Everyone, thank you for joining us. Our next session will be on the topic of UroGen Pharmaceuticals, and I have joining me on the stage, Liz Barrett, President and CEO. Thank you for being with us.
Thank you.
All right, let's kick off the conversation talking about a little bit of background. Can you walk us through your proprietary RTGel formulation and why it's particularly well suited to urothelial and bladder cancers?
Actually, it was the technology that was specifically developed for urothelial cancers because these urologists in Israel, the companies founded in Israel, just identified an unmet need to have medicines that could dwell longer in the cavity. Because the current standard of care today is just repetitive surgery, and the problem is when they try to deliver local medicines, they just get voided out very quickly. So they went about, you know, suggesting we need to find something that allows these medicines to stay longer. So this chemist in Israel designed RTGel, proprietary gel, and it's called RTGel because it's reverse-t hermal. So it's actually liquid when it's cold, but as it hits the warm temperature of the body, it turns to a gel, delivers medicine over a several-hour time period, and is voided out through natural urine flow.
So the urine actually breaks down, delivers the medicine, and then it's excreted from the body naturally. So that's why it works really well for urothelial cancers. It can also work in other parts of the body as long as there's an exit, you know, like for rectal cancer, esophageal cancer, colorectal cancer, those types of cancers.
That's a fascinating technology. And so your lead programs thus far have utilized RTGel impregnated with a mitomycin.
Yes.
And so can you talk to us about your decision to choose mitomycin initially to put into the gel?
Mitomycin was chosen because mitomycin actually gets used today, but in an aqueous formulation. So what happens is, and actually the guidelines in the U.S. also call for after surgery to use one, you know, dose of mitomycin in water. But again, the problem is it doesn't work very well. And so it actually doesn't get used much in the U.S. I think the peer-reviewed literature will tell you it gets used about 20% of the time. It does get used more outside of the U.S., but the benefit is about a 10%-15% incremental benefit. So we chose mitomycin because of the properties of mitomycin and because physicians are used to using mitomycin in the bladder. So it made a lot of sense, obviously, to use mitomycin.
There are a lot of times you'll hear about gemcitabine, but to be honest with you, mitomycin is actually a stronger chemotherapeutic agent than gemcitabine. So we chose, you know, mitomycin over gemcitabine.
Makes sense to me. All right, let's jump into your lead commercial product, JELMYTO. So this is your first commercial product. It was launched back in 2020, and it's a formulation of RTGel with mitomycin, and it's used in low-grade upper tract urothelial carcinoma. So can you talk to us about the treatment paradigm in that patient population and how JELMYTO fits in?
Yeah, no, absolutely. We did launch in 2020 right into COVID. I was like, you know, the world shut down, and May we launched in June. But these patients, again, for low-grade upper tract urothelial carcinoma, they get endoscopic ablation, which is similar to TURBT in bladder cancer, where they go in, they scrape out, you know, the tumors. Unfortunately, for the upper tract, about 50% of the time you can't even reach them because they're behind the kidney. So these patients, 70%-80% of the time, get their kidney removed. And it's usually either at time of presentation or after they've done three or four endoscopic ablations, you know, then the doctor will be like, "we have to take out the kidney."
Now remember that these patients are in their 70s and 80s. So losing a kidney and actually age is an independent predictor of reduced kidney function. So you're already taking, you know, a patient who's already, you know, starting to see reduced kidney function and taking away one of their kidneys. And so therefore an alternative was really important. And so we launched UTUC and actually even the FDA.
We had breakthrough designation. We had priority review because they recognized this sort of high unmet need. And so what's been happening is we've been growing our penetration in the market. You're seeing fewer patients get, you know, lose their kidney, although you still have physicians who are kind of what we call RNU loyalists. They still go in, they say, take out the kidney, then you're done. But a lot of patients don't want to lose their kidney. And so, you know, so they often, so we are working in between the space of endoscopic ablation and kidney removal.
