Thank you for joining us for our next session. I'm Brittany Stopa with Guggenheim, and on stage with me is Liz Barrett, of UroGen Pharma. Thank you for being here, Liz.
Yeah, thank you. Good to see you.
So let's start off getting everybody up to date on the story of UroGen. So can you walk us through your proprietary RTGel formulation and why it's well-suited for urothelial and bladder cancers?
Yeah, absolutely. I always like to tell the story that, you know, they had a chemist and a urologist at a party having a conversation, which is actually true, believe it or not. But our gel was developed in Israel because urologists actually identified this unmet need. So with urothelial cancers, the treatment is really repetitive surgery. And the reason is because there aren't medicines that can dwell long enough in the cavity to actually be effective, because they get voided out very, you know, with urine, with urine flow. So typically what happens is, so they said, boy, it'd really be nice if we could figure out a way for medicines to be more effective. And so therefore these chemists actually started working on what we call RTGel. It's a reverse thermal gel, and it's a polymer-based gel.
It's actually called reverse thermal because it's liquid when it's cold, as it hits the warm, it gets mixed with the active. In the case of our first two products, it's mitomycin, a well-known chemotherapeutic agent. It gets mixed, and as it gets instilled into the body, as the body hits the body temperature, the warm body temperature, it turns to a gel. Then it sustained releases over a several-hour time period, and then it disintegrates with natural urine flow and gets voided from the body. It's a very elegant solution to what was a high unmet need and what still remains to be an unmet need. To your point, it was actually specifically designed for the urothelium and so to address, you know, the challenges with actually delivering medicine in that area.
It is always so powerful when a solution comes from the physician need.
Yes.
And to have them be part of the founding concept is so important. And you mentioned that the RTGel is impregnated with mitomycin. And what led you to choose that as the initial chemotherapy to work with?
Mitomycin is a well-known agent for urothelial cancer. So even though it actually isn't "approved" by the FDA, it gets used and has been used for many, many years in this space. So we chose that because we thought that was the most relevant for these types of cancers. And, you know, it works. It's, you know, it's worked in the past. Unfortunately, when aqueous solution, because it doesn't, it's not there long enough, it has a minimal effect. And so what we've been able to prove in this case is that it works very well. Interestingly enough, though, about our technology is we haven't yet found something we can't put in the gel. So not, you know, mitomycin's a small molecule, but we've also been able to put large molecules. We've been, you know, our, you know, anti-CTLA-4 that we have been able to put that in there.
We've actually even been able to put two drugs in the gel at one time. So there is a lot of flexibility for using it, not just in the urothelium, but in potentially other areas of the body.
Absolutely. Let's start to dive into your different programs. So JELMYTO is the first commercial product that UroGen launched back in 2020. And that's a formulation of RTGel with mitomycin, and that's for use in low-grade, upper tract urothelial carcinoma. So talk to us about the treatment paradigm in this setting and how JELMYTO has potentially influenced that treatment paradigm.
Yeah, absolutely. So these patients, it's really important to kind of understand the difference between low-grade and high-grade cancers and urothelial cancers. Low-grade cancers, low-grade histology, patients don't die from those diseases, but obviously tumors are growing in your body, and no one can keep tumors growing in their body. So typically they present with either blood in the urine. They find that they have most of actually the urothelial cancers are low-grade. And so you just have to manage the recurrence of low-grade. In the case of our upper tract product, unfortunately, these patients were actually losing their kidney most of the time. So about 70% of patients, either at presentation or after multiple endoscopic ablations, were losing their kidney. And so, you know, the reason I bring that up is low-grade.
So for a low-grade tumor that you're not going to die for, you're having to lose a kidney. That's a big deal, especially because these patients are elderly. The average age of diagnosis is around 74. So, you know, you have late 70s, early 80s that these patients are getting that. And we know that age alone is an independent prognostic factor of reduced kidney function. So you don't want to lose your kidney. At the end of the day, you don't want to lose your kidney. So we were able to sort of bring this to the market. And it's actually one of the reasons that the FDA, we got approval on one single-arm study with JELMYTO, is because they recognized this high unmet need of these patients losing their kidney.
