Good morning, and welcome to the UroGen Pharma Q&A webinar. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this call is being recorded, and a replay will be made available on the UroGen website following the conclusion of the event. I'd now like to turn the call over to Vincent Perrone, Senior Director of Investor Relations. Please go ahead, Vincent.
Good morning, everyone. As Tara mentioned, my name is Vincent Perrone, Head of Investor Relations for UroGen Pharma. I'd like to welcome you to UroGen's Key Opinion Leader webinar for investors and analysts. The topic for today's webinar will cover the unmet need and treatment landscape for Non-muscle Invasive Bladder Cancers, or NMIBC, with a focus on low-grade intermediate-risk NMIBC. Next slide. Before we begin, let me remind you that during today's call, the company will be making forward-looking statements concerning future events, including, but not limited to, statements regarding our intentions, expectations, and beliefs regarding our product and product candidates, our ongoing clinical trials, and our business operations. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and are subject to assumptions, risks, and uncertainties that could cause actual outcomes to differ materially from those contemplated in these forward-looking statements.
In addition, any forward-looking statements represent the company's views only as of the date of this webcast and should not be relied upon as representing the company's views as of any subsequent date. A description of potential risks and uncertainties can be found on slide two of the presentation and in our latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and UroGen disclaims any obligation to update these statements. Next slide. We have about an hour scheduled for today's webinar, and we'll be working our way through the following agenda, which outlines opening remarks from Liz Barrett, Chief Executive Officer of UroGen Pharma. Mark Schoenberg, Chief Medical Officer of UroGen Pharma, will introduce Doctors Hwang and Steinberg, who will each speak for approximately 10-12 minutes.
Mark will conclude with an update on the UGN-102 phase III ENVISION study before moderating a 20- to 30-minute Q&A session. At this time, I'd like to turn the call over to Liz. Liz.
Thank you, Vincent. Hello, everyone. Next slide, please. As you've heard, we're here to talk about UGN-102 and importantly, the landscape of Non-muscle Invasive Bladder Cancer. As many of you know, and we've shared before, this is really in response to a high unmet need in the area of urothelial cancers. Before, prior to UroGen, the invasive and radical surgery is the standard of care currently in urothelial cancers, making it challenging for physicians to treat. Why? Because of the anatomical barriers associated and the inability for medicines to dwell long enough in the cavity to actually have a meaningful impact. What happens is these patients go through repetitive risky surgeries, they oftentimes lose their kidney or other organs, and there's an increased risk of morbidity in elderly patients. Next slide, please.
Because of this high unmet need, a group of chemists in Israel actually developed the RTGel. RTGel is a proprietary reverse thermal hydrogel technology uniquely designed to allow for local delivery of medicines and in direct response to physicians calling out this unmet need in the area. As we talked about before, it increases dwell time, allows for drugs to be longer in the cavity and hopefully improving the therapeutic effect. Next slide. As we think about UGN-102, let me remind everybody it's an investigational non-surgical treatment for low-grade intermediate-risk Non-muscle Invasive Bladder Cancer. It utilizes the RTGel technology that's proprietary to UroGen, and it delivers mitomycin very similar to our current JELMYTO that is on the market.
As I mentioned before, it exists as a liquid when it's chilled, and as it hits the warm temperature of the body, turns to a gel and allows for medicine to be delivered over a several-hour time period. It's intended to reduce the recurrence and patient burden associated with TURBT, and you're gonna hear a lot about that today, so I won't go into that. If approved, UGN-102 would be the only primary intravesical chemotherapeutic chemoablative treatment for low-grade intermediate-risk Non-muscle Invasive Bladder Cancer. Importantly, it's 96% of urologists that we in our survey said that they would use UGN-102 within two years of approval. Next slide.
As I've mentioned before, there are a lot of similarities between our current JELMYTO and UGN-102 in the sense of and Mark, and I'm sure doctors can also comment on this, that the disease in the upper tract urothelial cancer and as well as bladder cancer are really a similar cancer. What we've seen in our results so far, our clinical results, that in the phase III OLYMPUS study for JELMYTO, we had a 58% complete response rate and about an 82% duration of response by Kaplan-Meier analysis. Similarly, with UGN-102 in our phase IIb OPTIMA study, a 65% complete response rate and a 72.5% duration of response. What this tells us is that they work similarly to each other.
As I mentioned, the molecular profiling shows that these two diseases are very similar, giving us a nice proof of concept using gemcitabine and the phase 2 study for UGN-102, giving us a high confidence in the results of the upcoming phase III pivotal study. Next slide. I do think it's important, though, to notice the similarities but also the distinct differences, and in this case, hopefully advantages of UGN-102 over gemcitabine. It's really the same method of delivery, as I mentioned. It's mitomycin and RTGel, although they are different drugs. They're different because the ratio of the medicines is different, and the volume is different because you need a much, much bigger volume for the bladder than you do the upper tract.
