UroGen Pharma Ltd.

Good day, and thank you for standing by. And welcome to the Eurogen Pharma Q4 2022 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand has been raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Vincent Perrone, Head of Investor Relations. You may begin.

Thank you, operator. Good morning, everyone, and welcome to Eurogen Pharma's fourth quarter and year-end 2022 financial results and business update conference call. Earlier this morning, we issued a press release providing an overview of our recent corporate highlights and preliminary financial results for the quarter ended December 31, 2022. The press release can be accessed on the investors portion of our website at investors.eurogen.com. Joining me on the call today are Liz Barrett, President and Chief Executive Officer, Dr. Mark Schoenberg, Chief Medical Officer, Jeff Boba, Chief Commercial Officer, and Don Kim, Chief Financial Officer. During today's call, we will be making certain forward-looking statements. These may include statements regarding our ongoing commercialization activities related to gel mito, anticipated seasonality for gel mito in 2023, our ongoing and planned clinical trials, commercial and clinical milestones in the year ahead, the potential of UGN-102 to transform the treatment paradigm as the first nonsurgical treatment for low-grade, intermediate-risk, non-muscle-invasive bladder cancer, market opportunities, potential future commercialization activities for UGN-102, if approved, Data presentations, regulatory filings, future research and development efforts, our corporate goals, our optimism regarding multiple avenues available to us to further strengthen our balance sheet, and 2023 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure document. Your caution not to place undue reliance on these forward-looking statements and your agenda's claims any obligation to update these statements. I will now turn the call over to Liz. Liz?

Thank you, Vincent, and thank you, everyone, for joining us today. Looking back on 2022, I'm proud of our progress and more enthusiastic than ever about the future of URGEN. We returned to growth in Q4, delivering our strongest quarter ever for Gelmido, ending the year with $64.4 million in net product revenues. representing a 34% increase from full year 2021. This bodes well for UGM-102 as we continue to think of gel mito as proof of concept and the gateway for the much larger market of bladder cancer. That belief is substantiated by the incredible momentum we experience in our UGM-102 clinical trial. In just 20 months, we've enrolled over 500 patients between both the ATLAS and the Envision Phase III trials. In fact, we completed enrollment of Envision, our pivotal study for UGM-102, for the treatment of low-grade intermediate-risk non-Muslim-based bladder cancer in less than a year. We firmly believe that this has the potential to transform the way urologists treat patients, and based on how quickly we enrolled the trial, that we have a base of urologists who are eager to elevate their practice. We are planning to provide top-line data from both of our phase three studies of UGM-102 mid-year. We will provide an update on complete response and durability in ATLAS while also providing the primary endpoint of complete response rate in the Envision study. Assuming positive results, these studies will form the basis of our FDA submission in 2024 once durability has matured. UGM-102 is designed to address a much larger patient population, and administration is much simpler without the need for fluoroscopy. Therefore, if approved, we anticipate UGM-102 will prove to be our main growth driver in the future. At the end of last year, we shared long-term follow-up data from the Jelmito Olympus Pivotal Trial and the Phase IIb Optima II study of UGM-102. In each of these, we observed a greater than two-year median duration of response. Along with a recently completed small home installation study, we are optimistic about the upcoming data from Atlas and Envision, will further establish the potentially transformative nature of our products. Before turning the call over to my colleagues, I would like to quickly address our balance sheet. We've now come to better understand the adoption curve of Jalmaito and expect revenue growth in 2023 to reflect growth of 20 to 30% over 2022 and revenues of 76 to $86 million. While we ended the year strong with $100 million in cash, We continue to reduce cash spend and focus on our core assets. Especially given the market potential for UGM 102, we're optimistic that we will be in a position to explore multiple avenues to further strengthen our balance sheet when necessary. Overall, I am very enthusiastic about the progress we've made in 2022 and the road ahead as we plan for an FDA submission of UGM 102 in 2024. We believe Gelmito and UGN 102 together represent a billion-dollar revenue opportunity for URGEN and remain focused on solid execution to turn that belief into a reality. With that, I'll pass the call over to Mark to further update you on our clinical development program. Mark?

