Good morning, everyone. I'm Tara Bancroft. I'm one of the senior biotech analysts at TD Cowen. I want to thank you very much for joining our sixth annual Oncology Innovation Summit. To start off the day, the first session, we have a Q&A with UroGen, and it's my pleasure to introduce Liz Barrett, the President and CEO, and Mark Schoenberg, the CMO. It's a privilege to have you both here. Thank you. Thank you for being here with us.
Thank you for having us.
Yes, of course. Before I get started, I do want to remind anyone who's listening that you can email me questions at any time at tara.bancroft@tdsecurities.com if you have a question, and I'll make sure it gets answered. I think a really good place to start, Liz, and then Mark, I want to hear both of your thoughts, and we'll get into details. Maybe at a high level, could you give us your thoughts, your reaction to the ODAC meeting that was hosted last week and how the vote went?
Great question. Actually, I'm going to flip it and let Mark answer first, and then I'll come back and add anything. Mark.
Yeah, thanks. Good morning, Tara. Thanks for having us. The format of the meeting, for those who didn't have a chance to listen in or read the transcript, was the following. We presented a data set that had actually been agreed upon prospectively with the FDA regarding our total programmatic experience with a drug called UGN-102 for the treatment of low-grade, intermediate-risk non-muscle invasive bladder cancer. The agency had specifically asked us to present efficacy data in the subset of patients we'd studied across the program with recurrent disease, which was the highest unmet medical need. We had talked to the agency about this. In addition to our presentation on that, we had a total programmatic presentation on safety. Prior to our presentation, the agency presented a background talk on non-muscle invasive bladder cancer. We presented, then the agency presented their perspective on our data.
There were two questions that the advisory committee was, well, there was one question and one discussion question. One voting question and one discussion question the advisory was asked to consider. The specific voting question had to do with the benefit-risk of our drug in the context of treating non-muscle invasive bladder cancer. The discussion question was quite different than what we had originally anticipated, and it was specifically to address, in a more or less academic manner, the value and need for randomized clinical trials in the future in the setting of treating non-muscle invasive bladder cancer, which is an area of interest for a lot of people in our field, including the FDA, but was, frankly, quite disconnected from the matter at hand in considering UGN-102. After those data presentations, there were relatively few questions about our program.
We broke, came back for clarifying questions, and then a discussion was conducted, which largely focused on the merits of randomized clinical trials. There was relatively little discussion of our program or the data. To be very specific, the advisory committee was composed predominantly of medical oncologists, a biostatistician, two guest urologists as temporary voting members, an industry representative not a voting member, and a patient advocate. Interestingly, in the midst of the conversation where the clinical trials question was discussed, Dr. Pazdur interjected, just to direct the overall proceedings, to remind everyone that the discussion question was not relevant to the consideration of UGN-102 or our application.
There was then a vote, and it was very clear, based on what came out of the vote, I think for those who were listening, that the discussion question had materially influenced many of the members of the advisory committee, particularly the medical oncologists, who were obviously very interested in the question of clinical trials in general. The urologists both voted to support the approval, as did the patient advocate and one of the medical oncologists. When asked, and Liz will, I'm sure, want to comment on this as well, when asked why people voted no when asked to consider the benefit-risk question of UGN-102, almost to a person, the voters referenced the fact that randomized clinical trials were necessary, even though the single-arm trial that had been presented was prospectively agreed upon with the agency as supportive of an approval.
Let me stop there because I've said a lot, but I think that was my sort of composite impression of what happened. Just one final note. In the discussion, when FDA was asked what a randomized trial would look like in the context of studying non-muscle-based bladder cancer, the FDA could not answer the question directly, but said it would be a matter to discuss with the sponsor at the time such a trial would be designed. I know Liz is going to probably want to comment on this as well, so let me stop talking now.
Thanks. I do think that's sort of the key question here. I think that there was a little bit of misunderstanding of actually what we did, because we actually did offer a randomized control study. They talked about the feasibility of a randomized control study. That was never the issue. The issue was agreeing on an endpoint in a randomized control study. We offered a placebo-controlled study. We offered up a non-inferiority study, but the agency would not agree to that and would only agree to a superiority study. Oh, by the way, in the superiority study, they did not want the three-month, if there was a recurrence at three months in the TURBT arm, they did not want that to be an event. It felt like we were, you know, the whole trial was being stacked up for failure.
