Welcome to this fireside chat with UroGen Pharma. I'm very pleased to welcome Liz Barrett, President and CEO, as well as Mark Schoenberg, Chief Medical Officer. Welcome. Thanks for joining us.
Thank you. Thanks for having us.
UroGen has developed a really interesting RTGel technology. Maybe for those that are less familiar with it, could you just remind us of what makes this technology so interesting and how have you applied it to your products?
Yeah, I'll ask Mark if he doesn't mind to take that.
Sure. Thanks for the question. This is an ingenious combination of polymers that do something that's counterintuitive. When they're mixed together at a cool temperature, they form a liquid. As that liquid warms to body temperature, it forms a soft gel, which is ideal for delivering drugs to various warm, wet parts of the body. We're a urology company, so we are very interested in a warm, wet part of the body called the bladder and the upper urinary tract.
We're able to use this technology to deliver medicines to parts of the body that normally are bathed in urine and would readily wash out aqueous medications. This is a way of delivering medicines for an extended period of time to a part of the body that's hard to get to and hard to treat.
Great. Obviously you do have Jelmyto on the market for some time now and more recently approved Zusduri for bladder cancer. Maybe if you just step back for one second and remind us of the opportunity for intermediate-risk NMIBC, with the therapy approved, and what kind of unmet medical need the product addresses there?
Absolutely. There are about 60,000 patients with what we call recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. There are about 20,000 newly diagnosed patients with intermediate risk every year. Our patient population is the 60,000 patient population. One of the defining factors of an intermediate-risk patient is that they recur. What happens is 23% of these patients will recur five or more times. 68% will recur two or more times.
Over their lifetime, unfortunately, they have to go back for repetitive surgery. Mark likes to talk about it as being a surgical failure because clearly the surgery did not work or did not work for a long enough period of time. That is really the unmet need, finding something that will allow these patients to have more recurrence-free survival. I'll ask Mark just to talk about maybe the difference between low-grade and high-grade and why it's important to delineate the two and why we are in our situation where these patients go through repetitive surgery, m aybe just talk a little bit about the differences.
Sure. As anybody who's been following the space knows, there is an entity in bladder cancer as a spectrum of diseases. There is an entity called high-grade non- invasive bladder cancer that has historically been treated by surgical resection of visible disease followed by treatment with a drug called BCG. When patients recur after that treatment, often historically they had to have their bladders removed. There has been a lot of activity and many drugs have been developed recently and some even approved for treating that relatively small segment of an adversely affected population.
We're working in a slightly different group of patients, namely exactly who Liz talked about. These are very commonly encountered in urologic practice. Patients who have what's called low-grade disease. This is a chronically relapsing disease that doesn't typically progress to a life-threatening form of illness, but is very difficult to manage, highly recurrent, a real burden both to the system and to patients. We're working in a different space dealing with a different problem. Really, it's recurrence control and providing patients with an intervention-free interval of life that is greater than what is currently available.
Maybe just one more question. Do low-grade intermediate risk patients eventually progress to high-risk patients or is it its own?
Yeah, it's a great question. People have been worried that that in fact was the case. There are large studies now, including some that we have published about our study populations, showing that the progression rate to high-grade disease is exceedingly low, low single digits. That actually can give doctors and patients confidence that treating with a paradigm-like shifting technology like ours, one that does not rely on surgery, is actually safe and reasonable and does not require surgical intervention prior to the administration of the drug.
Great. Obviously Zusduri was approved here this June, earlier this year. Yeah. Maybe just talk about in general how you're leveraging your existing infrastructure around Jelmyto perhaps to drive the launch.
Sure. When we launched Jelmyto and up until about a year ago, we had about 40 reps. In addition to representatives, your typical, we have our key account directors that call in the C-suite, but we also have clinical nurse educators because you always have to keep in mind that this is not a typical drug or a typical pill or infusion. It is actually a procedure. We have clinical nurse educators that help to train and actually participate in some of the instillations to ensure physicians are familiar with how to do it, but mostly nurses are familiar with how to do it.
That is the group that we had prior with Jelmyto. When we launched Zusduri, we doubled the sales force. We have about 82 reps, again, more clinical nurse educators. Biggest barrier to adoption is reimbursement. We also have field reimbursement teams and key account director teams that work and help with reimbursements as well as our medical team. We have about 130 what we call customer-facing roles.