As I mentioned, similar diseases, similar results, and synergies from a commercial standpoint because about 95% prescriber base is the same for JELMYTO and UGN-102. The distinct differences are that the UGN-102 is a much simpler medicine to give to patients. It's a simpler administration because you're not manipulating the upper tract. You don't have to get to the upper tract, so you don't need fluoroscopy. You don't need certain equipment, other equipment that you don't need. The installation is a routine, simple procedure that can be done in the clinic and be done by a doctor, or it could be done by a nurse or an extender. Importantly, as we've talked about before, the market for bladder cancer is obviously much bigger than the market for upper tract.
Next slide. This gives you an example of it's a $3 billion+ market if you had all patients in this low-grade, intermediate-risk Non-muscle Invasive Bladder Cancer. About 80,000 patients annually in the U.S. alone. About 60,000 of those patients are what we call recurrent patients, and the current treatment today is a TURBT or transurethral resection of the bladder tumor, which you're gonna hear a lot about today. Again, the characterization of the intermediate-risk patient is characterized by multiple tumors. Large tumors greater than three centimeters are the actual recurrence and the fact that these patients continue to recur. With that introduction, I'm gonna turn it over to Mark Schoenberg to introduce our physician panel today. Mark?
Liz, thank you, very much and good morning, everybody. It's a real pleasure to have two esteemed colleagues join us this morning to talk about the treatment of urothelial carcinoma and specifically about the treatment of low-grade intermediate-risk disease. Dr. William Hwang is the vice chair and co-director of robotics in the Department of Urology at NYU Langone Medical Center, and Dr. Gary Steinberg is the director of the bladder cancer program at NYU. We are lucky to have them. They are experts in the management of this disease, have experience with UroGen's products, and we look forward to their presentations and the Q&A. With that, let me go to the next slide, please. These are the faculty disclosures which are included in the slide deck.
Let me then turn the podium over to Dr. Hwang, who will be the first to present. Bill, the floor is yours.
Good morning. Thank you. I'm gonna give a brief background on bladder cancer basics, and then also describe the unmet needs for these patients with bladder cancer. Hopefully you can hear me. Next slide. Next slide. As you previously heard, the urinary tract is really divided into two locations, the upper tract, which is the kidneys and the ureters, as well as the lower tract, which is the bladder itself. As many of you may know, a similar product, JELMYTO, is used to treat the upper tract, and UGN-102 is being used to treat the lower urinary tract, which is the bladder. The entire urinary tract is covered with a lining which is similar to the skin on the outside of our body, and it's this lining that develops bladder tumors or urothelial tumors. Next slide.
Some key facts to recognize is that bladder cancer is extremely common, unlike its counterpart in the upper tract, with over 80,000 cases diagnosed per year. This results in about 17,000 deaths per year from bladder cancer, making it the second most common urologic malignancy. It happens more commonly in men with a 4-to-1 ratio, and it essentially results in over 700,000 people in the United States living with bladder cancer today. Next slide. How we determine the management of bladder cancer or all urothelial cancers really is dependent on the grade and the stage. You can think of grade as how aggressive this particular tumor is. There are two grades that we give to urothelial cancers, which include low-grade versus high-grade.
Low-grade tumors are tumors that appear relatively normal or look similar to the way normal bladder cells look. Whereas high-grade tumors are abnormal appearing and have a propensity to invade and potentially spread. Next slide. If the tumor does demonstrate any invasion, then this changes the stage of the bladder cancer. Stages are really broken down into two parts. You have Non-muscle Invasive Bladder Cancer, which is a bladder tumor that's only on the surface or invades only into the first layer of the bladder wall. You can hit the next slide. You have muscle-invasive bladder cancer, which results in invasion even deeper into the bladder wall into the muscle, and that is managed completely differently than the way that we would manage low-grade or Non-muscle Invasive Bladder Cancers.
Again, the management of bladder cancer is highly dependent on the grade and stage of the tumor. Next slide. Next slide. As you may have heard, the way that we manage bladder tumors initially, irrespective of whether it's low-grade or high-grade, is through transurethral resection. A transurethral resection is the insertion of a metal tube or rod into the bladder through the urethra, and then that instrument is used to resect the tumor. If we could show the video of this. As you can imagine, since this is a metal rod that's inserted into the bladder, this needs to be done under anesthesia, and there's a hot electrified loop at the end of the instrument, and it's used to shave the bladder tumor down.