You know, we continue to see, you know, new physicians treating all the time. The biggest challenge with the low-grade UTUC is it's a very rare disease. So it's such that there's about 10,000 urologists. There's 6,000 patients a year. So any one doctor may only see one or two patients a year. And so for them to remember and change practice, you know, has been a bit of a challenge for us, you know.
But the good news is, again, we continue to see new physicians using. Our patient demand last quarter, as we just reported, was very strong. And if we could just get that gross-to-net to stop declining, we would be in really good shape. But we're really happy with the quarter-over-quarter and year-over-year growth in patient demand.
Super. And I know that, you know, you're alluding to the size of the patient population and where this has been a drug on the market for several years. How do you at this point think about the total commercial opportunity for JELMYTO and kind of the peak sales potential in that patient population?
Yeah, we always used to say we're around $200 million. I don't want to go off of that just yet. I have, I think that when we launch UGN-102, you'll see, because we'll have more reps out there, you'll see that continue to increase. And again, as we've seen very strong demand, patient demand, we believe we can still have this sort of year-over-year double, you know, double-digit growth. And if we can maintain the gross-to-net at a reasonable, you know, number, then we should be able to hit that.
Perfect. And you started to allude to UGN-102, a s we think about moving forward with your other pipeline agents, what are the key learnings from JELMYTO and from your commercialization experience with JELMYTO that you're going to be leveraging for your subsequent programs?
Great question. And the big difference here is 6,000 patients, 80,000 patients. So what you're really, I think we underestimated two things with JELMYTO. We've learned that you have to be in the doctor's office when they're thinking about that patient. So the frequency in which you're at your high potential doctors needs to be more. So we've taken that learning and we've put that into our UGN-102 planning. Because originally we were talking, oh, we'll go from 42 reps to 60 reps, something like that. Now we're projecting 83 reps because we really want to make sure that in these high-volume physicians that we have the reach and frequency that we need. So that was one learning.
The second learning was UTUC is hard because you have to have fluoroscopy. So you have to have special equipment. Most offices don't carry a fluoroscopy. So you have to take them to the surgery center or to the hospital. So even though you don't have to put them under general anesthesia, it's still much more difficult. You're manipulating the upper tract and, or in some cases, the alternative dosing is they get a nephrostomy tube put in the back.
So you've got some doctors that like it one way and some that like it the other. We don't have those challenges with UGN-102. So that's the good news. It's very much an office-based procedure. You go in, you don't need special equipment. The catheter goes right into the bladder. You deliver it and the patient can go home. And it can even be done by a nurse. Not the case with JELMYTO.
So I think what we've learned is, look, make it, and we knew this, make it as easy as possible to fit seamlessly into the physician office. It's much easier to do that with UGN-102 than it is with JELMYTO. Again, you know, we just talked to a physician last week. We were talking to him about UGN-102 and he said, I don't use JELMYTO. And we're like, why? And he said, well, I only see one or two patients in a year. So I'm not thinking about it. I'm not going to change my practice. He said, with UGN-102, I see these patients every day.
And so it's a big difference, you know, when you're trying to get a physician to change the way they practice. When you're in there more often, they see more of these patients. It's much easier to make that shift than when they see one or two a year.
I know we're all really excited about the UGN-102 opportunity. A lot of investor focus has been on that program. Currently, UGN-102 is under review with the FDA for treatment of low-grade, intermediate-risk, non-muscle-invasive bladder cancer. So can you talk to us about the current landscape, treatment landscape for those patients at this time?
Yeah. Look, one, I think people are starting to understand bladder cancer a little bit better. This was actually when I joined the company five and a half years ago, was my first foray into bladder cancer. You know, I'd done almost every other cancer out there, and bladder cancer is very fragmented and segmented, so we are in low-grade, intermediate-risk, non-muscle-invasive bladder cancer. You hear a lot about other drugs that are in development, other drugs that are approved or in the high-grade space. Now you are seeing more and more of those in the high-grade space now starting studies in the low-grade, intermediate-risk space, so if approved, we'll be the first medicine approved.