Thank you, Liz, and welcome, everyone. My comments will underscore Liz's remarks and reinforce our excitement as we advance our lead pipeline program, UGN 102, and highlight recent real-world data from Gelmito. As you may recall, we commenced the International Multi-Center Registrational and Vision Study for UGN-102 in January of 2022. The study is intended to evaluate the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with recurrent low-grade intermediate risk non-muscle invasive bladder cancer. As Liz noted, we expect to report out this data by the end of this summer. The quickness with which we were able to complete this trial is a testimony to the interest from urologists for a new alternative for treating bladder cancer. Our confidence in the potential outcome of InVision stems from its similarity to the Phase II Optima II trial of UGN-102, which demonstrated a 65% CR rate and duration of response at 12 months of 72.5% using Kaplan-Meier analysis. UGN-102 also has key similarities with gel mito. Both products utilize mitomycin, allow for local delivery, and sustained exposure to mitomycin for up to six hours. And importantly, both low-grade NMIBC and low-grade UTUC share many biological and clinical similarities, which leads to common clinical features, including the responsiveness to chemotherapy. UGN-102, however, has many important advantages over gel mito, which we believe will have a direct impact on its use. It does not require special equipment for procedures and is designed to be instilled into the bladder via urethral catheter in an outpatient setting, a common and routine procedure in most urology practices. This advantage will be critical as low-grade intermediate risk NMIBC is 8 to 10 times more common in a condition that is routinely managed by 80 to 90% of urologists. inferring a significantly larger addressable patient population. We recently shared results from a small study that demonstrated the suitability of UGN-102 installation at home by a visiting nurse under the supervision of a treating physician. Six of eight, or 75%, of patients who received six weekly doses of UGN-102 achieved a complete response, defined as no detectable disease after three months of starting treatment. Treatment-related adverse events were mild to moderate, and the few serious adverse events were not treatment-related. We anticipate a small subset of older patients with social challenges may benefit from being treated at home versus in clinic, and the results from this study provide us with added confidence that our novel investigational therapeutic has the potential to address genuine unmet needs for low-grade bladder cancer patients. In December, we shared new and supportive long-term follow-up data from the Optima 2 study of UGN102 at the annual Society of Urologic Oncology meeting. The study showed a greater than 24-month median duration of response with UGN102 in 15 of 25 invaluable patients. Long-term follow-up data from Gelmito's pivotal trial were also presented at SUO. The study showed a greater than 28-month median duration of response in 16 of 23 evaluable patients. Together, these studies added to the growing body of evidence supporting the potential for long-term recurrence-free survival associated with RT-gel delivery of mitomycin to the bladder and urinary tract to treat low-grade urothelial cancer. 2023 is shaping up to be an important year for UGN102 with multiple near-term catalysts, including top-line data from the ATLAS trial, the precursor to Envision, which enrolled 282 patients who completed treatment with either UGN-102 or primary TURBT, top-line results from the Phase III Envision trial mid-year, and assuming positive results from the Phase III trial, preparing for an NDA submission with the FDA in 2024. The goal would be to target priority review, which, if granted, may potentially result in approval at the end of 2024 or early 2025. If approved, UGN-102 will be the only primary non-surgical therapy addressing the nearly 80,000 new patients in the U.S. alone who will undergo repetitive endoscopic resection and are burdened with the risks of surgery and anesthesia as their only recourse for disease control. As a practicing neurologist who cares for bladder cancer patients, This would be a transformative therapeutic advance that I believe will be welcomed by my colleagues and patients alike. Meanwhile, our Phase I trial of UGN301, our in-licensed anti-CTLA-4 antibody for intravesicle administration using RT-GL technology, continues to enroll. UGN301 is in development for use in combination with other immunomodulators, including UGN201, our proprietary TLR7 agonist, and other potential chemotherapy and immunotherapies to treat high-grade non-muscle nasobladder cancer. This study is aimed at identifying the suitable dose for a subsequent Phase II trial. The first arm of this study, evaluating dose ranges of UGM301 as monotherapy, is expected to be completed in the second half of 2023. We view UGM301 as a cornerstone checkpoint inhibitor for a variety of potential combination therapies targeting high-grade NMIBC. In closing, 2023 will be an important year as we look to build upon the foundation of real-world evidence and clinical data supporting our increasingly compelling and well-established technology and product portfolio of innovative non-surgical therapies for urothelial cancers. And with that, I'll hand the call over to Jeff to provide a commercial update.

