instilled either to the upper tract for JELMYTO or to the bladder for ZUSDURI. And again, what it does is it dwells for several hours, enables the medicine to be delivered directly to the tumor, and kills the tumor cells before it's voided out naturally, you know, from the body. So it's an exciting time for us. We just got our second drug approved, and our first introduction in this space was for a small, rare disease, for low-grade upper tract urothelial carcinoma, so only 6,000 patients. Our most recent approval is for a much larger bladder cancer, low-grade intermediate-risk, and there's about 60,000 patients here in the U.S., so exciting time for our company. Great. Yes, so maybe then let's talk about ZUSDURI. There's been a lot of excitement around the approval last year, the launch that's ongoing, but maybe just stepping back again, just remind us of the unmet medical need in these intermediate-risk patients and how ZUSDURI is positioned to address it. Yeah, absolutely. So patients with non-muscle-invasive bladder cancer come in two flavors, or actually, they come in many, but two big ones: low-grade and high-grade. Within the low-grade space, there are patients that are identified as being intermediate-risk. That means they have multifocal disease, they have larger tumors, or they have a history of recurrence. This is a disease of recurrence. It's not a disease of progression. And I say that because it's very important as you think about how you treat these patients, that they're not going to die from their disease, and only a very small percentage ever even progress to high-grade non-muscle invasive bladder cancer, which is obviously a more urgent disease. So how do you treat. You obviously can't have tumors growing in your body, so even though they're low-grade, you have to treat these patients. Today, and for the last many, many, many years, there was only one way to treat these patients, and that was through surgical intervention of a TURBT, transurethral resection of the bladder tumor. So physicians go in, they cut out the tumor, and they cut out whatever, everything they can see. Patient, you know, is done. They, they sort of come back for surveillance, and typically, 50% of these patients will recur within the first year. And so you're in a situation where these patients never get out of that cycle of recurrence and never get out of the cycle of a repetitive TURBT, which is why there was such an unmet need here. And again, there has not been another way of treating these patients for many, many years. We're excited to be the first treatment in this space. Yeah to treat these patients. How should investors think about the overall market size in recurrent IR and MIBC? Yeah, there's about 60,000 newly diagnosed recurrent patients. I wanna be really clear. So there's about 20,000 recurrent newly diagnosed patients, but there's a large prevalent pool of these low-grade intermediate-risk, and in any given year, you've got about 60,000 of them that recur. That's our market. So our market, again, is low-grade intermediate-risk non-muscle invasive bladder cancer if you've had at least one recurrence. So about 60,000 patients, as I mentioned earlier. That's about 10 x the size of our first product that we launched, JELMYTO. And so it's a big market. It's a big market, and these patients, 68% of them have had two or more recurrences, 23% have had five or more recurrences. Yeah. Yeah, the product's now on the market Yes since last summer. We've seen, I think you reported 3Q results, 4Q obviously coming up. But, yeah, I mean, what can you share about how the launch has been going so far, perhaps prior to the approval of the permanent J-code? Right this January? Sure. You know, one of the, when we, when we actually announced our Q3 earnings, we only, we had just launched the product, and we only had about $1.8 million in revenue. At that time, we thought it was really important to share October revenue, which was $4.5 million, and the reason that we did that is because you saw one quarter at, you know, $2 million, about $2 million, but yet one month, you know, at 2.5 x the size. So that's why it was important to share that data. We don't typically do that, but the reason is because it takes time. There's a lot of time, you know, you think about drug launches, it's not a typical pill or an infusion. This is a procedure. So there are a lot of operational aspects of it that just take time, not only just P&T committee, but it's delivered through a specialty pharmacy I mean, a specialty distributor. It's a buy and bill drug, so you have all of these aspects that go along with the launch. So what we shared was that it takes 45-60 days between the time a patient is identified until they actually get the drug, and because of that, we thought it was really important to share that data. So we did, and I think the market was very pleased with where we were. And we kind of guided in Q4, because October was a strong month, that November, December would be similar, 'cause now you're coming into the holiday time period, and then you're coming on the end of the year, where we actually did have a permanent J-code. Right beginning January 1st. Right. And yeah, maybe talk about the initial experience, and feedback that you've received from physicians. We've had very positive feedback. Yeah from docs that we spoke with. Yes. Just in terms of how the therapy is being used perhaps relative to TURBT, which has been standard of care for so Yeah. No, it has been. I, I think