In our case, do you continue with a study that you, you know, that the FDA has already told you they don't agree with the endpoint, or do you, you know, try to find another path? That is when we got agreement with them that a single-arm study could be the basis for an approval. I don't think that came out in the ODAC, that we actually were willing to do a randomized control study, but not a superiority randomized control study, because no sponsor had ever been required to demonstrate superiority to a surgical procedure. The complexities of, you know, of actually showing a medicine therapy versus a surgical medicine, I think everybody understands sort of the challenges with doing so.
Look, at the end of the day, I think we feel like, you know, we feel like we have a path forward. We have to work closely with the FDA to see where we go from here. We were, you know, reassured when Dr. Pazdur did say, "This is a split vote, and let's talk." That is kind of where we are right now. You know, we've reached out to the agency about having that discussion. We plan to continue, you know, every path that we can see, because our goal is to get an approval for UGN-102 on, you know, June 13th, which is our PDUFA date.
Okay. Yeah. Thanks for those thoughts, both of you. I guess before we get into more details on Pazdur's comments, path forward, I think one of the things that is so confusing about this is really why you think they maybe why they wanted to do this unrelated discussion question, because it very clearly did confound the committee. What do you think the goal was for having that discussion if it doesn't pertain to the 102 review?
Yeah. I mean, personally, I would prefer not to speculate. Given where we are in the conversations with them, to Mark's point earlier, I do think that the vote was an unintended consequence of that discussion. I do not think that the FDA purposely wanted to confound the question, but having that discussion right before you take a vote on a single-arm study probably, you know, was not the best, you know, setup, at least not for us. You know, at the end of the day, I think we know that the FDA's role is to challenge, to ensure that medicines that are efficacious and safe are delivered to patients. We feel like we did that, frankly, with a very high bar. I mean, I have been in oncology for 30 years, and never have I seen an 80% complete response rate and an 80% durability.
To not take into consideration the compelling nature of our data, I think was shortsighted. You know, again, our goal, we have one goal, and that goal is to get UGN approved. If we have to do post-marketing to talk about safety or to show, you know, continued durability, if that's the question, we've agreed, we already agreed, and we already planned a five-year follow-up for ENVISION. That will continue to give more data on both durability and safety if there are still questions. You know, I think, you know, again, we probably shouldn't speculate on what the FDA was thinking at the time. You know, we want to work in partnership with them. We want to find a path forward and are looking forward to having those discussions.
Okay. Yeah. You know, I think I want to get into a little bit more detail on Pazdur and his role and stuff, but since you just brought up the five-year ENVISION study or the ENVISION follow-up, and that as a possible scenario, I think what would be really helpful is to kind of go through what you envision as the possible scenarios that could come from this. Like, what are the next steps? What do you think the likelihood is of each?
Yeah. Mark, do you want to comment about that? And then.
Yeah. I mean, I, you know, I'll give you my thoughts, and obviously, Liz will reflect on this as well. Obviously, you know, we are hopeful that we'll get full approval with some kind of a reasonable post-market commitment, for example, acknowledging the fact that we've already structured ENVISION to provide very long-term safety and efficacy data supporting our contention that this is a reasonable alternative to surgery in this population. We can conceive of other iterations of this that would include possibly the commitment to some form of a randomized trial, either with the current agent or with the successor agent that we've talked about publicly, 103. I suppose that there probably is a possibility, because the FDA has the latitude to do this theoretically, to provide a conditional approval analogous to accelerated approval contingent upon some additional clinical trial work.
I'll stop there. Liz may want to comment on that as well.
No, I think Mark's right, but there's so many different options. To your point, it's hard to sort of peg without, you know, having more discussions, you know, with the FDA on where they see this going. I think for us, you know, having to do a randomized control study before an approval is not really an option for us. We really need to find a path forward that allows us to have an approval. Again, we think if there's going to be a focus on post-marketing, it should be on safety. It should be understanding the natural history of the disease. At the same time, we'll be open-minded to whatever, you know, comes forward as long as we can get an approval, you know, prior to that study having to be done.
Yeah. For the RCT, let's, I mean, we can spitball some potential different options, but I mean, it seemed like from the discussion, you know, the history that you guys have had with your engagements and what they were discussing at the ODAC, what do you think, I mean, if they require an RCT post-marketing, do you think it will be a superiority study, non-inferiority? I think one thing that was very clear is that that's really difficult to agree upon, even if you get a conditional approval. I'm curious to think, what do you think that would look like?
