All right. Good afternoon, everyone. Thanks for joining us. I'm Tara Bancroft, one of the senior analysts here at TD Cowen. Thank you for coming and joining us at TD Cowen's 45th Annual Health Care Conference. For this next session, we have UroGen here, and we're doing a fireside chat.
Liz and Mark, it's really great to have you. Thank you for joining us. It's our pleasure to host you. Before I get started, I do want to say to the audience, please feel free to chime in with any questions that you have. I'm happy to take them. Raise your hand or give a shout, whatever you want. I guess to get started, Liz, can you give us a general overview and update of where you're at today?
Oh, that's a loaded question. Where are we today? Just to take a step back, you know, I joined the company about six years ago. We have this unique technology called RTGel. It's reverse thermal gel technology that allows medicines to dwell longer in the cavity. We launched our first product, which was really for a rare disease called upper tract urothelial carcinoma. That's been on the market. We launched right into COVID. Now where we are as a company is really this will be, I would say, the most transformational year for our company. This is what we've been waiting for. When I joined the company and we had Jelmyto for the upper tract, it was always, okay, that's a small opportunity, but the opportunity is really in bladder cancer. We're going after a very unique space.
I know I'm echoing, but going after a very unique space called low-grade intermediate-risk non-muscle invasive bladder cancer. The bladder cancer space has been very busy recently. When I joined, it wasn't. There were very few companies that were in the space. The standard of care is really transurethral resection of the bladder tumor, repetitive surgeries, which Mark knows a lot of because he does a lot of those. We were really trying to change the paradigm. Now we're finally in a situation where the FDA is reviewing our application. We have a PDUFA date of June 13 of this year. We're going from a company with one small product for rare disease to an opportunity where we have multiple products in the same space, luckily in the same call universe.
We have been able to leverage the company, but really move it to a company in which we have an opportunity to build a long-term sustainable growth business. This indication, this product will help us and be the foundation for us to actually be able to grow this company into a long-term sustainable growth company. We are very excited. Like I said, the most pivotal time, I think, in our company.
Yeah, agreed. Okay, so June 13 PDUFA, you filed based on the phase III ENVISION data. Can you give us the key highlights of that data and what you think will be the most strong in supporting a potential approval?
Yeah.
Sure, thanks. Just to remind those of you who have not been following our story closely, UGN-102, which is the product for which the NDA was filed, is mitomycin in our reverse thermal gel platform. It is given as a primary therapy for the treatment of intermediate-risk non-muscle invasive bladder cancer. That is in contrast to the standard of care today, which is surgery. That is usually done under anesthesia by a surgeon with a scope, and it is a removal of the visible tumor. That is the standard of care. This instead is an office-based procedure that can actually be done by a nurse. It is given once a week for six weeks.
The ENVISION trial, which is the pivotal trial and basis for the NDA, was a study in 240 patients of how that six-weekly treatment produced a complete response rate and then a durable response in patients with intermediate-risk disease. The numbers to keep in mind are that in the study, the complete response rate was 80%. At three months, about six weeks after the last dose of medication, 80% of patients did not have tumor after treatment. Following those patients out by Kaplan-Meier analysis, 12 months after that three-month initial evaluation, more than 80% of those patients were still free of disease. It is hard for me to tell you how remarkable those things are in urology if you are not a urologist. Those are remarkable numbers. We do not see them with any of the typical therapies we offer these people.
Remember, this is an office-based procedure. This is not an operation, which is what these people are typically used to. Really outstanding numbers and, very importantly, incredible durability of that response as well. Those, I think, are the things to keep in mind. Finally, as just a sort of coda to this experience, we asked patients as part of patient-centered outcomes research done independently by the University of North Carolina how they felt about this therapy compared to surgery, which all of them had had in their past treatment experience. The vast majority of patients preferred the UGN-102 therapy to surgery, not surprisingly. A well-accepted, very well-tolerated, safe, and apparently highly effective therapy for this disease.
Great. Thanks for that overview. You guys submitted the or you finished submitting the rolling submission back in September. Have you had the mid-cycle review yet? I mean, I guess any kind of color you can give us on any interactions that you've had with regulators. Then we'll get into maybe the potential for an ODAC.