everybody, physicians, patients, nurses, were excited and are excited to have an alternative for the first time. But importantly, the fact that the data speaks for itself, right? So we had an 80% complete response rate, and then 80% of those patients were still in response at 12 months. So we are rarely having a clinical conversation with doctors. They buy into the fact that from a clinical perspective, this is good. In addition to that, in our study, in our phase III study, we did patient-reported outcomes through UNC, and they did these independent surveys with patients, and 90% of patients said they preferred our treatment to doing a TURBT. So we've seen a lot of enthusiasm. To your point, I think you've heard it. I think we've also heard from a lot of our investors who do these physician calls that they're happy and excited about doing and enthusiastic about, you know, incorporating it into their practice. Yeah. Anything you can share on, I don't know, characteristics or what types of patients have been sort of the early adopters for the therapy? Oh, sure. And it's what you would expect in cancer, right? So typically, you start with your later lines of therapy, your heavily pretreated patients, and we're. And this is anecdotal, because we don't really track this information, but what we're hearing is that the three populations that they're using it initially, those patients that have multiple recurrences, those patients who recur very quickly. I'll give you an example. It was on our weekly call yesterday, and somebody shared that they had a patient, that one doctor had a patient that had had four TURBTs last year. So those, clearly, it's not working, right, for them. And then the third bucket is a group of patients, you know, the average age, median age, at the time of diagnosis is 74. You do have elderly patients that have comorbidities. That third patient population is those that they just don't want to put under general anesthesia again, take them back to the operating room. Yeah. Yeah. What percentage of the 60,000 patients would you say fall into this sort of high unmet medical need category? Yeah, I would, I would say about a third. Yeah. Yeah, yeah, because they're not mutually exclusive, but because between the three, about a third. Yeah. And then, you know, obviously, you do have the permanent J-code now, but I'm just curious, any feedback on reimbursement dynamics pre J-code, and then how that may have changed now that the J-code is in place? Yeah. The good news is that actually hasn't changed the actual reimbursement because we had 100% reimbursement even prior to getting the J-code. So reimbursement isn't really an issue as far as actually getting reimbursed, but everybody's worried about it, and so pre J-code, a lot of trepidation about using the medicine before they have a permanent J-code. You know, the things that you have to do, the actual paperwork is more intensive, it takes longer, but now that we have a permanent J-code, that should go much faster. But the good news is that we haven't had a denial yet. Right. We're seeing very, very positive feedback from a reimbursement standpoint. Makes sense. And then, obviously, a question a lot of investors are focused on is, with the J-code in place now in January, is there an inflection point in the launch curve? And, you know, what are you seeing? I don't know if you can share any early comments on how uptake has been since the J-code has been. Yeah, I will absolutely share that we are definitely seeing an acceleration. So I don't like to use the word inflection point necessarily, but it is an inflection point. The question is, is it a hockey stick? Is it linear? You know, what is the main, Still early, right, to tell, but absolutely seeing an acceleration across all of the parameters. You know, we look at patient enrollment forms and then how those patient enrollment forms transition to a new patient start, and how the new patient start then obviously transitions to doses used. And we are definitely very happy with where we are. We're on track with the expectations and our own internal expectations, and we are definitely seeing that acceleration. Okay. Then, a lot of us wonder, I mean, what is the realistic peak sales potential for Cysview, just considering the size of the opportunity and the early launch? Yeah, I think we can conservatively say that this is a billion-plus medicine, and the reason I say that is because we just talked about the 60,000 patients. It's about a net, you know, price of about $100,000. So if you sort of look at that, you really only need 20% penetration, 20% market share, to get to a $1.2 billion peak. So I think we feel very confident in that number, and believe that we can, you know, based on our own research, based on the enthusiasm that we're seeing in the marketplace to date, that we will definitely get there. Okay. There's been questions whether you might or might not be able to provide revenue guidance for this year. Yeah. at some point. So what is the, We're probably not going to provide, we did not when we launched JELMYTO. We will provide JELMYTO, obviously, guidance, but it's early, and so we need a few quarters under our belt before we're comfortable providing guidance. Right. And anything else that needs to be done in terms of post-marketing commitments from the FDA post-approval? The post-marketing commitments are really just us following these patients for five years, and we will provide those updates to the FDA. So every year, we have to provide an