Now, since this procedure is the hallmark of treatment for bladder cancer, this results in patients who are frequently older and sicker having to go to the operating room to undergo this procedure. Not surprisingly, this procedure is associated with the risk of complications, including pain and urinary symptoms from having the instrument inserted. In addition, there's a risk of bleeding. As you can imagine, the bladder is well vascularized, and many of these patients are older and are on blood thinners, increasing their risk of having bleeding complications. In addition, there's a risk of infection as well as injury during the actual procedure itself. We can show you an example of how easily an injury can happen to the bladder during a transurethral resection. If we could show the next video.
This is a bladder tumor that's very close to a nerve in the pelvis, and you can see that that easily can result in a perforation through and through of the bladder during this routine procedure. One final thing to take into account as well is that these patients require lifelong surveillance and frequently require treatment over and over again. That's because up to 60% of patients will have a recurrence within a year, and up to 80% of patients will have recurrences after five years of their initial treatment. This is a procedure that frequently has to be done in patients once they've been diagnosed with bladder cancer. Next slide.
Now, there's a particular cohort of patients or group of patients that we're gonna focus on because these patients have a propensity to recur, frequently within a year, or they have larger tumors over three centimeters, which are low-grade. These are patients that are primarily diagnosed with frequent recurrences and therefore is exposing them to the need to have recurrent treatments throughout their lifetime. The unmet needs are providing them with additional treatment options that we can do besides the repeated surgeries, as well as reducing the chance that they're gonna recur, which happens frequently. From here, next slide. I'm gonna conclude with the fact that bladder cancer is a common cancer affecting over 700,000 Americans. Most bladder cancers are actually low-grade and non-muscle invasive, which is a good thing.
However, these patients are at lifelong risk of recurrence and repetitive treatments. The standard treatment that we have, even 50 years after initially undergoing treatment for these and even longer, is TURBT. There's a significant unmet need for these patients with Non-muscle Invasive Bladder Cancer. I'm gonna turn it over to Dr. Steinberg.
Thank you, Bill. Can everyone hear me?
Yes, we can.
Thank you. I'm gonna talk a little bit about treating intermediate-risk Non-muscle Invasive Bladder Cancer. Next slide, please. For patients with Non-muscle Invasive Bladder Cancer, the standard of care is to try to completely remove the tumor with the operation as Dr. Hwang just outlined. Adjuvant therapy for all patients, well, that is a bit debatable, especially now that we have a BCG shortage. We clearly have moved away from using intravesical BCG, which is immunotherapy in the bladder for patients with intermediate risk disease. As also Dr. Hwang outlined, many of these patients are elderly. They require family members, children, relatives to drive them to the office for intravesical therapy.
It is reasonable in these patients to not use any adjuvant therapy and just treat them with repetitive transurethral resections of bladder tumors, of which, as Dr. Hwang outlined, does have its risks and complications. There is a thought that you potentially can give one dose of chemotherapy into the bladder within 24 hours after a TURBT. It's thought to eliminate implantation of tumor cells. We'll discuss this a little bit later. I personally think that tumor cells don't implant that way. That's not the way biology of cancer works. There have been randomized studies demonstrating an 11.7% decrease in the recurrence rate using a single dose of chemotherapy after a TURBT, whether it's mitomycin C, doxorubicin, epirubicin, or gemcitabine.
However, it really only shows a benefit in patients who are at low risk disease. Those are patients with primary solitary tumors that are low-grade, typically small. These are what we call low risk, and low risk meaning low risk for recurrence and progression. Intermediate risk for recurrence and progression. Certainly, if you've perforated the bladder or you've thinned out the bladder too much, and some of these chemotherapy drugs are given after the TURBT, they can infiltrate through all the layers of the bladder and can cause some significant lower urinary tract symptoms that can last, if not, 6-12 months, even longer. Next slide. We also know that the TURBT is expensive. Mossanen et al.
constructed a Markov model to determine the cumulative cost of care over a five-year period of the surveillance of patients with Non-muscle Invasive Bladder Cancer. This is not talking about TURBT and intravesical therapy. This is just the surveillance. The Markov model estimates the five-year cost for low, intermediate, and high risk Non-muscle Invasive Bladder Cancer. For the intermediate risk, we can spend close to $150,000 just for surveillance with cystoscopies and cytologies and so forth. Next slide. Well, why do we use intravesical therapy? That's this medication we put in the bladder. Well, the rationale is it may prevent tumor implantation, which I don't believe in, because I don't think that's how biology works. Cancer cells don't just float around and then all of a sudden attach to certain parts of the bladder.
There has to be multiple molecular changes for that to happen. We do know that it has a subtle toxic effect against residual cells that we may not see. Potentially, it can cause immune cell death, turning on the innate and the adaptive immune system. However, as we know, there is T-cell exhaustion when you turn on the immune system too much. We know that by giving medication in the bladder, it's limited toxicity. However, we also know that there's limited efficacy because how much of the drug actually attaches to the cell wall.