Sure. There will not be an ODAC, so there is not a potential for one. We have not had our mid-cycle review meeting, but it is upcoming. We will have that shortly. The interactions with the FDA, and then I will turn it over to Mark to sort of talk about how we have been planning and preparing. They have really. I mean, the good news is they have had audits of clinical sites. We have had inspection at the office. It is your typical IRs that have been coming in, your information request. The good news on the CMC part of it that everybody gets worried about is it is the same CMC that we have for Jelmyto. We actually do not get a lot of questions around CMC. Initially, the FDA was really focused on progression and safety.
We do not really get any questions around that either anymore, I think, because they have recognized, given the data that we have shared. Today, it is really about efficacy and do you have substantial evidence to demonstrate that. Maybe Mark can just talk a little bit about the feedback we have gotten from the FDA, all along very consistent feedback about what they are going to be looking for and what they are going to be asking at the ODAC.
Yeah, one thing that is nice, I guess, about this program is it's been going on for a while. We have gotten to know the FDA and their sensitivities and concerns about this particular approach to treating bladder cancer. Remember, what we are providing now is an opportunity to treat people primarily with a drug-based therapy rather than surgery. That is a bit of a paradigm shift in the context of this particular patient population. We know, as Liz pointed out, that they will be very focused on the benefit-risk analysis of the data from the ENVISION trial, the pivotal trial. Do we satisfy that requirement that there is, in fact, an overwhelming benefit compared to the risk? We certainly believe that the data support that.
In addition, because we ran another phase III trial, which some of you may be familiar with, and the results of these were published in the Journal of Urology last year called the ATLAS trial, we also have randomized data against the standard of care, which is, again, transurethral resection. We do have a wealth of information about how this drug compares to the standard of care. The agency will be interested to know how do those data support our contentions about the value of UGN-102 in the context of the ENVISION data. Finally, how clearly do we articulate the unmet medical need, which we think is quite clear in this population. It is a matter of providing a better opportunity for recurrence-free life in this patient population. Our data support that as well. We think those will be the focuses of conversation.
In the submission package, you had the ATLAS data in there. One question that I have received from several investors is, because of the inclusion in that data, and I know the study did not go to completion, which you're free to talk about if you'd like, is there any potential that they could see the benefit in newly diagnosed patients, like less recurrent patients, and that that could potentially be included in a label?
When we put in our submission, we did put in the broad label to treat patients with low-grade intermediate-risk non-muscle invasive bladder cancer. Because, like you say, ATLAS and OPTIMA II , had both newly diagnosed and recurrent. It's important to note that almost all patients, when they're newly diagnosed, will get a TURBT for diagnostic purposes so that they can grade to make sure that it's a low-grade tumor. We always knew that over 90% of our revenue would come from the recurrent patient. If you talk to doctors and patients, Mark talked about the fact that it's an elderly patient, have comorbidities, they're taking other meds. There are a handful of patients that just should not go under general anesthesia, should not go to surgery. You want to have that available for patients.
It is not anything from a financial standpoint as a company, but it is if you want to do the right thing for patients, if you want to give physicians the option, you want to have it available. That is what we are asking for. Is there an opportunity that the FDA will come back and say, well, the pivotal study was just recurrent, so you will only get recurrent? Sure. We are okay with that. Again, it does not impact us financially, but it is more of a, do you want to make it easy for physicians to use it rather than having to jump through hoops if it is considered to be off-label? We will be asking for the broad label, and we will have to see what the FDA says about that. I am sure that is going to be one of the questions at the ODAC, right?
If we get approval, if they say, we'll get it for the broad label or for a more limited label. It doesn't impact our company, but to me, it's more of a pride thing. You want doctors. You want to make it easy for doctors to be able to use it.
Yeah, that makes sense. I guess ahead of the ODAC, which, have you set a timeline?
All we know is May. There's not a published date yet. They said they'll give us, I think, a day notice before it goes public.
Really?
Before it goes public, right? As soon as they do that, we'll make sure everybody's aware.
Okay, yeah. All right, so about roughly a month or maybe even less from the PDUFA date. One of the things that people will be paying very close attention to will be the briefing docs and the outline. Those are usually some kind of debate questions of what people are going to be focusing on. I'm just curious how you guys are approaching without knowing that information that's going to be in those documents or what the discussion is actually going to entail. What kinds of things are you preparing for ahead of time or really that you'd like investors to start setting expectations to hear about?