Yeah. The only one that I can think of would be an adjuvant study, which would be very unfortunate. The reason that would be very unfortunate is because one of the greatest benefits to our drug is you got an 80% complete response without having surgery. And we all know, you know, the complications that can occur with surgery, even though they may be a small percentage, do you want to be the one person that has your bladder perforated, right? Do you want to be the one person that goes back to the hospital? It is very unfortunate if that's the case, but I don't see any other, to your point, what doesn't go away if we do a randomized control study is what is the endpoint? You know, what do you have to demonstrate?
How do you do it versus surgery when you have a surgical procedure where you get a CR at Day Zero, and then you have a therapy where you get their complete response at three months? You know, how do you reconcile that, you know, from a statistical standpoint? I think that's the biggest challenge. The challenge of the endpoint doesn't go away if we have to do a randomized control study. It's unfortunate for patients, frankly. Does it matter to us whether it's an adjuvant or not? Not so much. Boy, it matters to patients. You heard the patients at, you know, you heard the patients there at the ODAC. That's typical. That's not like those patients are unique. That is typical of what we hear from patients who have gone through both.
In the patient-reported outcomes and in the work that the UNC did, that came out loud and clear. When 90% of patients say they preferred, and they've all had a TURBT, they would prefer the treatment with UGN-102 over having another TURBT.
Yeah. No, I completely agree with that. Mark, one of the things that you said in that response that I just kind of want to go back to, you said, correct me if I heard this wrong, that it might be possible to use UGN-103 as a phase III that could be used post-marketing. Did I hear that wrong?
Again, I'm speculating, because, of course, as Liz has pointed out, you know, really, this is contingent upon conversations that we have not yet had with the FDA. As Liz has said many times, you know, publicly, we have a successor molecule, the UGN-103, which is another formulation of mitomycin using a proprietary methodology that we will be advancing as the successor to UGN-102, and which is currently in clinical trials now on the basis of conversations and implementation agreed upon with the FDA. It is, I suppose, theoretically conceivable that we would arrive at an agreement whereby, given the fact that 103 is already in advanced stages of clinical trials, it might make more sense to focus on the development of 103 in the context of a randomized trial.
Were we to agree to do one and what, you know, again, I don't have the details for what that would look like. Again, Liz, do you want to chime in here?
No, agree. I mean, I think until we have those conversations, until we know where we are, you know, it is speculation, right? I think, you know, we hope to have a very productive conversation with them. We hope to have an exchange with them very shortly and look forward to that. Again, with our goal being, you know, we agreed with the FDA that the single-arm study could be the basis for an approval if it met certain criteria. We feel like we met and exceeded that criteria. That is kind of where we are at this point.
Uh-oh.
I think our monitor.
Hi. Sorry about that. We've been having some problems with Zoom at TD, but okay. Yes. No, that definitely makes sense. I understand you guys, you haven't met with them. It's really hard to speculate ahead of actually having that meeting. I think one of the things that kind of begs the question is, like, can you meet with them in the next two, three, you know, before June 13th, basically? You know, I'm just trying to get an idea of, like, what you would think if you can have these discussions, plan an RCT ahead of the PDUFA date. If not, you know, maybe they'll issue a PDUFA delay. You know, what could that possibly look like?
Yeah. I mean, look, there's lots of different scenarios, like we talked about before. I think, again, I think we will be able to engage with them. It's hard to say whether it be a meeting, whether it will be an exchange. I think it really depends on what their position is. We absolutely have time. You know, we, as you've noted before in your write-ups, we had already been talking to them about the label. So, we're pretty far along from that standpoint. The missing piece is sort of the final labeling, as well as what does a post-marketing, you know, post-marketing commitment look like. I think we could get that done if they're willing to engage with us. Again, engagement can be a lot of different ways. That's our goal.
Our goal right now is to have that dialogue, whether the dialogue is a Zoom call or whether it is in person or whether it is just an email exchange. It really depends on, you know, kind of what their viewpoint is. I think we will be, again, working, wanting to work with them very productively and ensuring that we can get an approval. If there has to be a delay, I, you know, I do not foresee that, but if there has to be a delay so that we can come up with something, you do not have to have the post-marketing trial done. You do not have to, you just have to have a framework agreement. It does not have to be all of the details. It just has to be, again, a framework agreement.