How much it actually is absorbed and becomes effective, we believe is limited due to multiple chemical factors and physiologic factors, and that it's been re-estimated that when we use mitomycin C alone in solution, that we may only affect or have efficacy of 1%-2% of the drug that we've instilled and to the urothelium. We want to give the intravesical therapy to decrease recurrence and progression. Again, intermediate risk has an intermediate risk of recurrence and progression. Progression is maybe 2%- 5%- 10%. Recurrence, however, can be 50%-70% if not higher, if not treated. Chemoablation, which is a very important topic. It's actually going around.
There's a conversation on Twitter right now in the bladder cancer world about for patients who have had a recent myocardial infarction, and they cannot undergo anesthesia, to potentially put some intravesical chemotherapy in their bladder for chemoablation. Again, without data, without randomized prospective trials. It certainly is a concept that is readily available to urologists. As an adjuvant, 15% short-term decrease the recurrence rate, no change in progression. Multiple studies, over 6,500 patients, no drug better than others. There was a recent trial looking at heated mitomycin C versus standard intravesical mitomycin C, in intermediate risk patients used in an adjuvant setting. We saw very high recurrence rates in both groups. There was no benefit from the heated mitomycin C.
More importantly, it shows us the natural history is that when you use your standard intravesical chemotherapy, there is a very high likelihood of recurrence. Next slide. Again, just to reiterate, Dr. Hwang spoke about this, but the intermediate risk patients are patients who have recurrences within one year of low-grade, non-invasive tumors. They have solitary low-grade tumors greater than three centimeters in size, multifocal low-grade tumors. They have high-grade Ta tumors that are less than three centimeters in size. A first-time event, any high-grade recurrence would make it a high-risk tumor. Then low-grade T1, which is a tumor that superficially invades into the submucosa of the bladder but is still considered low grade. In the old days, we used to call those T1 grade twos.
I actually think that low grade T1 doesn't exist very commonly. Next slide. The intermediate risk patients are not straightforward to identify or treat. It's a heterogeneous population. There's a lack of independent studies comparing therapies. I mean, there's a lot of therapies that urologists use without any randomized prospective data. The uncertainty remains about the categorization of the patients. The current clinical guidelines vary. There's certainly a difference between what the guidelines say and what happens in the real world. In the real world, many of these patients do not receive any significant adjuvant intravesical therapy.
Many times, they're just treated in repeated trips to the operating room or tumors are fulgurated in the clinic, or some are just followed conservatively, especially the elderly patients, and we wait until the tumors get bigger. Next slide. Well, the primary chemoablation of low-grade intermediate-risk NMIBC with UGN-102, the OPTIMA II trial. These patients were treated with six weeks of UGN-102 once a week for six weeks. They were followed at three months. We looked at the complete response rate at 3 months, and then every three months after that, they had cystoscopies and cytologies. The secondary endpoint 12-month durability and safety. Total initially enrolled were 63 patients, 38 men, 25 women.
Again, bladder cancer is four times more common in men than women, so it's good to see so many women in this trial. The complete response rate, this is again, this is not adjuvant therapy. These are patients with tumors treated with chemotherapy as a chemoablation to avoid or eliminate the need for transurethral resection of bladder tumor. We've got a 65% complete response rate. Of those with a complete response, we see that the durability of the response is quite favorable. There are mild or moderate adverse events were common with dysuria and hematuria, which we see with any intravesical therapy trial. Next slide. This slide, it's a little difficult to see, but again, this is just showing the durability.
That of the patients with a complete response, when you follow them, at nine months or six months after their complete response, you still see 73% are disease-free. At 12 months or nine months after the complete response, 61% are still disease-free. Then there's no reason why if you've got a complete response and patients recur, that you can't retreat these patients. It'll, you know, do you need to retreat them with six weeks, or can you retreat them with one or two doses? That's something that I suspect the urologist will figure out fairly quickly. I think that the urologist will really gravitate to this therapy because it truly helps save patients time, physician time, and so forth. Next slide.
In conclusion, there was a recent study looking at enhanced cystoscopy, which is blue light cystoscopy, and I'm sure everyone's heard of versus white light cystoscopy. The very sobering finding of this trial was that at three years, there was no difference in recurrence rate in the blue light versus the white light. More importantly, what it shows us is that the natural history of the disease is that it's a field change defect of the urothelium, and that you have recurrences and that surgery alone is not gonna change that. What is clearly imperative is that we get better intravesical therapies. That's the only way we're gonna alter the natural history of this disease.
Again, that was a big conversation going on around Twitter on the bladder cancer world of late. There is financial toxicity. Every time you bring a patient to the OR, the family's gotta take time off, the patient's gotta take time off. They've got catheters. They're in the hospital. They've got to recover. There's a tremendous amount of financial toxicity of TURBT, especially in the elderly. We want to find a medication that's easy to use. There's no question that UGN-102 is something that every urologist is very comfortable doing in their office and do many intravesical treatments.
