Good afternoon, everyone, and welcome back to Cantor's Healthcare Conference. My name is Eric Schmidt. I'm one of the Tech Analysts at the firm, and it's my delight and pleasure to introduce our next presenting company, Fireside Chat with UroGen. We have my good friend, Liz Barrett, here, as well as another good friend, Mark Schoenberg.
Hi.
Liz is CEO, and Mark Schoenberg is a CMO, and we're gonna talk about urology. So Liz, maybe just give us the 64,000 sq ft view of the world and where UroGen is today.
Yeah, no, look, it's a great question. Nice to be here always, and great to see you, Eric. Thank you, everybody, for your interest in UroGen. Look, our company, I joined the company about five and a half years ago. When I joined the company, really learning about why the company became, you know, and that was because these urologists in Israel, because our company was founded and based in Israel, identified an unmet need in urologic cancers, and that is to deliver medicines to the urothelium. And unfortunately, the challenge is, is you just get voided out with urine, and so therefore, there were no options for these patients outside of these repetitive surgeries. And unfortunately, the diseases that we treat are highly recurrent diseases, and they are not curable.
So they continue to come back, and you're really talking about a patient population, that average age is about 74, and, you know, they don't really need to be going through multiple surgeries. And so because of that, they identified this unmet need, and these great chemists in Israel designed our technology called RTGel. It's called RTGel because it's a reverse thermal gel, because it's actually liquid when it's cold. As it hits the warm temperature of the body, it turns to a gel and sustained releases medicine over a several-hour time period, allowing the medicine to actually work in the organ in which it's in. In our case, like I said, for our first two products, low-grade urothelial cancer, both in the upper tract and in the bladder.
Okay, so that first product has now become JELMYTO?
JELMYTO.
And that's been commercialized now about four years?
Yes.
I think we're four years.
Mm-hmm.
Into launch. You mentioned it's approved for low-grade upper tract urothelial carcinoma. Just kinda lay out how big an opportunity that is for us.
Yeah, it's actually a rare disease, so there's only about 6,000 patients, about 3,000 newly diagnosed and about 3,000 recurrent patients a year. Unfortunately, unlike most rare diseases, it's not. It's very dispersed. What I mean by that is, there's actually 10,000 urologists in the United States. Any one doctor is going to see these patients. So trying to find these patients is small. If you looked at the entire market and said, "If I had every patient who had UTUC, both newly diagnosed," it would be about a $700 million market. Right now, our penetration is about, at about 12%.
Okay, and, what's gone well with the launch, or where is there an opportunity to do better and penetrate more than 12%?
Yeah, no, I look, if I said I was satisfied with 12%, I probably wouldn't be up here. We absolutely would love to see more patients have access to our medicine. I think, as I said, the biggest challenge is actually finding these patients because they're so dispersed, and you never know, you know, when any one urologist only sees one or two of these a year, and so finding them at the right time in a urologist. We actually believe that as we expand into our bladder, that we'll be able to find not only the bladder cancer patients, but that will help us. That was actually one of the learnings. It's a very high-touch sell, and so it's much more like a device sell than it is more like a traditional pharmaceutical, right? It's a procedure.
Unfortunately, you have to have fluoroscopy because you're manipulating the upper tract, so there's some complexities associated with it. So what we have learned is really around needing this sort of, what I call, surround sound with the customer. You really have to be there. You've got to be, i t's a high-touch situation, and you really have to to be there to help the physician in their practice. Otherwise, you get this, "Juice isn't worth the squeeze." So you've got to make it, you know, I always we talk about the Staples Easy Button, right? You always have to make it as easy as possible for a physician to integrate it into their practice.
Okay, so let's unpack that a little bit more. You know, when we talk about your next product, UGN-102, there are gonna be some similarities and maybe some differences to that market. But you're going to be going to urologists again.
Yes, yes.
You're going to be going with, you know, a semi-device type of sale again. On the other hand, what, just many more patients out there.
Yes, many more.
So you don't have to deal with the rare disease nature.
Correct.
Of the onesies and twosies. That's how you're thinking about it?
Yeah, that is, but also, maybe I'll ask Mark to talk about the differences between delivery of the upper tract versus the lower tract or the bladder, because that's the ease of use, now that we have very compelling data, which obviously we'll talk about in a moment, but just the usage and how the physician actually uses the product.
Sure. Thanks, Liz. So as everybody in this room knows, the kidneys are hidden up under your rib cage. They're hard to get to, and urologists have worked out all kinds of tricks to get little tubes up into the kidney, which is what we use to deliver JELMYTO, our first medication. So it requires some special technical expertise on the part of the physician. It requires the ability to use fluoroscopy to see where you are in relation to the kidney. There is some technical nuance to delivering our first product, and that you know has been a challenge that we've somewhat overcome by using something else called a nephrostomy tube, which is a tube placed directly through the back into the kidney to serve essentially as a port.