The good news is there is almost 100% overlap with Jelmyto users. There is more potential Zusduri users, which is why we expanded. While we used to call on about 5,500 docs, we now call on about 8,500 docs with our 82-person sales organization. The good news is we have a highly leverageable organization and infrastructure, not only in the field team, but also in the other parts of the business as well.
Right. Obviously, again, the product's in the market now for about four and a half months. Just remind us what we can share about some of the early launch metrics that you've been tracking, precision outreach, patient side active patient requests, prescribe.
Yeah, absolutely. We just shared our Q3 earnings last week, and we did something that you don't usually do, but we felt like it was really important to do in that we also shared October revenue. We did that because what, again, as I mentioned before, this is a procedure. It takes a lot of time and energy for the operational logistical aspects of getting the drug. When you have what we call a patient enrollment form, that means a patient has actually been identified by the physician as wanting to treat with this drug.
It can take up to 60 days before a patient actually gets dosed. Because of that, and I think a lot of people are familiar with our regulatory path, we had an ODAC that was "a split vote," but five to four against. We did not hire the incremental sales team until after we got approval. We actually did not really launch until the July-August timeframe. If you take that and think about even the early adoption, if you are taking up to 60 days and you really do not start to see those patients, and we recognize revenue basically when a patient gets dosed because we do not really have inventory.
Sometimes a hospital may bulk order, but for the most part, it is a dose that goes into a patient, and that is when we recognize the revenue. Because of that, we wanted to really share the fact that we had about $1.8 million in revenue in Q3, but we had $4.5 million of revenue in October alone. Obviously, over double the amount. That is because we are finally starting to see the funnel, what I call the funnel.
The top of the funnel has been very strong from day one, but finally starting to see those patients get dosed. We have both a conversion rate and a time to conversion that we are working to make sure we minimize the disruptions during that timeframe and can get that to a better rate. As we get into, and I think the market recognizes that $4.5 million in one month puts us on a great trajectory.
The other thing that I shared was that our patient enrollment forms, which is our early indicator of demand, is at the same pace today for Jelmyto after four months on the market that it is for Jelmyto after five years on the market. That also gives you a reference point for the number of patients, right? When we talk about Jelmyto's 6,000 patients, Zusduri's 60,000 patients, and you can already see that being the case.
Great. We have received very favorable feedback from physicians that we talked about Zusduri really being the first systemic or the first actually locally administered, but medical treatment for low-grade intermediate-risk bladder cancer as opposed to surgery. What have you seen so far in terms of how the drug is being used in the market? Is it used perhaps where in the relapse history, for example? Is it used early or later? What types of patients are the early adopters?
Yeah, as we expected, the patients that are getting treated initially are your patients that have had multiple recurrences. Our research before we launched said that the three low-hanging fruit of where they would use it in the beginning is early recurs. Those patients that are recurring at three, six, nine months, those multiple recurrences, and then there's a small group of patients that aren't really what they would consider to be good candidates for surgery. I think where we're seeing them initially is in those heavily pretreated patients as well as potentially a patient that they really don't want to put under. That's where we expected.
Okay. Obviously demand is there. Some folks are now wondering, as you now have the permanent J code in place starting in January 2026, what type of inflection point could that provide for Zusduri?
Yeah, what we've shared, there's sort of two, I think we think good analogs. One is Jelmyto. So our own Jelmyto, as we saw the pre, post, pre-imposed J code. The other one is ImmunityBio's Anktiva. They came out in their second quarter earnings, and they had about a 220% increase in revenue in the six months with the J code for the six months prior to the J code. Their timing was very similar to ours. Obviously, they also are in urology and non-muscle invasive bladder cancer, although a different patient population. We think that that's a good analog.
Okay. Yeah, any physician feedback in terms of the reimbursement process today and to what degree that could change with the J code?
Absolutely will change. We have had a number of physicians, and Mark can attest to this as well. We are rarely having a clinical discussion with doctors. Rarely are they questioning or challenging the clinical conversation. It is all about reimbursement. It is all about logistics, the operational hurdles, and reimbursement. When I am out talking to doctors, Mark is out talking to doctors, that is what they tell us. As soon as I get the J code, they just have more confidence in the J code.
The other thing is some payers may have restrictions before the J code where they will reimburse at a lower rate. Unfortunately, we cannot do anything to help that situation. When the J code comes, again, we have had a lot of physicians that said as soon as the J code comes. What will happen in the new year, January 1, everybody's insurance resets. We will have to go through benefit verification for all of our patients, anybody who's in our funnel, anybody who's currently on drug. We do expect to see a step up in acceleration post the J code.