As you can imagine, since the agency, as Liz pointed out, has been signaling to us for a long time that we would likely go to an ODAC, we started preparing a while ago. We have been very busy doing what are called mock advisory meetings with experts, particularly medical oncologists and urologists, but also, importantly, statisticians who have given us the opportunity to not only present our case, but also who have been candid both in role and then subsequently telling us where the deficiencies are, what explanations we are providing are not clear. We have had a number of those. We have a number more planned before our May meeting with the agency.
We are very busy preparing for exactly the types of questions we've been talking about this afternoon, namely the risk-benefit analysis of the ENVISION data, the very specific statistical questions around how to understand how ATLAS, though terminated earlier than originally planned, does significantly contribute to our understanding of the complete response rate provided by UGN-102 compared to surgery. How do the durability of response rates in those two different arms really bolster our argument, strengthened by the ENVISION data with respect to how UGN-102 performs in this population? Those are the types of things we've been working on. We have had some very specific learnings, particularly because we know that the agency will have on the committee a number of medical oncologists who are not experts in urology and who may have very little familiarity with the disease space.
We are concentrating heavily on creating a presentation that is both educational and fulsome in terms of its description of UGN-102's benefits.
The other thing we've done is we are inviting as many, the more negative you are, we want you there to do exactly what you're talking about because we want to be challenged. We want to make sure we don't miss anything. Is there anything that we're missing so that all of that we prepare ourselves to answer any question or any challenge that may come up in the ODAC. I mean, the FDA doesn't go to an ODAC and send out something that says, oh, isn't this wonderful, right? They're going to challenge you. We will be prepared for all of that. We want to make sure that we're not caught off guard. The team has been working extremely hard in making sure that we're covering all of our bases.
Yeah, I mean, good for you for doing that. I know we don't know the voting question yet. This is one of those impossible questions to ask that I'm going to ask anyways. If you had to peg a percent likelihood that you believe the ODAC would have a positive outcome for you, what percentage would you say that is?
We would say that it's over 90%.
Great. Okay. I guess we can turn to I know the team is probably very busy with ODAC preparations, but also launch preparations. Where do you stand on that? What has been done? What still has yet to be done?
Yes. We actually have our Chief Commercial Officer here with us today. David joined us June of last year. That has really been his main focus. It really is on gaining insights to physicians, how are they thinking about a lot of what we would hear from investors or other people is, well, surgeons want to do surgery. Actually, that is not as true as everybody thinks it is. They want alternatives, but they also recognize that if they can do this procedure in their office, it is very beneficial to the practice. It is very beneficial to the patient that that is a good thing. We have been working on messaging. Mark talked earlier about durability. The duration of response and being able to have longer recurrence-free and longer intervals between treatments is very compelling, both for physicians and for patients.
We will take our commercial force, sales force. We had 42 last year when it was just Jelmyto to 83. We will almost double that organization. We have field reimbursement managers. We have nurse educators. We also have operations managers. We really have a full group, comprehensive group of people to impact because what we have to do is make it as easy as possible for a doctor. We have to make it easy. It has to fit seamlessly into their practice. That is really what we are focused on. When you compare it to Jelmyto, Jelmyto, because you are manipulating the upper tract, you have to have special equipment. It can only be done by a physician. Or you use a nephrostomy tube, which still has the tube that has to be placed in the body. Versus this, you walk in, a nurse can give it.
It's done in the office with a catheter. It is a much simpler procedure, but you still have to have the operational pieces put together. We are doing everything we can to ensure that is very simple and very easy for the doctor. We mix the product because you have to take the gel and the product. We offer, we will mix it for you and send it to you ready to go. Anything we can do to make their life easier. Importantly, in the beginning, particularly making sure that we are targeting appropriately. We are excited about building the group and excited about the messaging and the feedback we are getting from physicians. They are very excited about it.
One of the things when we talk to some of our investors, we have investors that sometimes come to us because they were out talking about another product in bladder cancer, and the doctor is bringing up UGN-102. That is actually a good way for us, for people to hear about us and who we are.
Now that it sounds like awareness is growing, gaining a lot of momentum with demand and interest, have your thoughts changed at all since I know you hosted that KOL call with the data, and you had those five KOLs that talked about which buckets of patients would be treated. I'm just curious how that has evolved over time, if at all, and where do you stand now on the types of patients that would be treated like right away versus a year later? Like which ones are more difficult versus easy to treat?