Then the other thing is that for the urologist in our healthcare system, as we're changing our healthcare system and physicians are being paid by relative value units. Every time they've gotta take half of a day to go to the OR and there's all the turnover and the RVUs for a TURBT, quite honestly, are not that high. It is a definite loss for the physician's practice if he's got to bring elderly patients to the operating room. And clearly it would be highly beneficial for the practice if they were able to use intravesical chemoablation in the office. And so there, I think I'm gonna sum up. I think I've given people plenty of things to discuss, and we'll go from there. Thank you.
Gary, thank you very much. I wanna thank both Bill and Gary for their summaries and very timely remarks. Really appreciate it. Before we go to the Q&A, just two brief comments I wanted to make, alluding or hearkening back to Liz's initial remarks. As she mentioned, and on the basis of the data that Gary presented, UroGen embarked upon a phase III program initially in a randomized trial of UGN-102 against transurethral resection. After a series of extended conversations with the FDA, we moved that program into what is currently the phase III program that is ongoing, enrolling now, and will be enrolled by the end of the year, which is the ENVISION program. A single-arm open-label trial, essentially exactly like the trial that Gary described, the OPTIMA phase II trial.
Again, that is in contrast to what was the original ATLAS trial. The data from the ATLAS trial actually are being accumulated. It is not fully enrolled, so it's a smaller population than was originally planned. Again, that's the randomized trial against TURBT. Safety data as well as some efficacy data will be available next year, and we will share that when appropriate. Next slide, please. This is just the study design of the phase III ENVISION trial currently enrolling internationally 220 patients. As Gary described, weekly dosing through a period of six weeks with UGN-102 for patients with intermediate risk low-grade non-muscle invasive disease, all of whom will have had prior experience. All of these patients are recurrent patients.
We expect full enrollment this year, follow patients next year, plan submission for approval in 2024. Very exciting, and we're very enthusiastic, as was mentioned, largely because this trial is so similar to the phase II, the results of which you just heard about. With that, let me stop and turn this over to the LifeSci team for Q&A. Thank you.
Great. Thank you, Mark. At this time, we'll be conducting a question and answer session with our speakers. Our first question comes from Chris Howerton from Jefferies. Please go ahead, Chris.
Hey, thank you. Thanks again, really appreciate hosting this event. The question
Chris, it sounds like you're breaking up a bit.
You start off the physicians is the lack of randomized data in this. Can you hear me at all?
You're fading in and out, Chris.
Got it. Well, question is, how do you anticipate treatment setting do you anticipate UGN-102 being used the most.
You know what, Tara? I think I heard enough of Chris's, so I'm gonna re-ask it for him. Maybe, Bill and then Gary, you could respond in turn, giving your answers to the question. The first, I think part of Chris's question is, given the fact that the phase III ENVISION trial is a single-arm trial, do you believe that the lack of randomized data against the standard of care control will significantly impact adoption and the perception by urologists who would be users of this medication for appropriately selected patients? Bill and then Gary, could you respond to that?
I personally don't believe that the lack of randomized data would significantly alter a urologist's or a physician's decision to use this drug. I think that's partially based on the fact that the alternative would be transurethral resection, which urologists perform. In many cases, we are trying our best to avoid having to do that. In addition, I think that urologists are very comfortable using agents that are done intravesically and didn't necessarily have randomized data in the past historically to compare it to prior to using a drug such as this.
Thanks. Gary, what do you think?
I think the patient population is huge, and this is a very common problem for every urologist. I think that there is plenty of historical data. I think that every urologist knows what the recurrence rate is of these patients. If they can avoid 50% of their TURBTs, they'll be thrilled. I think that the urologist will very quickly adapt. They will be able to predict which patients will benefit most from this. I suspect that, you know, again, you know, we talk about a complete response. If you get a patient and you give them UGN-102, and you don't get a complete response, but you get 90% response, and that the rest you can just fulgurate in the clinic, that's a big win.
I think that urologists are gonna gravitate to this very, very quickly. I don't think that the lack of randomized controlled trial will be a problem. Urologists, unfortunately, are used to doing a lot of non-randomized trials and publishing a lot of non-randomized data and readily adopting information, so.
Thank you. That certainly is an accurate characterization of the current state of practice. I think Chris wanted to know who the right patient is for this and how you would characterize that individual. I think we've talked a little bit about what the guidelines are for or at least the current characterization intermediate risk is. Who do you think this is gonna get used in? Gary, do you wanna go first and then Bill?