So we've been, we've launched it, you know, and, you know, we're pleased that we continue to see growth, you know, year- over- year for JELMYTO. It is a procedure, so it's not a typical drug or infusion. So it is more of like a drug device. We sort of, you know, look at it from that perspective. And so there is, you know, you do have to have fluoroscopy, so you have to have special equipment. And so we are seeing physicians who adopt it and really believe in it, really, you know, really take ownership of it. Every quarter we see new physicians write. The interesting and probably the biggest challenge with the low-grade UTUC is there's only 6,000 cases a year, but they get treated by 10,000 urologists. So you don't really know where you're going to find that next patient.
So unlike our second drug that we hope to be bringing to market in June, you know, where everybody sees those patients, there's many more and about 10 times the number of patients in bladder as there are in UTUC. But we're pleased that we're able to bring an alternative to patients with UTUC and, you know, then be able to maintain their kidney.
That is so important. And you've recently highlighted some real-world data, some long-term follow-up studies from the real-world setting. So I wonder if you could share with us the key learnings from that and also how it compares to what you saw in the trials?
Yeah, absolutely. So for JELMYTO, very important, because obviously when we launched, we only had 12 months of data. These patients either, again, if they don't, you know, immediately lose their kidney, they go through what they call endoscopic ablation, where the physician goes in and basically cuts out the tumor. Unfortunately, the majority of those patients will have to do that every year because these tumors come back. What we were able to demonstrate in our study, our follow-on study, is that the median time to recurrence for our drug is four years, so almost 48 months. That was very compelling, and that's a very compelling argument for patients to want to see this versus having to have these repetitive surgeries or the alternative of losing their kidney. That was great data for us.
We've actually, we have a registry with JELMYTO, and with the registry, we're able to gain a lot of insights as to how the drugs could be used. And we're finding, again, that's where, you know, we're continuing to see that this recurrence-free survival is increased with our use of our drug. But, you know, some physicians use maintenance. We see that if they do use maintenance, they still have 100% recurrence-free survival. And so it's really giving us some good insight into how it's being used, no matter where in the kidney area they use it. So whether it's in the ureter or the pelvis, they are also seeing good response. So it's able to give us some good, to your point, real-world evidence, and it's actually better than, frankly, what we saw. It usually doesn't happen that way.
You usually don't see better results in the real world than you do in the study, but we're actually seeing better results in the real world.
It's certainly encouraging. And now that you're almost five years into the commercial experience with JELMYTO, I wonder how you think about the peak sales opportunity. Have we reached that? Have we plateaued? Like, how do you think about JELMYTO moving forward from here?
Yeah, I think what we've all talked about, and I think we see it and expect it will continue slow, steady growth. You know, we don't expect there to be a hockey stick. What I am excited about with UGN-102 for JELMYTO is we're doubling our sales force. So as I talked about before, because JELMYTO is a rare disease, being out there and being able to increase our reach and frequency, I think will help JELMYTO because you're there more often. So hopefully you'll be there whenever that patient presents. And so the representative will be able to talk to the physician about JELMYTO. And so I think that you'll see sort of a reverse halo on JELMYTO. So we haven't really talked about, you know, peak revenue. I would just say we expect to see slow, steady growth, you know, of JELMYTO.
So we by no means have met, you know, reached our peak. We expect to continue to grow. And I think as people, as physicians use UGN-102, a lot of them have said, "I'm not going to change my practice for one or two patients a year, but I'll change my practice for UGN-102." And so as they do that and they adopt that into their practice, I think they're more likely to also use JELMYTO.
Absolutely. So that's a perfect point for us to pivot into talking about UGN-102, which we know a lot of investor focus has been on that program, and so 102 is currently up for FDA review in the low-grade, intermediate-risk, non-muscle-invasive bladder cancer setting. That's a mouthful.