update on durability, which we want to do anyway, and which we want to share. And as I think everybody knows, you know, we talked about the 80% at one year, but we also have 72% of patients at two years are still in a complete response with our duration, a median duration of response not being reached. So that shows that it's going to be over two years for the median duration of response. That's very different than the conversation we were having earlier, where 50% of these patients that with a TURBT would have recurred within a year. Right. Right. How does that resonate with physicians that you market to? And, and maybe then related to, I know, maybe another launch question. So what are you seeing in terms of, dose, dosage use to rational therapy, and how do you expect it to evolve this year? Yeah. So we expect almost all patients will get all six doses. So we are seeing that happening. Like I said, we are rarely having a clinical discussion with a doctor. It's usually all around the operations, the financial pieces of it, because they get the benefit of it. And, you know, we've had some early, you know, feedback that they're seeing the complete responses, and that matters, too. So it's not just about what we tell them or what they saw in the clinical study, but now there have been enough patients that they've treated, that they're starting to see those successes on their own. So, you know, very, again, enthusiastic about the clinical data. And just as a reminder, this is without surgery, right? When you start to look at, you know, others in this space, we were the first ones and the only ones at this time to be doing a primary treatment. So a chemoablative treatment where you don't have to take this patient, Right into the operating room. Yeah, that's a good segue for my next question. There, you guys were first in class in intermediate-risk patients. There's a couple other companies, potentially coming into this space- Sure in conjunction with surgery, for example. How do you think ZUSDURI's position relative to a more of an adjuvant-type treatment paradigm? Yeah I, Look, we obviously know who all these, you know, other players are. You know, I'll start by saying I've been in oncology for 30 years, so I'm always happy when more medicines come. These are not cures. Patients need alternatives. Patients cycle through treatments, so you want more treatments for cancer to be out there. So I'm happy for that to happen. Not only that, but it also helps to grow the market. You know, we just talked about our billion-dollar peak is a 20% market share. There's still a lot of room for others to come in. You're changing physician practice. You're telling them, either use this medicine instead of or in addition to. It helps when you have multiple players talking about that. It helps to accelerate that adoption. Having said that, we really do believe we're the best treatment for patients and for physicians. So we talked about no need for a surgery, but the compelling 80% and 80% that they get. But one thing we haven't talked about is the number of installations. Six weeks, and you're done. So the data that we're sharing is no surgery, but in six weeks, and you're done. So when we think about being really patient-centric, you're not only talking about recurrence-free, but you're talking about treatment-free. If these patients can be in a situation where they can go two, three, four years with not only no recurrence, but they don't have to keep coming back for treatment, whereas all of the others that are coming in have maintenance in addition to surgery, their treatment, and then maintenance. So we think from the burden of administration, the burden it puts on the patient, the clinical data in and of itself, that all those things give us a very compelling, you know, argument for why use ZUSDURI over anyone else. Makes sense. Do you see a path for ZUSDURI in newly diagnosed patients, or will it always be a treatment for recurrence? No, I think we do. We absolutely want to move UGN-103, which is our next generation formulation, into both high-grade and into adjuvant. We're working on those study protocols, preparing for that right now. We will start at least one of those, maybe two of those studies this year, Mm-hmm second half of this year. And so one of the things that we're really committed to is investing in our company for the longer term, and we have a lot of opportunity. There are, you know, I talked about the two flavors, but there's actually many different types of, as you know, non-muscle invasive bladder cancer, and not all of them, you know, are treated equally. And so we think there's an opportunity for us across all of those patient populations. Makes sense. And then, yeah, maybe a follow-up question on, on UGN-103. You did report the UTOPIA study, Yes recently as well. And yeah, just remind us of your plans for that product in the intermediate risk setting. Yeah, absolutely. So we reported complete response rate. We're waiting on durability. We will have durability by kind of mid-year, our first cut at durability. We've spoken to the FDA. We will file the second half of this year, and the good news is that the FDA is allowing us to file without every patient being at 12 months, as long as we will update the filing during the review. So the plan now is we file this year, we get an approval in 2027, and we launch in 2028. The good news is, because of the patent availability there, we have patent protection through 2041. So that allows us to invest in UGN-103 