Yeah. I think any elderly patient with low-grade papillary appearing tumors, whether it even for a primary event, even for somebody, quote-unquote, "low risk," I suspect that to avoid a trip to the operating room, it'll be utilized. I think that this is a huge number of patients with low-grade Non-muscle Invasive Bladder Cancer, which makes up at least half, if not more, of the newly diagnosed bladder cancer patients in the United States.
Thanks. Bill, any thoughts?
Yeah, I definitely agree. I think this is really a great treatment option for those patients who are older, who have a history of having repeated tumors, and those are low-grade tumors that we often see in our clinic. As I mentioned in the basics, up to two-thirds of patients will have recurrences. This is a very, very common patient population that we're all used to dealing with.
Thanks very much. Let me turn it back to you, Kara.
Chris just had a follow-up question. He was wondering what setting is more likely to use given surgeons wanna perform surgeries.
Bill, why don't you go and then Gary.
Well, although surgeons may wanna perform surgeries, this is not a surgery that any of us want to willingly perform, in this patient population. I didn't really get into specifics about this patient population, but as I mentioned, they're elderly. They have a lot of medical conditions, and taking them to the operating room is hard, both on the surgeon, as well as on the patient. This is definitely not something that surgeons are enthusiastic about, spending their time as well as the patient's time, doing.
Yeah. I think that that's an excellent question. As you know, a lot of the reasons we do things in American medicine is by following the money. There's no question with the healthcare changes that we have, where the vast majority of physicians are now employed and not in their own private practice. The economics of taking these patients to the operating room is actually counterproductive. The urologist is more efficient economically by treating these patients in the office. I think that that's only gonna become more true as the healthcare system continues to evolve in the direction it's evolving. I think that there's gonna be a tremendous incentive for urologists to treat these patients in the office with UGN-102.
Great. Thank you for the questions, Chris. Our next question comes from Matt Kaplan from Ladenburg. Please go ahead, Matt.
Hi, good morning, and thanks for hosting this KOL call. Just wanted to dig in a little bit more to the ongoing phase III study, the ENVISION. I guess, given the strong results you saw with the phase II study, you know, 65% complete response rate and strong durability. I guess for the two doctors, what would you be looking for in the larger phase III that would get you excited in terms of complete response rate and durability, and for the ENVISION study when those results are announced?
I can go first. I think that if we replicate the results from phase II, I think that's acceptable. You know, I think that urologists will use this. Even in the patients that recur that have a, for example, a six-month duration of response, they may retreat. They may not retreat with another six weeks. They may retreat with one to two weeks, three weeks, and so forth. I think that you know, maybe some additional granularity in terms of the ENVISION trial, in terms of when patients recur, what do they recur with? Do they recur with, again, a tiny little tumor that can then be fulgurated?
I think that additional granular detail will be helpful and help define how this is used. You know, I suspect that the ENVISION trial will reinforce the benefits that we're seeing in the phase II trial.
Bill.
Yeah. I completely agree with Gary. I think having this phase 3 trial will just reinforce two things. One is the complete response rate as well as the durability, which I think are very important. I think another thing would be to demonstrate that it is well tolerated in a bigger population than the one that was in the phase IIb trial.
Okay. That's very helpful. One follow-up question, I guess, for Dr. Steinberg. You elaborated on the costs of TURBT and surveillance. How do you think UGN-102 could impact the cost of managing a patient with this intermediate-risk low-grade Non-muscle Invasive Bladder Cancer?
Yeah. Well, the cost is not just for the patient, but it's also for the family members that have to drive the patient to the operating room, and then pick them up. They have to take a day off of work, and then the patient comes home. They may or may not have a catheter. The family member is, you know, keeping track of the patient, making sure they're doing all right. It's, you know, again, when we look at the larger healthcare costs and the morbidity of surgery, it is significant. It is a significant quality of life issue, not just for the patient, but also for their family members and caregivers.
Patient comes in, even 80-year-old patients can drive themselves to the office and get their drug and go home. I think that when you look at the grander scheme of things and then also there's morbidity from surgery. I mean, you know, anytime there's complications, urinary tract infection, urinary retention, blood in the urine and so forth, all of those things add up and make it a very expensive even though it's a relatively what we call a minor operation, but it's only minor when it occurs on somebody else, not when it happens on you or a family member. Anyway.
All right. No, thanks for taking the questions.
Thanks for the questions, Matt. Our next question comes from Mitchell Kapoor from H.C. Wainwright & Co. Please go ahead, Mitchell.
Hey, everyone. Thanks for taking the questions. I just wanted to ask how intensive would training need to be with UGN-102 relative to JELMYTO? What lessons have been learned from the JELMYTO real-world experience that could be applicable to the deployment of UGN-102?
Great question. Bill's got practical experience with both. Bill, you wanna take that?