Thank you, Mark. Q4 represented our strongest quarter performance ever for gel mito. I'd like to take a moment to highlight a few of the underlying factors which contributed to our performance in the fourth quarter. Adoption metrics continue to demonstrate encouraging trends in new and repeat accounts, indicating clinical conviction from gel mito adopters and growth in new users. Activated sites on March 1st, 2023 were 983 compared to 930 on November 1st of last year. And repeat accounts were 214 compared to 177 for the same period. This is a 21% increase over the last period. Reimbursement remains at approximately 99% across all coverage types. In Q4, we saw strengthening of the Joe Mito ramp and an increase in uptake in several key territories. This was driven in part by strategic adjustments to our sales strategy discussed last quarter. including the addition of operation support to facilitate logistical efficiencies and alignment of our field sales team with the appropriate drug and device skill set. We expect the benefits of our revised strategy to deliver sustainable growth in developing territories and are encouraged by the impact seen thus far. Our performance in Q4 also reflects operational efficiencies from the September 2022 label update which extended the stability period of gel mito admixture from 8 to 96 hours. We've seen an immediate positive impact to several logistical challenges, including allowing for delivery of the admixture the day before installation, enabling HCP preferred or early morning installation. This has led to a shift of approximately 50% of doses to day prior delivery, facilitating expansion of the geographical coverage of our mixing partners and optimizing our territory business managers' time in the field. The growing body of outcomes from real-world evidence data continues to reinforce Gelmito's efficacy and safety. In addition to supporting a multimodal approach of Gelmito across multiple use cases, the recent independent multicenter retrospective analysis has answered a number of questions not addressed by Olympus. Arming our commercial organization with a deeper understanding of Gelmito's use across various practice patterns. Further, outcomes from this study adds to the growing body of real-world data demonstrating a favorable safety profile and additional benefits of integrated administration, which now represents approximately 60% of Gelmido installations. After two years of market experience with Gelmido, we expect to see stability going forward with respect to quarterly variability or seasonal dynamics. as we get back to a new sense of normal. Looking ahead, we expect typical payer dynamics in play in Q1 resulting from deductible resets, followed by stronger demand in the second quarter, slight delay in Q3 as we expect PEP conversions to slow in the summer months, followed by a stronger Q4 as PEP conversions return to baseline. Gelmito is undeniably gaining traction, and adoption appears to be accelerating as the product becomes increasingly proven, easier to administer, and incorporated across multiple practice patterns. This reinforces our optimism and lays the foundation for the potentially much larger opportunity with UGN102 in low-grade, intermediate-risk, non-muscle-invasive blast bladder cancer. With 95% overlap in the prescriber base and well-established practice patterns, we expect a seamless integration of UGN-102 into our commercial efforts, if approved. With that, I will turn the call over to Don to discuss our financial results. Don?