That said, you get the idea that this is a more complicated procedure than what we're going to use for UGN-102, which is the product for the bladder. This can be delivered through a urinary catheter that is placed in an office setting by a nurse, and the medicine is instilled through this urinary catheter. The catheter is removed, the patient gets up, gets dressed, and goes home. The entire procedure, we anticipate, will take 30-45 minutes max. So a much less technically complex, much easier, much more user-friendly delivery mechanism for our second product.
I think the other thing when we launched JELMYTO, you actually, from the time the drug was mixed with the gel, you only had eight hours to deliver it to the patient. Here, you're gonna have a week. So we have seven days once it's mixed, right? Obviously, much longer before it's mixed. We actually will do the mixing for the doctor and for the office if they want us to, and so when we deliver it, again, as Mark said, much easier, and won't even be done by the doctor, really be done by a nurse or an extender.
Okay, so many more patients and much, much less technically complex. But it is still urologists. Liz, you've launched a bunch of cancer drugs.
Right.
So tell me about why urologists are a little bit different or?
So, yeah. So to Eric's point, I spent the last 30 years in oncology, mostly and with oncologists instead of uro-oncologists, and there are differences, right? You know, oncologists, somebody will say, "You know, are you slow to adopt?" They'll say, "Well, I'm not an oncologist," because, you know, oncologists are known to adopt the latest treatments, the latest technology. Versus urologists, you know, if you look at how long did it take them to adopt the robot, right? It took them many, many years to adopt the robot. So they're much slower, I would say, in adoption, and when I was out actually talking to customers about a year ago, and they said: "Well, it's still new on the market." And I was like: "You're kidding, right?
It's been out for three years," and an oncologist would have already hit peak. So we have learned that urologists are much more conservative. Having said that, I think that the excitement of the data will overcome that, and the difference, and you also get. Urologists are surgeons. That's the other difference. So the big difference between oncologists. They're surgeons, and the standard of care today is surgery. So you're talking to surgeons to not do surgery and talking to them about not doing surgery. That's why the clinical conviction and the clinical data is so critically important, and I think that we have demonstrated in our clinical studies that we are offering the first-ever treatment available to these patients and that the data is really unprecedented.
Okay, so let's pivot to UGN-102, specifically, and before we get into the data, maybe, Mark, you can just walk us through the treatment paradigm in low-grade NMIBC and kind of the current standard of care.
Thanks. So, patients who have this disease typically present to their doctor with blood in the urine, and that prompts a referral to a urologist, and there's a very standard set of tests that are performed to make the diagnosis. The most important of which is looking in the bladder, a procedure called cystoscopy, and at that point, if a tumor is identified, the very next step in the management of that patient is to take the patient to the operating room and under anesthesia, use a different type of scope, with a small electrical knife on the end of it, to remove all visible evidence of cancer. That procedure is called a transurethral resection of the bladder tumor.
It goes by the acronym TURBT, and it is performed hundreds of thousands of times each year in the United States for exactly this indication. Patients, once they've been relieved of their tumor, either get hospitalized overnight if they're having problems with bleeding, or more often go home, and then come back to the office three months later to have their bladder inspected. Then they enter into a regular sequence of follow-up visits because these patients have a very high likelihood of recurrence. And if you look at all patients who have non-muscle invasive bladder cancer, the likelihood of recurrence for everybody is 70% at five years.
So if you have this disease, you are almost guaranteed to have another tumor in your lifetime, and the patients we're focused on have multiple recurrences throughout their life and have therefore multiple surgical procedures for their care, and that's one of the, we think, the opportunity and the unmet medical need that we're addressing with UGN-102.
How does that compare to high-grade? I know there are others in the space that are looking at that side of the market.
Sure. High-grade disease initially is treated the same way, and the procedure to remove the visible tumor provides the pathologist with tissue that can be evaluated under the microscope and then designated either as high grade, and as the name suggests, high grade means high risk of recurrence and even progression to a more advanced form of disease, or low grade, which is what we're focused on, which has a very low likelihood of progression, but a very high likelihood of recurrence, and it's really the recurrence problem that we're trying to address. High-grade disease, in addition to being treated with surgery, is also treated with adjuvant therapies, usually given in the bladder, and there's been a lot of activity in this area recently with the approval of a number of different drugs to address this.
Because the typical drug to treat high-grade disease is BCG, and as many of you may know, BCG is in short supply because of manufacturing problems.