I know.
Talk to us about the current treatment landscape in this disease and how 102 will fit in.
Actually, it's very similar to what we've been talking about with Jelmyto. These patients go through a TURBT, a transurethral resection of the bladder tumor, where physicians go in, they cut out, you know, the tumors. What's interesting about that is actually I was able, when I first joined the company, to actually experience and be able to see one. I actually went with our Chief Medical Officer as he did a TURBT. And you, as you're cutting tumor, it's like getting, you know, harder and harder to see, right? It's clouding. So it's very difficult for physicians to be able to go in and ensure that they have gotten all of the tumor in there. So again, if you have intermediate risk, which is larger tumors, multifocal disease, or a history of recurrence, then you typically recur within a year.
So more than half of the patients will recur within a year. So these patients, elderly patient, going under general anesthesia, having to go in there and have these repetitive surgeries, that's the current standard of care, right? There's not much else, and there aren't any other medicines approved. So we would be the first drug-approved and medicine-approved for this patient population.
That is certainly exciting. And now the submission that you made to the FDA is based on two phase III trials. You had the randomized ATLAS trial and then the single-arm ENVISION trial. So what were the key clinical learnings from those trials?
Yeah, I think, look, the agency has said, and we agree, that ENVISION is our pivotal study and that ATLAS will be supportive. But ATLAS , we believe, brings a lot of very important and critical information because it was done against current standard of care TURBT. And so what it showed actually in ATLAS is that not only the complete response was the same, was very similar, but the duration and the durability. So for those patients who had UGN-102 or those patients who had TURBT, the duration of response was much greater for our drug than it was for TURBT. So we didn't actually reach the median, but we reached, we were able, we reached it for TURBT. So we actually demonstrated. I think that's our kind of key message is durability, right? Is really getting a duration of response.
These patients can have treatment-free intervals that, you know, they have recurrence-free survival. They don't have to worry all the time about their, you know, about it coming back. Even in a, we did a small study in our phase II where we did a follow-on study as well. Those patients also had very long durability. We, you know, see these diseases as being very similar. We expect very similar sort of responses. We've been really pleased with the results from ATLAS and ENVISION. For ENVISION , I like to coin the 80-80-90. You had an 80% complete response rate and 80% durability, and 90% of the patients preferred UGN-102. I think that that's important as you think about this as an alternative for these patients going through repetitive surgery.
These all the patients in ENVISION had had at least one TURBT. So they've experienced a TURBT, and now they've experienced UGN-102. And 90% of the patients preferred UGN-102. And I think that that's important. I think we don't talk about that enough, and because I don't know that everyone appreciates the impact that these repetitive surgeries have on a patient.
Yeah, absolutely. And I think that durability is key in providing clinical benefit that is meaningful to the patient.
Oh, absolutely.
And so the NDA for 102 was accepted by the FDA back in October, and they set a PDUFA date of June of this year. Can you talk to us about your confidence in the approvability of the program?
Yeah, we're actually, Mark sitting in the audience, our chief, he said, "You have to," we were actually talking about the fact that I'm going to have my first grandchild in this month, actually, hopefully in a couple of weeks. And I said, "But then I'm having a baby in June." So we feel very confident in our data. You know, like, you know, I've been in oncology for 30 plus years, and I've never seen data that has an 80% complete response rate and an 80% durability. So the questions that the FDA has raised is, is this clinically meaningful and the totality of the data? So I have a very difficult time even imagining that this is not clinically meaningful to anyone who looks at it, right? So I think we have a very high confidence.
We do know that, you know, the FDA has said we're going to an ODAC. We expect that ODAC in May. We feel very good about going to an ODAC because we believe that physicians and clinicians understand and appreciate the option that we're bringing for these patients. So we've been doing a lot of work around preparation for that, a lot of work around preparation for the commercial launch. So again, we have high confidence in our ability to be able to bring this medicine to patients.