Thank you, Jeff, and thank you to everyone for joining today's call. We finished the year with growing momentum, delivering our strongest quarter ever for Jelmito Net Sales. On an annualized basis, revenue from Jeremiah 2 sales grew 34% in 2022. For the fourth quarter of 2022, we reported Jeremiah 2 net revenues of $18.1 million compared to $16.1 million for the same period in 2021. On a full year basis, we delivered Jeremiah 2 net revenues in line with consensus estimates of $64.4 million compared to $48 million for the year Our performance reflects a strengthening ramp and growing adoption of gel mitre. For the fourth quarter of 2022, research and development expenses were $14.4 million as compared to $13.1 million for the prior year quarter. R&D expenses were $52.9 million as compared to $47.6 million for the full year 2021. The increase in R&D expenses of $5.3 million is primarily attributable to higher research and development expenses in 2022 related to Phase III InVision study for UGN-102, research into ingredient scale-up, and production efficiency for Jelmito, partially offset by lower stock-based compensation expenses in 2022. For the quarter of 2022, selling, general, and administrative expenses were $21.6 million as compared to $21.4 million for the prior year quarter. Full year 2022, selling, General and administrative expenses were $82.9 million as compared to $87.5 million for the full year 2021. The decrease in SG&A related expenses of $4.6 million resulted primarily from a decrease in stock-based compensation and compensation related costs in 2022 offset by brand marketing related expenses. For the fourth quarter of 2022, we reported financing expenses related to the prepaid forward obligation to RTW investments of $5.1 million. Financing expense related to the prepaid forward obligation to RTW investments totaled $21.6 million for the full year 2022. The cash payout rate for 2023 will be 13% based on $64.4 million of global net product sales of J-MITO in 2022. We anticipate full year 2023 J-MITO net revenues to be in the range of $76 to $86 million. Full-year operating expense is expected to be in the range of $135 to $145 million, including non-cash share-based compensation expense of $6 to $11 million, subject to market conditions. We will continue to scrutinize all expenses in support of our efforts to prioritize cash preservation. Financing expense related to the prepaid or obligation to RTW investment is expected to be in the range of $21 to $26 million, of which approximately $9.8 to $11.1 million will be paid in cash. In addition to RTW financing expense, interest-only payments on the $100 million term loan facility with funds managed by Pharmacon advisors will be made quarterly and continue to accrue at a rate of LIBOR plus 8.25% in 2023. We ended the year with $100 million in cash and cash equivalent, which is expected to finance operations into the first half of 2024. To echo Liz, we are committed to diligently and proactively managing our balance sheet in support of our commercial and clinical development activities. We will continue to watch revenues and monitor expenses closely while also routinely evaluating our cash position and capital market environment to the needs to opportunistically strengthen our balance sheet arise. With that, I'd like to turn the call back to Lee for closing remarks.

Thank you, Don. I'd simply like to close by expressing my pride in all that we have accomplished and continue to execute on from the leadership right through to the entire URGEN team. I'd also like to express my sincere thanks to those individuals, as well as to the patients and clinicians that are realizing the benefits of gelmito adoption and the diligence of the investigators and patients participating in our ongoing clinical trial. Finally, I'd like to thank and reiterate our commitment to our shareholders who see the importance of the goal that we are trying to achieve. We look forward to keeping you all apprised as important events continue to unfold over the weeks and months ahead. I'll now turn the call over to the operator for a Q&A session. Operator?

And thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. And one moment for our first question. And our first question comes from Leland Gershel from Oppenheimer. Your line is now open.

Hey, good morning, guys. Thanks for taking the questions and congrats on the progress. Two questions for me. First for Mark, you know, as we'll wait for the durability data from Envision, obviously early next year after we get the response top line. And any reasons we should think that would differ than what we saw from what we saw in Optima 2? And then second question for Liz, just teeing off the comments you made about the size of the UGN-102 market opportunity providing potential opportunities to strengthen the balance sheet, just wondering if that should lead us to think about any sort of visit development or strategic arrangements you may be contemplating down the road with UGN-102 as you get to commercial. Thanks.

Okay. Thanks, Leland. Mark, why don't you answer and then I'll come back.

Sure. Thanks, Leland. Good morning. So the short answer is no. Just to remind the listeners, in Optima, about 25% of the cohort studied were patients with de novo disease. The remainder are those patients who had recurrent disease. In Envision, all patients will have had recurrent disease. When we evaluated this question as to whether or not there was a difference between new and recurrent responses to UGM-102 in the Optima cohort, we were not able to discern a difference. based on that cohort. So our expectation is that in the Envision trial, we will see very similar results to what we reported in Optima.

And, you know, to answer your question, Leland, I mean, to be honest with you, we're looking, you know, we're always opportunistically looking at everything. So whether it be BD, a strategic partnership, you know, other forms of capital. So we just want to make sure that, you know, we keep doing the diligence around our expenses. And we have further identified areas where we can really reduce expenses to make sure our cash keeps us through 23 and into 24 so that we're not forced to do anything. But look, it would be great to be able to do some sort of strategic partnership with a company if we thought it was the right thing. And if we thought it was really going to accelerate you know, our growth. And so, you know, we'll continue to look at that as well as, you know, a lot of other options as well. But nothing has been decided. We haven't, you know, we just feel like, you know, given that the data is coming up, you know, this summer, that that's probably a good time to think about doing something. So, thanks for the question.