So what, what's not ideal about TURBT for low-grade NMIBC? Why, why is that a current standard of care, unmet need?
I think historically, if you asked urologists what's wrong, they'd say nothing, because in fact, it's a relatively straightforward operation to do, and as Liz has pointed out, urologists all over the United States treat these patients with surgical therapy. Everybody learns how to do this in their residency. The problem is that the physician experience diverges pretty dramatically from the patient experience. This is a procedure that encumbers patients with a painful recovery that can last weeks. A certain percentage of patients will be hospitalized. There's some very predictable morbidity associated with TURBT, up to and including perforation of the bladder. The analogy I use when I talk to my residents about this is: It's an easy procedure. All you're doing is scraping out the inside of an egg without cracking the shell. No problem.
So it carries some risk, and the problem for our patient population is patients are elderly. The average age of diagnosis is 74 years, and they undergo multiple procedures. And as Liz has said on numerous occasions, we know from SEER data that 65% of patients have two tumors or more, and 23% of patients in the SEER database have five or more tumors. So you get the sense that these patients are just rotating through the operating room over and over again.
I think that's the biggest, you know, unmet need and why we need new treatments is really. A nd we picked specifically this intermediate risk, because if you have low-risk disease, TURBT works fine, right? You get a TURBT, you can usually, you know, last a long time. But these patients, you know, doctors call them frequent flyers. They come in often because they recur. And oh, by the way, the data that we've seen is the more recurrences, the shorter period of time between recurrences.
How do you define low-grade intermediate risk?
Yeah, Mark, why don't you?
So there's been an effort to try to risk stratify people so that we, physicians, could better manage different risk groups within the sort of broad swath of patients diagnosed with non-muscle invasive bladder cancer. So, professional organizations have defined intermediate risk as patients with new tumors that are greater than 3 cm in greatest dimension or multifocal tumors, or patients who have recurrent disease, typically within less than one year. So that panoply of characteristics defines the intermediate risk group.
I understand there's shortages with BCG today, but is that something that could be used in these patients going forward at some point in time?
Yeah. BCG has historically been used for high-grade disease and actually a very specific form of high-grade disease called carcinoma in situ, for which surgery is really particularly ineffective. It's used broadly in the American urologic community to treat various forms of high-grade disease. Since 2012 , when the BCG shortage became a real problem in the United States, our professional organization has recommended against using BCG in any group of patients other than those with high-grade and imperative indications, who are at risk for the development of muscle-invasive cancer. So for the foreseeable future, BCG is really not gonna be an option for the patients we're focused on.
But in theory, it's something that could happen over time if the supply constraints were lifted?
The one argument.
Yeah.
Yeah, the one argument against that, however, is that because of the relatively cold nature, immunologically, of low-grade tumors, immunotherapeutic strategies in this population may actually be less successful than in high-grade populations.
There's no data to inform BCG in that indication?
People have used it, you know, like they've used everything else, but in fact, there aren't big studies of low-grade disease in BCG.
There's no true study data, right?
Okay.
One way or the other.
Talking about true study data, maybe, Mark, if you'd like, you just walk us through the results of the ENVISION study.
Yeah. So the ENVISION study is the study that is the pivotal trial in our NDA submission that just went into the FDA for our request for approval for UGN-102, and it is a single-arm, open label trial of 240 patients who entered this international trial over a period of about a year who were treated primarily, and these are all patients with recurrent disease and who have disease at the time they enter therapy, with once weekly dosing of UGN-102. It was given in an office. They come in, they get a dose, they go home, they come back the next week. And then six weeks after the last dose was administered, these patients underwent an office cystoscopy.
This is looking in the bladder to see if there's presence of tumor, and 80% of these patients were free of disease at that three-month time point, which was the primary endpoint of the trial. In addition, because the durability of the effect of this therapy is very important therapeutically and also from a regulatory perspective for us, we followed these patients out for a minimum of 12 months before submitting our data to the FDA. And the durability of that complete response rate is approximately 80% as well. A little higher, actually. So it's kind of a remarkable result, and the piece of information to contrast with this that you ought to keep in mind is, a similar group of patients treated surgically would experience a 50% recurrence rate at a year.
This is a group of patients who had a 20% recurrence rate at a year. It is a markedly better result than we could achieve with our surgical standard of care contemporarily.
Okay, so 80% of the 80% were still in a CR 12 months later?
Correct.
How does the ATLAS study results support ENVISION?