I think the other difference for us is we actually, our data is without surgery, so our data is instead of surgery. When you look at the other, you know, medicines being studied right now, they're all in addition to surgery. So we feel like not only will we have several years advance, you know, and from a timing standpoint, you know, we'll be at minimally three to four years ahead of anybody else. So we'll have the opportunity, but we think we'll be the drug to beat, right? We'll be the medicine. I mean, it's hard when you've got our CR rate, you know, as we reported was in the high 70s. Our durability is around 80%. So that's the bar, right?
So, you know, I'm actually excited. People ask me all the time about competition. I think it's a great thing because you have more companies in there educating physicians on the benefit of doing something different than what they've been doing the way that they were trained. So the penetration of the market should grow. And so I'm actually excited about having, you know, more out there. When we first started talking about bladder cancer, even the FDA didn't understand low-grade doesn't really progress to high-grade and they're very much different segments.
Yeah, so true. And so up until now, you've reported some positive results from two phase III trials in UGN-102. There was the randomized ATLAS trial and the single-arm ENVISION trial. Can you walk us through some of the key clinical learnings from those trials?
Yeah, it was very exciting. The data when it came out, you know, so I can remember where I was when I got the phone call, you know, about the data on ATLAS. And the ATLAS data was the study, as you mentioned, which was the randomized study against TURBT. And I think that we as a company were overly conservative with how well we thought the TURBT arm would do. And we were very overly conservative about how well we thought we would do. And as it turns out, and look, there's other published data that also supports this. TURBT does not get 100%. You know, if you talk to a urologist, and I know we were talking earlier, you have your MD. If you talk to a urologist, a surgeon, they'll say, I get it 100% of the time.
Now, you know, the guy down the street, you know, he or she may not get it 100% of the time, but so to have the data that shows that even at three months, it's a 65% complete response rate. And we had, I mean, I was 65, there was a 64, so it showed it was really the first time that in a trial like that, it was demonstrated that TURBT is not 100% of the time or these patients actually quickly recur. So they had recurred within three months. But the important, most important piece of both ATLAS and ENVISION is around the durability. Because if you look at ATLAS was a combination of both newly diagnosed and recurrent patients. And so if you looked at that, you know, that data, you know, it was an 80% versus 50%.
If you looked at our ENVISION data, you know, we had an 80% durability at 12 months. When you look at the ATLAS data on TURBT, they're expected to, you know, 50% will recur within a year, and so being able to kind of see, and it goes down, by the way, for recurrent patients, so we know that after the TURBT from some data that we published, that every TURBT, the amount of time between recurrences reduces, which makes sense, right?
That's usually the case, so now we're looking at being able to extend the time between recurrences for these patients, and right now, our median time in the ATLAS wasn't reached, and we'll continue to follow the patients in ENVISION for five years so we can get to a median. But, you know, when 80% of your patients are still in, you know, that had a response, still a durable response at 12 months, that's a good number.
It's definitely encouraging. And so with your progress with UGN-102, you recently had your NDA accepted by the FDA and they set a PDUFA date for June of 2025. Can you talk to us about your confidence in the approvability of the program?
Yeah, I mean, look, first of all, I thought you were going to say I was disappointed we didn't get a priority review, right? I thought, I felt like we should have gotten a priority review. But the FDA and they've been very consistent. That's the good news. They consistently said there's an alternative. They get surgery today. So, you know, they weren't in any sort of rush. I mean, they didn't give us any feedback around that. But what they have been very consistent about is we have in writing that the study can be a basis for an approval, but it depends on clinically meaningful and totality of the data. So when you look at those things and they really focus on AEs and really focus on progression.
When you look at those, all of our studies, all of our data, it would be very difficult for them to say that 75%-80% CR and an 80%-85% durability is not clinically meaningful. I mean, that has, it's unprecedented. It's never been seen before, those types of numbers. So I don't see how they would, you know, could say that that's not clinically meaningful. I think the second part is around the adverse event profile. And in ATLAS, in all fairness, we actually had more adverse events than a TURBT did. But you have to look at the adverse events. They were all mild to moderate. They're what is typically expected in the urine, you know, in the urinary tract. And so these were, you know, again, mild to moderate, very, you know, everybody went back to normal.