Great. Thanks for the .

And thank you. And one moment for our next question. And our next question comes from Mitchell Kapoor from HCW. Your line is now open.

Hi, everyone. This is Mitchell on for ROM. Thanks for taking our questions. The first one is I just wanted to ask about the main driver of gelmito uptake now and how that's differed since the original launch. And how does the company intend to optimize the value of XUS?

Jeff, you want to take that, and then I'll take the XUS question.

Sure. So, hi, Mitchell. The main driver continues to be, you know, patient identification, getting into the offices and really, you know, sitting down and looking at various codes that help identify patients that could benefit from gel mito. The data continues to get better. We continue to do that. And then physicians, as you saw from the number that increased from repeat users, they also, once they get experience, they also look for other patients in the practice. We obviously have this data will be out there in the hands of the field. So, prior to, you know, Q4 that we just reported, this data wasn't available. So, we're certainly excited about the pieces of data, the long-term follow-up, the Waldue, which is the retrospective, as well as the ROSE paper, which talks about additional antigrade installation. to continue to help us get in. New data is always a positive. It allows access. Physicians are going to be very and have been very interested in hearing about the new data, since the real world evidence is really how they're using gel mito, which, as you can see, is oftentimes endoscopic resection, getting what they can see, understanding that there's microscopic disease that they couldn't see, and coming back with six doses of gel mito.

And on the XUS question, I think, you know, as we've talked about before, you know, the challenge with XUS isn't getting an approval on the data we have today. It's really getting reimbursement. So for, you know, a market like Europe, you know, for us to get reimbursement at a decent rate that's, you know, that's viable for us or a partner to go in there, we really need to do another study. And so because we've prioritized the work that we're doing here in the U.S. for obvious reasons, So, we see that down the road, but we absolutely see an opportunity, you know, to do more clinical work that would get us, you know, global, you know, give patients, frankly, global access. And right now, we do have a named patient program. We actually have had a lot of success with a few patients, you know, that have had good results after using it through the named patient program, because one piece of actually getting governments to pay is when physicians start asking for it. So with a named patient program and them getting some experience with that and, you know, their ability to be able to get access to it. So right now we're really focused on the U.S. and making sure we're bringing you 102. But, you know, we know what it would take to, you know, to do something. And it would require another study outside the U.S.

Okay, great. And then Yeah, and on 102, just wanted to ask if the commercial strategy will require any additional infrastructure in the U.S.

Yeah, Jeff, do you want to just talk about sort of our thoughts around that?

Sure. Well, because there's a 95% overlap in key targets, it will not require a significant resource expansion. We'll always take a look at larger geographies, you know, to cut down on windshield time. But because the overlap is so significant, I don't see a reason for a larger major expansion with the hopeful approval of 102. Okay, great.

Thank you all.

And thank you. And one moment for our next question. And our next question comes from Paul Choi from Goldman Sachs. Your line is now open.

Hi, this is Roderick for Paltroy. Thanks for taking our questions. So the first question is, what could drive further adoption of Gemalto in 2023 and maybe potentially reach the higher end of your guidance? And maybe another question is, in 2023, do you anticipate to report additional real-world data, including maybe the physician's feedback based on the stability change in the label? in this year?

Thanks.

Jeff? Sure. I think the three pieces of data, actually four, are going to drive greater adoption in 2023. I'll start with the operational data that we have. The FDA approved an eight to 96-hour stability period. That's already resulted in 50% of doses being delivered a day prior. So we've been able to re-engage physicians that may have been a little reluctant to adopt gel mito because of the eight-hour restriction. The second is certainly the question on long-term follow-up. How long do patients stay disease-free? And we've been able to, you know, from the Olympus data, follow a number of those patients where we see the median at 29 months. Although the number is, you know, follow-up is a little bit smaller, that's very significant when physicians question or wonder, you know, well, you know, Olympus gave us 12 months upon approval, but now we see long-term follow-up with a median of 29 months. I think more importantly, the two pieces, the real-world evidence, talks about how physicians really practice. that's going to be key and to go in and be a partner with multimodal, what we use, we use the term multimodal, be a partner with endoscopic resection. And so for those physicians that may have only been resecting and holding off on using gel mito, you'll be able to go in and talk about the difference in CR. When I say that you, the representatives will be able to get in and talk about the difference in CR, the increase in CR. And then finally, the Dr. Rose paper with 32 patients, showing only a 9% stenosis rate with antegrade administration versus the 44% that we saw in Olympus. So all of those key pieces of data give me confidence that we're going to see growth in 2023 from that.