Yeah, I think you still have your low hanging fruit, right? You still have those patients who have had multiple recurrences. You still have those patients who have early recurred, recurred very quickly. I think that's still, and I think actually Dr. Linehan at the meeting, she said it. She said, I used to think about who was I going to use UGN-102 in? What patient population? Now I think about who am I not going to use. It's really a smaller group of patients that she would not use it in. That's the type of things we're hearing, right? It's been good because I think physicians, and particularly after they get reimbursed, reimbursement's always a big thing. These are buy-and-bill drugs. They're more comfortable with that. I think that I think it opens it up for their patient population.
Which patients would they not use it in? Small percentage, but who are they?
Yeah. Who would you not use it in?
I think we anticipate a label that is going to specify low-grade disease. I think it would be unwise for physicians to use this in patients with high-grade disease, absent data to support that. That is number one. I think there are patients who have tiny tumors that can be successfully ablated in the office without any other intervention. People with what is really called bona fide low-risk disease, those are patients who probably do not need this. As Liz points out, there is a whole swath of patients, as apropos what Dr. Linehan was alluding to originally, who would benefit from this. We have traditionally operated on somewhat unthinkingly. There is a large group of people who will benefit from this. I think it remains to be seen how the community uses it.
Yeah. Community versus academic, it got me thinking. The types of centers that you'll be targeting, who do you think will be the earliest adopters versus later? What's the difference between them? How are you going to target them?
Yeah. Ultimately, most of the revenue and most of the patients will be in the community. In the beginning, it's a great question because in the beginning, it's going to be in the institutions for a lot of reasons. One, we know that they adopt new therapies quicker. Two, we also know that they don't worry about reimbursement because they're not worried that it's coming out of their pocket and their community practice, but the hospital takes the burden of that. In the beginning, we expect that it will be in the institutions. Jelmyto was like that, but for other reasons as well. 80%, now it's about 50/50. I think it probably won't be that dramatic in the beginning, but ultimately, you'll see the majority of it in the community practice. In the beginning, it definitely will be institutions.
We already know our big users of Jelmyto, your academic centers that use that, very comfortable, they also are the ones who are ready to use UGN-102 as soon as it gets approved.
Yeah. Based on the work that you're doing, you said for the ODAC preparations, you want to choose the ones even that are super, super negative that never want to give up their surgery. Do you know, I mean, I know that there's always a chance that they still could adopt it over time. Do you know what, if you had to ascribe a percent to it, that would potentially be like never adopters that just love surgery?
Oh, I don't think it's because they love surgery so much. I think there's probably about 20%. It really is sort of your 80/20 rule. They're more like, no offense, Mark, I'm such a great surgeon. I get it 100% of the time. Never a problem for me. It's those. I'm always apologizing.
None taken.
I'm always because I'm sure Mark thinks he gets it 100% of the time.
Of course.
Because Mark still practices. He still does these operations. I think about 20% of the physicians have that. Again, more likely, though, it's kind of interesting because some of them, we talk to them today, and even they'll come to some of our ad boards, will be very negative in the beginning, right? By the end, they're talking about what patients are going to use.
Yeah. No, I think that's really interesting. Let's see. Otherwise, for commercial stuff, have you spoken yet about what your pricing assumptions are going to be?
Yeah. We have publicly talked about $18,000-$19,000 per dose. That was actually data from research that we did before we saw the durability. We are relooking at pricing right now. You can see that that's significantly less than what the others have had in high grade. We do think that low grade, we're going to price for the value, right? Think about from a low-grade perspective versus high grade. We probably have an opportunity to go a little bit higher than that, but it's not going to be the same as what you would see in high-grade disease. I think that's the right decision. I do think that urologists are actually more price-sensitive than oncologists are. They're going to weigh that as part of their decision.
We will make sure that our pricing doesn't put us in a situation where anybody will limit the use of our product because of the price. At the same time, 80%, as Mark said, 80% durability, 80% CR. Most of the patients, I think we have the opportunity to price it with the value that we'll bring to patients, to physicians, and frankly, to the health care system.
How about reimbursement? Could you get a permanent J code in that January 1 timeline? I think you'd have to submit by July, right? That'd be right after approval. Is that something that you?