We had two SAEs in the entire thing, and the FDA was also focused on progression, and if you look at our pooled database, it was 2.9% progression, and so really understanding that typically low-grade patients don't progress to high-grade, so you're not doing harm to these patients, and that was the big thing.
So I guess from our standpoint, you know, as a company, we have very, very high confidence in the approvability of the study. I've also been very clear that we're going to go to an ODAC because the FDA said you're changing practice. You're changing the way these patients are treated, so we want to talk to key stakeholders, so they want to hear from physicians that they want an alternative, you know, and so, and then lastly, I'll just say we also conducted a patient-reported outcome study in ENVISION and 90% of the patients preferred UGN-102.
These are patients that had been through a TURBT. There's a pretty big disconnect between what a physician thinks of a TURBT and what a patient thinks of a TURBT. So when you see that and you see that data, and that data will be published very soon, when you see that, and they will, we will present that at the ODAC and we will have patients there. When you hear from patients about what it's like after they go home from a TURBT and then you hear about what it's like after they get UGN-102 is significantly different. That's a story. We feel very, very confident in the approval and approvability. We're happy to go to an ODAC, frankly. We think that that's actually a good thing for us because we've done a lot of work.
A lot of our investors have done a lot of work. A lot of our partners have done a lot of work where they talk to doctors and doctors say, yeah, that, you know, he can criticize the way we did this study or this, but at the end of the day, do you want this to be approved? And the answer is yes.
Yeah, well, love to hear that confidence, and as you think about the potential approvability in the middle of next year, how are you preparing for the launch and the commercial opportunity that lies ahead?
Yep. The commercial team is in full swing. You know, like I said earlier, we will go, we started out with 42 reps for just JELMYTO. We're going to end up with 83 reps. We'll probably hold and have a bolus of a group of new reps, you know, right before launch, enough time for them to be, you know, ready and, you know, just from an expense standpoint. But we're doing a lot of, you know, pre-launch unmet need campaign. Our MSL is an important, you know, important factor at this point in time because they can actually be out there appropriately talking to doctors, appropriately talking to payers to make sure that we hit the ground running. I think the most important thing is reimbursement, right? It's a big deal. This is a buy-and-bill drug. It's an expensive drug.
From a physician standpoint, they want the confidence that they're going to get, you know, reimbursed. For the first six months, you're likely to see, as we do with JELMYTO, more use in the hospital setting than you see in the physician office. But as it moves and as we get our J code, you know, six months post-launch, you'll see that move to the office setting. Because, you know, that's where, frankly, you know, that's where physicians make their money, right? They'll make their money because the nurse can do this procedure. They'll make the money on the buy-and-bill. And it's better for patients. When you add all those up, it's a, you know, it's a good recipe.
Yeah. Sounds like a good recipe. And so one of the areas of consideration with this program and with JELMYTO as well is the IP.
Yes.
Currently it goes through 2031, but you recently provided us an update that you had a notice of allowance from the USPTO with potential extension of that patent cliff to 2041. Can you talk to us a little bit about your lifespan extension management program?
Sure. Absolutely. So when we actually, it's originally the initiative started as just manufacturing, right? We were looking for secondary manufacturer. It felt like it was a prudent thing to do. Our drugs, both JELMYTO and UGN-102, are complex manufacturing. It's a 20-day cycle. So we were really looking to see if we could find a secondary supplier. When we did, we found a company called medac based in Germany that has a proprietary formulation of mitomycin. And they already have patent protection to 2035. So we're like, great, you know, if we can do this. And so we did some experiments to make sure that it worked with a gel, but it is different. It is, as I said, a proprietary formulation.
So both the FDA said you can't just do a, there's no such thing as a bioequivalent study. You have to do a study. So we're like, okay, but that's also good news because that means no one else can come in and say, have a different formulation and just, you know, try to do some bioequivalence. And so because of that and the experiments that we did, we saw some different data coming out. And that's why when we filed for patent extension. And so now that they've, you know, notified us that we'll get patent protection to 2041, we were already in the process of doing our clinical study.