Absolutely. And with the strength of data that you've demonstrated in these trials, I wonder what is your perspective on what you think the FDA will be asking about primarily, what will be their focus of the ODAC?
Yeah, they have told us, you know, when they accepted, they say, "Here are the three questions," right? And the three questions are, does ENVISION, which is our pivotal study, provide substantial evidence for approval? Two, what is the role of ATLAS? We talked about ATLAS . You know, we stopped ATLAS early. So the question is, what data from ATLAS is supportive and how do you use ATLAS and the supportive nature of the... And then the third is really around AEs, and it's around adverse events and, you know, comes down to risk-benefit. So have you demonstrated, has the company demonstrated a risk-benefit so that the benefit is worth the risk? And in our AE profile, I think it's really important. And in the beginning, when our conversations with the FDA, they were worried about progression. They were worried about adverse events around safety.
But that's a big part of what they, you know, they need to do. And what we've shown is that almost all of our AEs were mild to moderate. They resolved. There were only two serious adverse events in ENVISION that also resolved or are resolving. And so from that standpoint, we feel really good about kind of where we are. In the beginning, like I said, the FDA was focused on these patients' progress. We had a very low rate of progression. Even if you pulled all of our studies together, it's half of what you typically see. And so, you know, from that standpoint, I think we've been able to demonstrate that risk-benefit, right? And that the benefit is well worth the risk.
Remind us, what are the most common AEs that you encountered with...
It's really hematuria, you know, things that are around the urothelium. The only two serious AEs, one was retention, urinary retention, and the other was a stricture, which we saw a lot in JELMYTO, but you don't expect to see in UGN-102. It's really mostly around those types of things, which are very expected, frankly. You know, anytime you take instrumentation or you put mitomycin, it is a chemotherapeutic agent. You know, you're going to see some of this. The good news is we didn't see some of the things you typically see when you have infused mitomycin. We didn't see any of that. The good news is we know that physicians, particularly urologists, are used to dealing with these types of AEs. We're not concerned about it. We don't believe urologists are.
We think from, again, a benefit-risk perspective, it's better for the patient.
And you talked about some of the differences in the AEs between JELMYTO and 102. And part of the difference is where it's implanted or injected, where JELMYTO is put higher up in the urothelial tract. So have you noticed any upward migration of 102 once it's put into the bladder? Does any of it move up?
No, no, no, not at all. And you're right in the sense of, again, with JELMYTO, because you are going to the upper tract, you're manipulating the upper tract, which is why you need sort of special equipment to make sure that you're putting that chemotherapy in the right place. But you don't see that. You know, the bladder is very easily accessible. As a matter of fact, we expect that the majority of it will be given in the doctor's office, not even by a physician, you know, really by a nurse, you know, or a nurse practitioner, that the instillation will happen there. And so, you know, they put the catheter in, deliver the medicine, and the patient is able to go home, which is why we believe that patients prefer it.
What they said in the study that we did was less impact on their daily life, right? If you go in after TURBT, you're going home and you're going to bed. You know, they could leave their office visit. They said it took less time, stop at the grocery store on their way home, just go about their normal daily lives. So from that perspective, we feel like we, you know, offer a benefit for the patient.
Absolutely. So we're looking forward to that ODAC and the PDUFA date upcoming. So following that will be the commercial opportunity. So what is the commercial opportunity for 102 as you see it?
Great question. We sort of, I think we're so focused on the FDA approval, we forget what the big opportunity is. And really, you know, I think we love to make sure that we focus on the impact we're having on patients. But we have said that this opportunity, again, 10 times the opportunity that you see with JELMYTO, 80,000 patients, 20 of those newly diagnosed, 60,000 are recurrent patients. It's over a $5 billion-$6 billion market, right? And so we have publicly said we expect that UGN-102 will be a $1+ billion opportunity. So over a $1 billion opportunity. And so look, we're excited about it, you know, for our company. It's obviously transformative for our company. And, you know, we're happy to be able to, you know, forge new ground, frankly, in this area.