I think what, Liz, I'll just add one more comment around the 96 hours. The other thing that 96 hours does for us is it actually frees up our reps. Because in a lot of cases, you know, when you only had eight hours, the rep had to make sure that the dose got to the doctor's office on time or the hospital or wherever it was going. And now that we have more time, they don't have to worry about that. And so that's actually very helpful. So they can spend their time actually out generating more patients and generating demand, you know, versus really babysitting the dose to make sure it gets to the doctor's office. But thanks for the question.

Thank you. And thank you. And one moment for our next question. And our next question comes from Boris Beaker from TD Cowan. Your line is now open.

Great, thanks. This is Nick on for Boris. I just have a quick question or a quick two questions on the Atlas trial. Will you be releasing the TURBT patient data from ATLAS? I know that you're planning to release about 280 patients' worth of data. Does that include TURBT? And then also from the UGN-102 arm of the ATLAS trial, will this will allow for a potential read-through to the Envision trial?

Mark, do you want to give your perspective and then I'll add any commentary?

Sure. Sure. Thanks for the question. The answer is that we will be releasing the data from the TUR arm as well. I would caution everybody to remember that because the study is underpowered, we will not be able to compare the arms. However, it will give us a sense in this cohort of the performance of surgery and probably as, or more importantly, safety issues around surgery in this population, which is an area of some interest and study in our community right now. And then secondarily, In the 102 arm, I think we have said on multiple occasions we will be providing complete response and durability data as well as safety data for that group of patients. And with the caveat, again, about not being able to compare arms, we do believe that given the substantial comparability of this population to the optimal population reported in our Phase II experience, we believe that it will be supportive and directionally in line with what we've previously reported and what we would expect to see in the Envision cohort as well.

Yeah, so I'll just add two caveats, right? Our Optima 2 study was only 65 patients. Typically, if you look at clinical studies, and, look, I haven't seen the data, so I have no idea, you typically see, you know, somewhat of a decline, right, in efficacy because you have a much bigger patient population. So we'll see. But we believe, to Mark's point, that it will be, you know, that will definitely, you know, be aligned in that case. The other thing is I just also want to caution everybody on the data that we will share, because we will share top-line data, but we will not share all of the data, mainly just because we want to get a publication, a peer-reviewed journal, and we want to present it at a meeting, and you know that if we give all of the data, then that won't happen. You know, we will give top-line data. We won't go into all of the details, but we will get that out, you know, in a paper and a presentation as quickly as possible. So, thank you for the questions.

Yeah, thank you very much. Just on UGN-102, the at-home administration, do you plan to run an additional trial for this? Or, like, is this more so going to be just for physicians to see and potentially then use if they need to?

Yeah, we're not planning to run another study. I think from our perspective, there were a couple of things, right? We were in the middle of COVID when we, and actually it was our chairman, Ari, that suggested it. You are hearing a lot more around, frankly, you know, home is a hospital, I think is a coined phrase that we've heard. you know, bringing it home. And, you know, we think that there'll be an opportunity in the future. But reality of it is, is that most patients, and we even saw that even in that study, most patients want to go into the doctor's office. And so, but we do think, you know, maybe in nursing homes and there's opportunities. So I think we'll see what the demand is for it once 102 is approved. And, you know, absolutely, we could support, you know, an investigator-initiated study, you know, a bigger, bigger study. But The likelihood of us doing a large study to go after an approval, I would say probably not very likely. But I think the data will allow. I mean, there's not going to be anything in our label that wouldn't allow for, you know, home delivery through a nurse, a home health nurse, just like they get other things through home health today. So I'm not sure that we need a study to be able to do that.

Great. Thank you very much.

Thank you.