I think the UGN-102 is significantly easier to deliver than JELMYTO. I think one of the issues with JELMYTO initially was how to best instill it, and I think ultimately the decision to place an ostomy tube as the easiest way of instilling it is probably the best way for patients with upper tract disease. For patients with bladder cancer, it's simply the insertion of a Foley catheter and then installation of the drug, which is what all urology practices, quite frankly, are very familiar with and very comfortable with because we already give BCG and intravesical chemotherapy through this route. It doesn't even really require the physician to be there for the installation.
At least in our practice, this is all done by nursing, and they're in and out within 20-30 minutes.
Great. Thank you. Yep.
You know, I think the concept, you know, you've got to keep it cool until you instill it. Then when it hits body temperature, it becomes a gel. Again, urologists and their practices are early adopters of new technology. I think that UroGen has done a nice job to help facilitate the logistics. Once you've done it two or three times, I think it just becomes rote. As Dr. Hwang pointed out, that urology nurses are capable and do this quite readily.
Great. Thank you so much. In the ENVISION trial, are there any notable changes occurring in how physicians are administering the drug? Are there any kind of tweaks to the procedure, that you could talk about?
I'll comment from a protocol perspective, and then Bill, you may want to comment as an investigator. The answer is no. Bill, I don't know, do you wanna comment on your experience?
Yeah, I would say that the tweaks would be extremely minor, and I think that as we look at how the drug is given now in ENVISION versus how it was originally in the phase IIb trial, there are some slight changes to the catheters. There are some changes to the locking mechanism by which how the drug is delivered, as well as the syringes. These are all minor changes, and if anything, it's made it easier than it was initially, when our experience of delivering this wasn't, you know, quite up to speed as the way it is now. I would say that there really hasn't been any significant changes, and if anything, better than it was initially.
Okay, great. Thank you very much.
Thanks for the questions, Mitchell. Our next question comes from Roderick Ma from Goldman Sachs. Please go ahead, Roderick.
Hi. Just a couple from us. One is, what will be the timing for the home instillation trial to read out? Maybe for KOLs, what's your view for them to instill by themselves at home? Maybe, like, what's your view on the insurance coverage? Thanks.
Why don't we do Gary and then Bill talk about what home instillation might mean for patients first out of that tripartite question.
Yeah. You know, it's interesting that there are a number of companies in the Non-muscle Invasive Bladder Cancer space that are looking at or inquiring about home installation. I'm not quite sure that we're ready for that. Certainly an intravesical treatment at home, again, you would require somebody to catheterize themselves or a family member or a nurse. I think there are rules and regulations on handling chemotherapeutic drugs. I would suspect that it would require a specialty level nurse to do this with specific special training. I'm certain that that can happen in the future. I'm just not sure that we're ready for that right now.
Bill, what are your thoughts about the availability of home installation?
I think it's hypothetically feasible, but as Gary said, there's a lot of hurdles right now that would have to be overcome, including having to catheterize and then proper handling of a drug and a medication, which is essentially a chemotherapeutic agent. When you look at the ability to give these drugs, a lot of these drugs can't even be given outside of a specific setting with training with mixing, et cetera. Although hypothetically feasible, I don't think we're close to that point yet.
Yeah. Thanks. In terms of the answer to when data will be released regarding the home installation study that's ongoing, we anticipate those data would be available, probably first half of 2023. With respect to the physicians' impressions of reimbursement, I assume that's a general question about reimbursement, not just the home installation. Is that right, Roderick?
Yes, that's right.
I don't know. Bill and then Gary, do you wanna talk about your thoughts or, you know, projections as to how insurance might view the use of UGN-102 in the treatment of this patient population?
I think obviously once it is approved by the FDA, that the reimbursement would be very similar to the way that JELMYTO is reimbursed or the way that other intravesical agents are currently being reimbursed right now.
I think that, with FDA approval, I don't foresee significant barrier to getting insurance approval, but that's my personal opinion. I don't know if Gary can provide any feedback on that.
Yeah. I mean, this is a complicated area of CMS and reimbursement and pro fees and so forth. I think, again, as a healthcare system is rapidly evolving to an employee-employer system. How much the physician gets credited for or paid for intravesical installation, I don't really think is all that important anymore as the healthcare system evolves. It will really be based on what the healthcare system collects and their facility fees and so forth. Will you try to get a new code, a CPT code or a J code?
All of those things are very, very complicated because as we know, at CMS, if you give a new code or an increased CPT for one procedure, that means you've got to take it away from some other procedure, whether in urology or in some other field. It is a complicated picture, but I suspect that there will be no financial disincentive for urologists. I think actually there'll be incentive for urologists to incorporate this because it'll free up their time, and they won't be spending time sitting around an operating room waiting for cases to get started and so forth.