So the good news is we had a 240-patient study for UGN-102. We're doing an 87-patient study. So the FDA just wants to see, there wants to be enough patients to be able to see efficacy and safety similar to UGN-102. So that drug would be approved in 2027. And we would be able to take our current product off the market.
Now, somebody could come in in 2031, but, you know, they have to promote the product. There won't be any interchangeability or substitutability. Plus, we just talked about the challenges with the logistics. They would have to have, you know, a mixing partner, you know, a hub. And that's not, you know, the generic, you know, business model. So we feel pretty comfortable that even if somebody comes in, it'd be like a competitor. We'll have to compete with them face to face. There's nothing, no incentive for a physician to use their product, you know, over hours. So, you know, we really believe that, you know, the market will grow, you know, as CG Oncology, as J&J, you know, come into this space, that they'll, that we'll maintain our market leadership in this space.
We'll be able to, again, shift the business from UGN-102 to UGN-103 prior to 2031, to anybody coming in. And that's assuming they can make the drug and the gel. Because, as I said, you know, it's challenging. We've had many companies say that they've tried to develop and not been able to, so.
Interesting. And so the trial you were talking about is the phase III trial for UGN-103, which is the next gen of UGN-102. And so can you talk to us about the trial design and what kind of our timeline is to getting some data readout? What we would be looking for as well.
Sure.
Like what would be meaningful from that data?
Well, we already started the study and we made it exactly like ENVISION. And we did that because the fewer parameters that you change, the better, right? And, you know, there was a lot of more information we'd love to have, but we're going to have to do incremental studies for those. So anything we do from a lifecycle management, we're going to go into high-grade disease, but we're going to go into high-grade with 103, not with 102.
So as we do all those studies, so any lifecycle management we do, any studies we do will be done with the new formulation because obviously our patent protection is much longer there. And so, you know, from that standpoint, again, we will enroll in 2026, I mean, in 2025, we'll be fully enrolled. So we'll be able to, by the end of 2025, share CR data. So by the end of next year, we'll know what the Complete Response rate and then we'll follow those patients. And so we'll actually be able to file and get approval in 2027.
Okay. And that data you're expecting just needs to be as good as 102?
Yes. In the market, you know, I mean, in the range, right? It doesn't, I mean, what's in the range, you know, who knows, right? The FDA hasn't given us a number, but we expect that it just needs to be in the range.
Gotcha.
Right. I mean, if it was significantly worse, I can't imagine it being significantly better, you know, then we would have, we might have a challenge. But there's no reason to believe when you put the two together that, and based off of the experiments that we've done, you know, with models and everything, we don't expect it to be different. And actually there's, you know, there's benefits, right? And we're looking at all the other benefits that we'll be able to talk about.
But, you know, I talked about one of our biggest challenges is logistics and the mixing of the drug. This is a much easier drug to mix. So it takes less time for the pharmacy. So when you think about workflow and cost on the physician side and the hospital side, this will be less expensive for them and less time-consuming. There's a lot of benefits to both the physician and the office to use the new formulation.
Absolutely. With the time remaining, I'd like to just touch upon also your UGN-301 program.
Yes.
Which is RTGel impregnated with an anti-CTLA-4 antibody that you're pursuing in high-grade non-muscle-invasive bladder cancer. Can you just talk to us a little bit about that program?
Yeah, of course. We're in phase I right now. We actually have the data and we'll be sharing that at SUO this year in December on the monotherapy. But the intention was always that where we would really see the benefit would be in combination. So we also have our own proprietary TLR7 and we're doing it in combination with that as well as in combination with gemcitabine. And we'll have that combination data next year. And so for SUO, we'll be able to share, you know, our dose that we expect for phase two, any safety data. We obviously have done that.
And look, there's a lot of reason to believe if you think about other tumors, that a CTLA-4 checkpoint inhibitor in combination with either targeted therapy or chemotherapy will work. And so we'll start to share data of the combinations next year.
Super. We look forward to that. Thank you for being here today.
Thank you. Thanks a lot. Appreciate it.