Right.
What are you seeing so far? I know it's really early, so I'm not sure if you can, but in terms of treatment duration or numbers of doses that patients are receiving in practice compared to the trial experience?
Yeah, we are seeing the majority of patients getting six doses. We have sort of guided to this average of five and a half to 5.8 in the long run because you will have some patients that won't get all six doses. Right now, initially, we are seeing most of them getting six doses.
Okay, great. Is there anything else that is left to do in terms of post-market commitments to the FDA around Zusduri?
You want to talk about post-market?
Yeah. Our pivotal trial, the ENVISION trial, is actually a five-year study. That was the commitment, to continue to follow those patients long-term to provide both safety, and obviously we'll be interested in the efficacy and durability data as well, but safety particularly.
Okay. A very big question is obviously when we think about this 60,000 patient opportunity, what is a reasonable assumption for peak market penetration into the space?
You know, what we've said publicly is this will be a billion dollar. We expect it to be a billion dollar plus. That gets you, if you have a 20% penetration, you're at $1.2 billion roughly, right? The math. I think we're very comfortable with that. I think the early indication when we're talking to physicians about, and the research that you guys have done with physicians, some of our other investors have done research with physicians, there's a lot of enthusiasm and energy to utilize this in their practice.
We expect that that's a fairly conservative position to be in. Time to peak a little bit longer than what you would typically see in oncology. I was laughing with a friend of mine last night. We were, sorry, Mark, talking about urologists being much slower than oncologists are. That typically happens. So you're probably a four- to five-year to peak versus oncology is typically three years.
Right. Will you give guidance, revenue guidance next year?
I don't think so. Not in the beginning of the year. I think maybe after a couple of quarters with the J code, but we're going to want to see how that works before we provide any guidance.
Right. What have you said around gross-to-net adjustment for the?
Yeah. Right now, Jelmyto is about 75%, and we have guided that that's a good number for Zusduri as well. Personally, I think that's very conservative. It will be a little bit better than that because two things. In the beginning, you see a lot of the usage both in Zusduri and Jelmyto in the hospital. 340B has been a huge drain on our gross-to-net. The increase in the 340B discounts has been a big driver of our reduced gross-to-net for Jelmyto.
I think in the beginning of Zusduri, also you'll see more in the hospital, but that will move to the community setting. I think hopefully when that moves to the community setting, you won't see as stark of a discount on 340B. Hopefully it will be a little bit better than that, but that gives you a good range.
Okay. As we think about this low-grade intermediate risk market longer term, there are a few other products that are being evaluated in this space. How do you feel about your position as first mover in the category when you think about future products perhaps entering?
Absolutely. I'll ask Mark to comment on both J&J and CG, kind of where they are, where they fit, and then I'll add any commentary.
Sure. Thanks. These are drugs that have been developed to treat BCG unresponsive high-grade disease. They're, as you point out, going to move into the intermediate risk space. It's important to remember that they are both adjuvant therapies, and that means that they follow surgery, in contrast to Zusduri, which is a primary therapy that does not require surgery. That might actually be, for starters, the first important differentiator. Secondarily, these products, CG's product, J&J's product, require a very lengthy on-treatment time period for patients. In the case of J&J's product for high-grade disease, there's a several-year commitment to exposure to the drug.
We'll see about CG, but they probably will have a maintenance phase as well, in contrast to six doses and you're finished with therapy for Zusduri. There are some workflow issues in the urology office that will be impacted by those different durations of care. There are some other issues related to local irritation with the J&J product that may be a problem for patients long-term, and some mechanistic issues that may or may not be important with respect to the CG product in the context of low-grade disease.
There are a number of unknowns that are important to consider when thinking about those medicines as being competition to Zusduri, which, as you point out, will be in the market for a couple of years before they are relevant.
Right.
Yeah. I think that's important, right? Not only will we be first to market, but I think it will be, I would be surprised if anyone has clinical data that's actually better than ours. To Mark's point, it's in addition to surgery. The data that you're seeing there is in addition to surgery. Ours is alone. The idea that a patient can have six doses and then not have treatment, if you talk to patients, that's huge. The ability to have this not only recurrence-free, but also treatment-free life for them, I think will make a big difference.