across all of these other multiple patient populations. Makes sense. And then, yeah, maybe just touching briefly upon some of your earlier stage pipeline drugs. You have UGN-501, and then also UGN-104 in the works. So what can you tell us about those product candidates? So UGN-104 is very similar to UGN-103 in the sense of it's the next generation formulation for upper tract urothelial carcinoma, and we are right now enrolling in that study. That study should be fully enrolled this year, and we'll have the same strategy around 104 that we have around 103. UGN-501, I'm very excited about. It's our oncolytic virus. We think it's unique in the sense of, you know, not only does it elicit the immune response, but it also has direct cell kill. And we're right now been doing some preclinical experiments, and, you know, we compare that to, you know, others in the space and believe that we have a best-in-class, that it's a more powerful, you know, medicine to have. Not only does it work in bladder cancer, which is where we'll go first, not We'll do it initially alone, but then also have the ability to put it with our RTGel technology, and that should allow their even longer exposure. And then lastly, we'll be able to take UGN-501 into other cancers outside of urothelial cancers. So it allows our company, you know, for our company, we've always said we want to be a leader in urothelial and specialty cancers. So at some point, we'd like to diversify outside of urothelial cancers, and 501 gives us an opportunity to do that. Very exciting. And then, the question on JELMYTO. So JELMYTO is on the market for some time now. Yes. I think about $100 million Yeah per year in the U.S. How do you think about additional growth potential for JELMYTO, and are you seeing perhaps some, synergies, commercial synergies with the ZUSDURI launch? Yeah, we definitely have the commercial synergies from an expense standpoint. I do believe that there could potentially be this reverse halo for JELMYTO. We haven't seen it yet, but we do continue to see several things with JELMYTO. We see continued growth, you know, albeit low, so single-digit growth, but still continued growth, demand growth, you know, so we are seeing more patients being treated. We're seeing new treaters. So we're seeing new physicians that had not treated with JELMYTO now treating with JELMYTO. And what we heard from some of the physicians before was, "I only see one or two of these a year, so I'm not gonna change my practice." But now that they're getting experience with ZUSDURI, it's like, okay, well, then now I can incorporate JELMYTO at the same time I'm incorporating ZUSDURI. So we're hoping to see that, and we're calling now. We were calling. Our reps were covering about 5,500 doctors. Now we're covering 8,500 doctors. So just with that alone, you have an opportunity to continue to grow the base for JELMYTO, and then subsequently for UGN-104. So to your point, yeah, we've continued to see, you know, just kind of slow, steady growth, and I think that's what we expect, Right for the future as well. Yeah. How much overlap in ZUSDURI and JELMYTO prescribers have you had so far? Yeah. So I absolutely some of our early adopters of ZUSDURI were early adopters and big JELMYTO users. I think we've seen some, and, you know, we talk there's one, you know, group here in, in the New York City, that's treated 15 patients in ZUSDURI already. They buy into the approach. So they buy into the fact that using these medicines are gonna provide a longer, recurrent-free, treatment-free interval for my patients, both with JELMYTO and with ZUSDURI. So you definitely have your champions of the approach that we're taking. Get rid of, you know, get away from surgical in these patients, 'cause it's really not working, and use a different approach. So that's what we are seeing and how you can see the synergies when you see one and the other. They, you know, they really buy into the new way of treating these patients. Right, right. And then, yeah, just one last question. You did mention on 3Q earnings call. Yeah you did provide some visibility into October, so I've been getting the question on 4Q. I know. Will you give us some visibility to January, perhaps? No, we don't plan to do that. And, you know, we also, you know, JP Morgan, everybody said, "Well, why didn't you pre-announce?" We've never pre-announced, and we did that because we thought it was important at the beginning for everybody to understand what was happening with the dynamics of the launch if we had just gone out with 3Q. But I think we're comfortable and confident in, you know, our Q4 earnings and that we will share, and we will share as much color as we can. So while we won't give, you know, actual revenue numbers, we'll give enough color where people can feel confident of the acceleration that I talked about earlier, that we really are seeing that, as we come into the new year, despite the fact that January is a, You know, you start with rebate benefit verification and everything, that we are seeing that acceleration and expect to continue to see. So we'll give as much color as we can without giving the revenue number. Right. I was just joking, yeah, you should pre-announce that today here. I know exactly. Yes, I know we should, right? Absolutely. Well, we appreciate you having us here. Thank you. Thank you. Yeah. Well, well, thank you, Liz. Really appreciate it. So, good to talk to you today. Yeah, thanks. Thanks for providing all the insights. Of course. Thanks. Thank you.