The ATLAS study report. So we ran a randomized trial against surgery as another phase III trial, which we closed enrollment too early, but continued to follow patients after enrollment of 280 patients in an arm, either getting primary drug therapy or getting primary surgical therapy. Two supportive pieces of information: one, the control arm is very reflective of what we understand surgery can do for this patient population. In addition, the complete response rate in the ATLAS trial, admittedly, a slightly different population because it's a mixed group of new and recurrent patients, was 65%. And interestingly, the durability of that complete response was approximately 80% at a year as well. So very reflective of what we saw in the ENVISION trial. So directionally, very similar, and we've seen that across our clinical development program.
Okay. So, congrats on submitting the BLA. I'm sure that was a lot of work.
Yeah.
Expectations for review timelines in a panel?
Yeah, so we are hoping for and expecting, frankly, a priority review. We will know mid-October because at the 60 days from the time we filed, filed in, you know, mid-August, so we'll know. If we get, we have been pretty, we've been very transparent that the FDA in our pre-NDA meeting said, "You will likely go to an ODAC." So we are planning for an ODAC. We expect an ODAC. If we get a priority review, the timing would, for an approval, would be mid-February. If we get a standard review, it would be mid-June. We will know mid-October whether we have a priority or a standard review. So we're excited about that.
Look, you know, either way, it's good, you know, we're in preparation for launch, because either way, we'll be launching in just a few months.
What do you expect will be the key kind of questions at ODAC? Is it the early termination of ATLAS and the [crosstalk]?
No.
[crosstalk]
The FDA was very clear in our pre-NDA meeting. Two things, what they said. They said, "Because this is paradigm shifting, and you're doing something, you're treating these patients very differently than the way they're treated today, we wanna get stakeholder feedback because you're doing that, and then the second thing was really around progression and adverse events." Mark, you wanna talk a little bit about just the progression and their sort of comments about that?
Sure. One of the worries that the FDA expressed repeatedly was this concern that we would be delaying the standard care for this patient population, which would result potentially in progression to a more life-threatening form of disease. Now, we do know that the treated natural history of intermediate-risk disease, when it is low grade, is very indolent in the sense that there's a very low likelihood, even in surgically treated series, of progression to higher grade disease or higher stage disease. And if you look in the peer-reviewed literature, that rate is about 5%-15%, depending on study. Our pooled data show that the progression rate in our experience clinically with UGN-102 is 2.9%. So again, our data appear to be better than the available surgical literature.
I don't expect you to quite explain the FDA's view on that, but what is even the theoretical risk for how you might be accelerating rates of low-grade transformation to high grade or whatever else they might be worried about?
Yeah, I think one potential risk here or one risk they may have contemplated was misattribution of initial histology. So if for some reason, a patient was thought to be low grade but was, in fact, high grade, then we might have missed the opportunity to more definitively treat that patient. Turns out our clinical experience suggests that that's not, in fact, a concern, but we needed to prove that, and I think we have.
Yeah, and I, you know, I think the other thing is they say: "Well, you know, you have to wait three months." So are you harming those patients in those three months? So by not treating them with the standard of care for those three months, are you hurting them, and are they more likely to progress because you waited the three months, right? To see if it didn't work, if UGN-102 didn't work, have you harmed those patients? Which clearly isn't the case from our data, so we feel really good about, you know, about our ability to address those questions and concerns that they raised.
I assume this is gonna be a bit of an unusual ODAC with some guest urologists on board? Or, what do you think is going to be their plan?
Mm-hmm.
To address a question that's very much a urology question with a cancer panel?
I'll just say that personally, I'm hopeful that there are some urologists, and it's not that I don't like meeting with the medical oncologist, but it will be nice to have some people who actually do this work in the room. I would imagine you're right. There probably will be some urology folks at the meeting.
Yeah, I guess I would sort of argue is the good news and the bad news, right, with the oncology division. So because they are used to new treatments, they tend to have a very good view of a benefit-risk profile. So they're usually err on wanting patients to have treatments because these cancers are not curable, so that's sort of the good side of it. The bad side of it is there really is a misunderstanding of this disease, right? That low grade doesn't progress to high grade. It's not. It doesn't work typically like a traditional cancer, and that's been hard for them to get their arms around, to your point, because they're medical oncologists and not urologists, who clearly understand this disease.
Let's say we fast-forward to a time when you've got the opportunity to bring UGN-102 to the market. First, we've just referred to it as a big market, but maybe you can put some.
Yeah.
Parameters around.
Sure.
How big we're talking?