Absolutely. And so you've talked about TURBT being the standard of care. And so 102 would be the first kind of medicine approved for this patient population. We also know that other medicines are under development from competitors like J&J, CG Oncology, and LIPAC Oncology. So how do you see the competitive landscape for this patient population evolving?
Yeah, I always think it's people. My entire career when I've been in oncology, people have always talked about your competition. And in oncology, I look at it a little bit differently. First of all, these patients, they're not cures, right? So these, unfortunately, medicines aren't curing these patients. They're going to need multiple lines of therapy. I like the fact that more companies are coming out with medicines in this space. One, I think it will help to shift from these repetitive TURBTs to actually using alternatives and seeing being able to get, again, these longer treatment-free intervals for patients. So I think more companies out there talking about it actually helps because I think it grows the market. We will clearly be the leader. Everyone else is several years behind us.
So even if they come out, I think the other thing you have to keep in mind is that all of them so far are in addition to TURBT. And our drug is, you don't have to do a TURBT. So when you look at the results and when CG Oncology and J&J talk about the results of their studies, remember that is their drug in addition to TURBT. And our data that we've shared and, you know, really unprecedented data that we've seen is primary treatment. And so I think that's a big difference. I'm not sure everybody appreciates. So I'm happy for them to come, frankly, into our space. You know, we're happy to go into theirs as well. We expect to be moving into high-grade, you know, bladder cancer as well. But I think there's enough room and there's enough opportunity and patients need more medicines.
Definitely true. With the last few minutes that we have, let's talk about the rest of the pipeline. So I know that you have recently initiated and dosed the first patient in your phase III study of 103, which is the next-gen formulation of 102. So what distinguishes that formulation and where does that program stand?
Yeah, so UGN-103, which is the follow-on to 102, and UGN-104, which will be the follow-on to JELMYTO, are both a different formulation of mitomycin. So, you know, really we found it as we were looking for alternative manufacturers to ensure a supply. And we found this company in Germany called medac. And we're excited about the fact that that drug is easier to manufacture. It's been, you know, they actually also have, it's a proprietary formulation. So they had patent protection to 2035. It's easier to manufacture. It's easier to prepare. So we don't expect necessarily a difference in clinical benefit, but absolutely a difference in preparation. So it will take the pharmacy less time to prepare. It's more soluble. And so what we're doing in our plan is to do both of those studies to have, you know, the 103 study is almost exactly like Envision.
The same thing with 104 will be very similar to our Jelmyto study so that you'll be able to see the similarities and the differences. The expectation is that we'll be able to launch the follow-on UGN-103 in 2027, which is well, well ahead of our patent loss in 2031. We will put that drug on the market and we'll, you know, it will replace UGN-102. We were issued our new patents for that to 2041. We expect to be able to extend the franchise. We also expect to move UGN-103, as I mentioned, into high-grade disease. We're working on what that study looks like, what would the dosing look like for high-grade disease. We're, you know, have a lot of expectations for that moving forward.
Excellent. And you're also moving into the high-grade space with UGN-301, which is impregnated with the anti-CTLA-4 antibody. And that trial, you recently reported the monotherapy data at SUO. So can you talk to us about where that program stands?
Yeah, absolutely. So right now we're finalizing the combinations. All along, we've always said that we expect the benefit to be in combination therapy. We will be sharing data, I think, over the next few months around the combinations. We're starting to see that. We are seeing, even though it's a phase one mainly, you know, meant to find the dose for a phase II study, but we are seeing some efficacy data in that as well. So we'll be sharing that over the next few months. So again, you know, like you said, we have many shots on goal. We also are looking at other collaborations and, you know, can we take our gels we talked about earlier and combine it with other medicines for this space and be able to launch that.
You know, we're looking at a lot of ways to extend the franchise beyond where we are today.
Super. Well, thank you so much for your time and I appreciate it.
All right, nice to see you. Thank you.