They will be ready to go, and it will go in before the end of June. We can get the J code by January 1, right? That is the expectation. Our expectation is that it will take six months, and we will have that permanent J code by January. You will still have some physicians that will use it in the first six months. They will definitely be much more comfortable after that. We have programs in place. We will bring extended dating so they do not have to pay us for more. It will give them more time in the beginning to pay us because it takes them longer to get reimbursed. We have a lot of programs that really surround our launch to make sure that physicians do not feel like they are taking too much risk.
Okay. I guess long-term risks, we can talk about if you envision any competitive risk or into the 2030s generic risk.
Great question. From a competitive, I always say I think I'm weird in a sense. I love competition, not in the sense of because I want to compete against them. We have to remember you're treating cancer, and you're not curing cancer. Because we're not curing cancer, these patients need more treatments. I'm all for other companies coming in and providing more treatments. I'm all for us providing more treatments as we talk about our pipeline. These patients will cycle through medicines. I also think that multiple companies out there talking to surgeons about using these pharmacologic interventions instead will grow the market. We talk often about, I say the low-grade market's about $5 billion. That's being very conservative. There is room for competitors. I'm actually very happy to have others.
Generic, the situation that we're in is we have our patent protection until 2031. We also have a next-generation formulation that we have that has some benefits from manufacturing and solubility, so a preparation benefit. We're doing the studies on that right now. We expect to launch those prior to our patent expiry. Those patents actually go to 2041. We think we have right now in our current portfolio a long life cycle. We've been adding, we want to continue to add to our portfolio so that we can build a long-term sustainable practice.
Okay. One more follow-up on that because I know we are starting to get limited on time. If there were a therapy that was sometime down the line approved in the adjuvant setting, like used with or at the time of surgery, how would that change the market for UGN-102, if at all?
Yep. Mark, I was going to ask you as a physician.
Yeah. I think one of the things you have to remember about this market in particular is these are people who, most of whom, as Liz has said, have already had a TURBT. They've had surgery, and they've recurred. They've effectively failed primary therapy, as we understand the standard of care. The attraction of having more surgery is diminished in this population. We know because we've asked these people how they feel about it. I think in terms of our impact on the market, our opportunity, a primary nonsurgical therapy is going to be very appealing to a lot of people. I also think, as Liz pointed out, having more people concentrating on this conversation and bringing medicines to various phases of care only increases our opportunity to take better care of these patients, which is an opportunity in and of itself.
Okay. I know we're closing in on time here. We didn't get to all of the other programs. I know you touched on the life cycle ones that you are working on. Can you talk about the newest addition to the pipeline first and then?
Sure. Yeah. Mark likes to talk about it.
Yeah. We're excited to expand our horizons. As some of you may know, we have a program currently in immuno-oncology delivering an anti-CTLA4 antibody to the bladder directly, which is unique in our platform technology. Last week, we announced the purchase of an asset from IconOVir called ICVB-1042, which is an oncolytic virus with some very specific characteristics which make it very attractive in the near term for application to the urinary tract. It has very selective replication once incorporated into the tumor cell and sparing of normal urothelial cells. High specificity, high potency. We will be doing IND enabling studies this year and look forward to bringing that into the clinic after that. It's early days for this program, but we are excited about expanding our efforts in high-grade disease, which is another area of interest.
This asset, interestingly, also offers opportunity to expand beyond the urinary tract. We will be exploring those at later dates as well.
Okay. Thank you. I guess one more question is, what do you believe is the most underappreciated aspect of UroGen by investors?
I'd like to say everything. But if you look at it, unfortunately, our market cap today, we're not getting credit for UGN-102. I think it doesn't take a lot on the back of the envelope for UGN-102 to be a billion-dollar drug. I mean, you would have to have less than a 20% penetration in the recurring-only patient population to get to over a billion dollars. I think anybody who talks to physicians in this space are excited about this opportunity. I do think that the overhang of the ODAC and the upcoming submission is there. We're not getting credit for UGN-102 and the opportunity today and then the opportunity to have this for a long time. I think it has to be the fact that we're on the cusp of getting that approval. I think that's the biggest underappreciation.
Do you have anything to add, Mark?
No.
That is great. I mean, we are a little bit over on time. We will close it out there. Thank you to both of you, the rest of the UroGen team who is here, and everyone here who is listening. Appreciate you.
Thanks, Sarah. Thank you.