No, absolutely, and we talked earlier about the 6,000 patients for JELMYTO. This is 80,000 patients, so that puts it in perspective. It's 10 times the size. Still relatively small, if you think about it, but for cancer and oncology, you know, 80,000 patients. The other important thing is every urologist treats these patients. So when I talked earlier about 6,000 patients, you might see one or two. Every urologist will see multiple of these every year, so it's a, you know, disease that they see, a disease that they treat. The total market from a dollar perspective is over $5 billion. So if you had all of those patients, and they were treated with treatments, you know, averaging at about $100,000 per patient, you know, you would get over a $5 billion market.
We have said publicly that we expect UGN-102 to be over a $1 billion market, or in and of itself. You know, that gets you, you know, less than a 20% penetration rate, you know, into this market. So that kind of gives you some perspective of the market size and where we expect we'll be.
Where, where do you think the early adopters are gonna be in this paradigm? Are they gonna be post-TURBT? Are they gonna be with TURBT? Are they gonna be?
Well.
Before TURBT?
I'll tell you what physicians have told us so far, but you're right in the sense it's the right question. Our studies were done as primary treatment, so without TURBT. But some physicians have said to us, "Look, I'm gonna do a TURBT anyway, then I'll come back and give this." We won't be promoting that way because that's not, that's not our label. It won't be what we studied, but obviously, physicians may choose to use it that way. What they've said to us are a couple things: One, that the early sort of low-hanging fruit are those patients, you know, Mark talked earlier, 23% have five or more TURBTs.
At our event in June, you know, one of our physician panels said, "I just saw a patient who had 20 TURBTs." So clearly, the earliest adopters will be in those patients who've had multiple recurrences. Those that they call early recurrences, and early recurrences, they recurred in less than a year. And then lastly, you do have a group of patients who most feel like should not be going through general anesthesia. And so those are kind of the low-hanging fruit, but frankly, after we got the data in June, with the 80% durability, you're hearing more physicians saying, "Well, I'm gonna need to offer this to all my patients." So it's been very different, and then others have said, you know, that especially the JELMYTO users and those that have had experience will definitely be the early adopters.
So we, you know, we hear varying things. We don't hear from anybody that they're not going to use it. We do hear from people, "Well, I'm a surgeon, you know, and I get it 100% or 100% of the time," right? So you do hear that part, and for them, they don't wanna walk away from surgery, so those are more the naysayers. But for the most part, you hear physicians say they all have patients that they'll want to use UGN-102 in.
How do you address the market with a commercial sales force? Where are you already, and where do you need to build?
Yeah, it's a great question because we've changed in the last week. So, we have 42 reps today, and we had been communicating. We thought we would go to 60. Now, we feel like, given the data, given the analysis, the physicians, the high touch that we need, we are likely to go to 80. So we wanna make sure that we resource this launch in the best way possible, and so in addition to our representatives, our main representatives, we have clinical nurse educators, we have account managers, we have, what we call operations manager. I talked earlier about the logistics being really important, and we have field reimbursement managers because that's the other thing, right? Reimbursement, these are buy and bill drugs. They're expensive drugs. Physician offices wanna make sure they don't lose money and that they properly get reimbursed.
We will have that support system in place for doctors' offices.
Okay, so you're going all in on this one?
All in.
Okay. Talk about all in, and, let's talk about the stock. I mean, I'm a stock guy. Stock hasn't reflected $1 billion.
Right.
Or more in sales for 102.
Right.
What are investors missing about your company?
Yeah, I think it's a great question, and I'll give you my sort of two cents and would love, Eric, for you to give us yours. But it. We've been very underappreciated for the last, you know, five years. I think the questions we hear are, "Is the FDA really going to give you an approval on a single-arm study? They've said they're gonna give you an ODAC. Why are you getting an ODAC if the data's so compelling?" So they're wondering what they're missing, to your point. You know, wondering what they're missing. We have seen a very high increase in the short sellers recently in the last, since the June event. You know, much higher than what we had seen. So it's all the way up to 15%+ .
So that's, you know, obviously, there. That has hurt us, and we have seen a couple of our long institutional holders whose funds have kind of, you know, come to an end, you know, get out of the stock. So we think that's been a lot of the pressure on the stock. Obviously, September from a macro environment wasn't great, but look, we feel very confident in our launch. So I think October, when you hear about the acceptance, I think IP, we just announced yesterday, some extension in our IP, and I think, you know, understanding the transition into, from the old formulation to the new formulation, all of those are sort of bringing some pressure on the stock. But again, hang in there. Great time to buy, you know?
We, you know, feel, I say, very confident in it.
Okay, I'm looking forward to that FDA decision as a key de-risking event.
Sure, I think so.
Great.
I think so as well.
We're out of time. Liz, Mark, thank you so much for being here today.
Thank you.
Thank you very much.
Really appreciate it.
Yeah, thanks.
Good to see you.