Thank you.
Thank you so much.
Thanks for the questions, Roderick. I'll now turn it over to Brendan Payne from LifeSci Advisors to read the webcast questions.
Perfect. Thank you very much. The first question we have is that you, and this is for the broader group. You mentioned the overlap between the prescriber base for JELMYTO and UGN-102. Can you discuss how you intend to leverage your current commercial organization and whether you intend to grow it for UGN-102 launch?
Yeah, sure. Hi, it's Liz. I'll answer that question. We intend to utilize the same commercial organization for both. The likelihood is we will expand it slightly, mostly just really for geographic purposes, 'cause you think about it today, we've got 48 territories around the country. As we expand and have two products on the market, we will likely add a few reps here and there. We'll continue to have our reimbursement managers and continue to have our nurse educators. Our nurse educators have really become a great resource for physicians, and so likely we'll expand those. We're really talking about sort of small expansion and not, you know, not significant. You know, that's what the current plan is.
We will go into a formal analysis around the physicians and who we'll be covering and, you know, to answer that question, but the likelihood is it would just be a few people here and there.
Perfect. Thank you. The next question submitted was, would you expect insurance to require UGN-102 therapy in appropriate patients before reimbursing surgery?
No, we would not expect that. We haven't seen that with JELMYTO. You know, these patients are losing their kidneys, so I don't suspect that you would see that with TURBT.
Okay, perfect. The final question I have is, given that clinical guidelines vary, if demonstrating significant decreasing or reducing likelihood of recurrence, do you think this could be part of a standard first line of care post-TURBT for all grades of bladder cancer, even before first recurrence?
I mean, I'll give you my comment on that, and I'll turn it over to Mark and, you know, Dr. Steinberg and Dr. Hwang to answer the question. I think from a guideline perspective, you would not see them, you know, taking the study and expanding that to all patients. I think we would likely see it as an alternative and an option for physicians to choose. Mark, I'll let you guys give your perspective.
Yeah. Let me ask Gary and Bill to comment first because I have a follow-up question on this. Gary, you wanna take that?
Well, the AUA and the Society of Urologic Oncology, they frequently update their guidelines on non-muscle-invasive bladder cancer. I could foresee this if it's a positive trial and it gets FDA approved, which I suspect it will, I could foresee that this getting into the guidelines. You know, the guidelines are not a recipe. The guidelines aren't mandated, but they are guidelines. I could see how this would fit very nicely into the guidelines, especially in the intermediate-risk patient population. Any time that you know, the FDA, you know, there is a study and there is the package labeling. Whether urologists start using this for low risk or whether they start using it for high risk will be up to them.
In the guidelines, I suspect that it will state this availability and suggest its utilization in the intermediate risk patient population that was studied.
Bill, what do you think?
Yeah, I think that for the time being, the particular cohort of low-grade intermediate-risk patients, once it's FDA approved, will likely expand the treatment options for these patients. You have to keep in mind that this is a completely novel way of treating bladder tumors, though, because we're not talking about instilling this after you've done the scraping. This is in lieu of doing a scraping. This will become a treatment option for patients who have frequent recurrences and have low-grade recurrences. Now, where you go from there, you know, obviously the sky's the limit if this is a potentially new way of treating bladder tumors.
I foresee it beginning with the particular cohort that this was approved for, and then allowing that to be adopted by the guidelines as a treatment option for those with recurrent or intermediate-risk low-grade, and then potentially expanding as time goes on, given a novel way of treating these bladder tumors.
I have a quick follow-up question for both of you. I know we're running out of time, and Liz has some closing remarks. In light of this question, what role do you think patient interest and desire to use this type of a therapy in lieu of surgery will have in terms of its uptake? Bill, you wanna go first and then Gary?
Yeah. I think when patients are given the option after a cystoscopy in the office, well, once again, you have another bladder tumor, we unfortunately have to take you back to the operating room. If we can offer them an alternative that they don't have to undergo anesthesia, they don't have to have a painful procedure, I foresee a lot of patients re-requesting that particular option.
Gary, you agree?
Yeah, absolutely. Especially when the physician and the patient see the efficacy, I think that they'll be quite pleased. You know, the Bladder Cancer Advocacy Network and the patient advocacy groups are always looking for innovation and new therapies, and they are looking for things that will decrease surgery. They wanna keep their bladders. They would like to eliminate or minimize the number of surgical procedures that they undergo.
Thanks.
Perfect. Well, thank you everyone for the great dialogue. I'll now turn the call back over to Liz for closing remarks.
Thanks. I don't really have much to say. I just wanna take an opportunity to thank both Dr. Hwang and Dr. Steinberg for joining us and Mark, as usual, and all of your great questions. Thanks for joining us, and everybody, have a nice day. Talk to you soon.