I think from that standpoint, we have the time, if they're willing to engage with us, to get that done. You know, that would be our goal.
Okay. Yeah, that definitely makes sense. Okay. I know we have about five minutes left. I think one thing that people are playing and replaying and going back over a lot is Pazdur's comments. There are a couple of components of this that it would be really helpful to get your thoughts on. One is, how much influence does he have in this decision? What did you make of his comments during the ODAC?
Yeah. I mean, look, and I'll ask Mark to comment as well. Again, we would be speculating. I can tell you that I think that the FDA, I think the healthcare system, I think patients in general are very fortunate to have someone like Dr. Pazdur. He is someone who has been very, you know, he's been very involved in all of the cancer treatments. I mentioned earlier, I've been in cancer for 30 years. He's been very involved in ensuring that the right medicines get to patients at the right time. I've been in situations where, you know, drugs have been pulled off and then brought back on because patients needed them. I personally am very happy that he's leading the oncology division. I don't know him personally, but, you know, obviously we'll have and we'll interact with him.
Again, I don't want to speculate on Dr. Pazdur. I think it was, you know, we were reassured by his comments that, one, it was a split vote, but two, trying to lead the group to understand that it was not a, that we were not talking about this application and then following up. You know, we, you know, believe, obviously, he has influence. What his willingness is to engage, you know, is yet to be determined. Again, have a ton of respect for him and believe that, you know, ultimately he'll do the right thing. That's our hope.
Okay. So then, I guess another thing that we're all trying to wrap our heads around, and again, it is a speculation question. The possibility for a potentially limited label. If the label is restricted to patients that are either TURBT ineligible, patients with comorbidities, what would that look like? Does that change your outlook for either the initial launch or the peak market at all?
Yeah, I think it depends, right, on what that label is. I find it to be difficult to have to do that. The reason I find it difficult to do that is you have to look at our clinical study and what data came out of the clinical study. The clinical study wasn't, it was pointed at a patient population where, you know, the majority had had one or two TURBTs. To try to limit it to those who had more, and to try to limit it, it wouldn't really be reflective of the clinical data. Now, could they? Sure, they could. I think it depends. I mean, if it had unwilling and unable, you know, to go through a TURBT, patients then can make that decision. Physicians can make that decision.
If it were, you know, relegated to those that have two or more, you know, as we know, we have 68% of the patient population have had two or more TURBTs, you are talking about 68% of the patient population. Having said that, we always expected that, you know, our, you know, drug will initially get used in those patient populations. It does not really change our outlook only if it were very limited to patients that had, you know, a specific comorbidity. That would be, I think, the only way it kind of would limit the potential of the drug to reach more enough patients and the patients that actually need it. That would be the only way it would be very limited.
Yeah. No, definitely makes sense. Since it is my fault that I had technical difficulties, I want to ask one more question. I know you mentioned before that you have the medical liaisons and your field team out in the field already. I am curious, as they have been at work over the last week, what are they hearing from any feedback from urologist colleagues on what they think about what happened and their support or not support for UGN-102's approval and/or use?
I'm going to ask Mark to comment because he personally engages with a lot of urologists. As you guys know, he's still a practicing urologist, but even though he knows that, and I think he has a lot of insight into what the community is thinking. So, Mark.
Sure. I think the best single-word capsule summary of this is disappointment. I think as reflected by the comments on the urologists who were serving on the adcom who were supportive of this, if you work in this field and you understand the nuances of this disease, UGN-102 makes complete sense, and the data are incredibly compelling. For the urology community, the response of the adcom is really not aligned either with practice or patient needs. I think that was the sense I got from many notes sent to me immediately following the adcom expressing astonishment at the outcome.
Yeah, I would use shocked as well as disappointed too, because I think that it was very unfortunate. I do think the urologists, to your point earlier, that were on the panel, that they understood. I do not think that the others did. It is unfortunate for our company, of course, but it is really unfortunate for patients.
Yeah, I agree. You know, we all wish you luck in your engagements going forward, and we will obviously all be on the lookout on the PDUFA. Hopefully, we will talk to you soon. Thank you for joining us, and thank you, everyone, for listening.
Thank you.
Thanks, Tara. Take care.
Bye-bye.
Bye-bye.