Frankly, what I see mostly when more drugs come into cancer treatment is it expands the market. I mean, we just said ourselves, we've got a $5 billion market, $5 plus billion dollars, really, it's more than $5 billion market, and we're 20% of that. There's a lot of room for others. I'm happy for patients to have more. I've been in oncology for 30 years. Patients need more treatments. We're hopefully going to head toward more cures in the future, but until we get to that point, these patients will see multiple therapies in their lifetime.
Right. Then I had a question on your UTOPIA study, which you recently announced to succeed on your positive outcomes in the three months readout. Maybe just remind us of the 103 product and how it's different from Zusduri and what are your plans with it?
Yeah, you, Mark, you want to talk about that?
Sure. 103 utilizes a proprietary mitomycin that was developed by a German company called medac. Actually, the reason we went looking for this was for a secondary supplier. It was not our original intention to come up with a whole new product, but as it turns out, medac's mitomycin is very rapidly made from an industrial perspective compared to what we're currently doing, manufacturing our mitomycin for Jelmyto. It shrinks the production cycle.
It also uses excipients that make it easier to solubilize. That will have some beneficial effects that are realized in the pharmacy during mixing of this product. The product is the same. The medicine is the same. As the results from UTOPIA that were just released emphasize, the clinical impact is the same, but there are some both production and use impacts of the new formulation that are very favorable.
Great. Just going back to the Zusduri approval process, there was some drama around that, as you know. Any visibility on regulatory clarity on filing based in the UTOPIA study?
Yes. This is a new formulation of an existing product that has a predicate, which is Zusduri. In terms of 103, we have interacted with the FDA and feel certain that we can move forward with our NDA as planned and announced.
Okay.
I'll say that we triple-checked that, right? Just to make sure. Whenever I think about drug regulatory people crazy, I say, "Just send them one more email. Just one more confirmation." We can't have any room for error. That is the case. There's no ODAC. They also are allowing us to file and update with the 12 months during the filing. That will allow us to file a little earlier and be able to, so all of the things that we were looking for clarification in our pre-NDA meeting, we were able to get.
Remind me, what did you say around timing for filing and perhaps?
Yeah, we just said second half of 2026 filing, approval in 2027.
Okay, super. I know you have a few other pipeline product candidates as well. Just remind us of some of the activities that are ongoing there.
Following on the heels of our conversation about 103, there is a product called 104, which is the successor product for Jelmyto. It will follow, it is utilizing medac's proprietary mitomycin. It is a very similar idea for the upper tract. That will follow about a year later than the 103 program, the same pathway. Another NDA and then submission and approval probably a year later, so 2028. There is that.
104, we also have a very exciting oncolytic virus that we purchased this year, and it is called 501. This is a specially engineered virus that not only kills cancer cells directly, but incites a very specific type of anti-tumor immune response. The proliferation of the virus is very favorable and very rapid. That is currently in IND enabling studies. We will go into phase one in 2026. We're very excited about this, not only because of its applicability to bladder cancer, which is where we're going to study it first, but also because it could potentially be used in other cancers, and we will explore that subsequently.
The only other thing I'll add is that for Zusduri, for UGM-103, once we get that approved, but even before that, we are going to move 103 into high-grade disease and potentially other patient populations. We'd love to really have UGM-103 studied across all of the different patient populations. There's a lot of them, right? It's segmented, unfortunately, or fortunately, depending on how you look at it, but we would look at doing something maybe in newly diagnosed adjuvant for low-grade IR. We would look at doing high-grade post-BCG. Maybe you do something in combination. We are looking at an array of life cycle management opportunities for UGM-103. I keep saying Zusduri, but it's actually the follow-on 103.
Right.
Maybe just one more question on the commercial side. Have you noticed any commercial synergies around Jelmyto, just given that you have this increased commercial effort around Zusduri now?
Absolutely. Actually, I think last week I got an email that one customer, where we know two patients were treated with Jelmyto because they were in talking about Zusduri. We expected that. We thought that would happen. Yes, to your point, we're calling on more doctors. Once they adopt Zusduri, it's harder to do Jelmyto. Once they adopt Zusduri and it's easier in their practice and they're doing it, they're more apt to use Jelmyto.
Physicians, we've already seen some of our revenue come from those doctors who have prescribed Jelmyto, who had never prescribed Jelmyto before, and did so as we were talking about Zusduri. We absolutely expect that growth to continue on Jelmyto.
Great. Awesome. Thank you, Liz and Mark. Really appreciate the time today.
Of course. Thank you.
Thank you.
Take care.