And thank you. And one moment for our next question. And our next question comes from Matt Kaplan from Lattenburg, Thalman. Your line is now open.

Hi, good morning, and thanks for taking the question. Just to, I want to dig in a little bit more to Joe Mito and your revenue guidance and specifically potentially returning to more accelerated growth of Joe Mito. Can you talk a little bit about the current use and adoption of the Melchizedek in terms of administration of Salmido, and what are your thoughts kind of going forward in terms of that helping to drive growth further?

Jeff?

Sure. Hey, and hi, Matt. Thank you for the question. It continues to go up. You listen every quarter. It goes up a certain percentage, you know, 5% or 10%. I think with the Dr. Rose paper, you're going to see a bump in physicians that maybe have been a little reluctant. If they just really wanted more data, now 32 patients, you have a similar, if not better, CR. And then you have, most importantly, is a reduction in stenosis. I don't ever, I can say for a fact, it will never be 100% of the installations. Sometimes patients don't really want don't want the catheter in their back for six weeks. So there are always going to be a subset of retrograde installations. But I do see it continuing in the next few quarters because of the ROSE data, you know, 5% or 10% every quarter, and the convenience to patients. As physicians experience being able to give this in the clinic, what we see is usually their first attempt at antigrade leads to future attempts at antigrade. So as they identify patients, they no longer give it in a retrograde fashion. They've moved their administration to strictly antigrade.

And then a follow-up with respect to the impact on the stability period. When do you think you'll, obviously it's early in the label change, but when do you think you'll see kind of a full impact on on improving adoption .

I think Q2, we've already seen it go from 20% to 50% in a short period of time of day before installations. I think you're going to see that continue to increase. Look, some physicians still don't need it the day before, just depending on when they want to do the procedure. But I think what it does is if 50% are the day before, it's freeing up, as Liz alluded to earlier, that time of the representative. And so you'll start to see more demand-driven activities from the representative versus really ensuring that operationally the dose arrives. So as our independent pharmacies and our partner pharmacies, the mixer that we currently use, you know, adopt and get used to mixing later in the day and delivering it later, that'll continue to become more efficient. And we'll follow the guidance of the practice. If they were required the day before, we'll continue to evolve there. So, you know, Q2, Q3 would be the impact and then from then on forward. In the end, it frees up more time for the representative and as we deliver the dose the day before.

Oh, sorry, Matt. I was just going to comment to your question around the growth. I mean, I think what we have said and I think what we continue to see is slow, steady growth. So unlike, you know, will there be a time where you'll see a hockey stick inflection point? We don't think so. We think that it will continue to grow. We're seeing that. We're seeing more stability, more consistency, and you'll continue to see that. And I think that is reflected in our guidance for the year. But We're happy about that. It's good to see that consistent growth. But we don't think that even given the great data that we have, we think we'll continue to get more and more physicians. And we've been adding physicians every quarter. We add physicians, new physicians. And it does get back to what Jeff said earlier around finding the patients. Again, there's 6,000 to 7,000 of these patients being treated. by 10,000 physicians. So it's always a matter of being in the doctor's office at the time that they identify that patient. But thanks for your question. I hope that helps.

No, that's helpful. And then just a question on 102. Given the expectation for top line data in the middle of this year, 2023, can you elaborate more on the regulatory timeline for the product and And the rate lending staff, whether it's CMC or long-term follow-up, what's the rate lending staff going to do?

Yeah, it really is durability, waiting for durability. The agency was very clear, and we've talked about that as well, that durability is very important. So even though complete response is our primary endpoint, a key secondary endpoint is durability. And the FDA wants to see some strong durability data. So we have to wait until, you know, remember, you know, we look at CR after three months from the time they started therapy. And then we need all of those patients to have a minimum of 12 months. The good news is obviously some of them will have more than that. And that was the strategy we used with Jalmido is we didn't wait for everybody to have a long-term follow-up, but we were able to go in there with the majority of them For 102, we'll wait for everybody to have 12 months, you know, post their CR, and that will give us some strong data in which to go forward to the FDA. So that's really what's driving the timing. CMC, knock on wood, in this case, because it is so similar to Delmito. We don't really foresee any issues there. We think that will go very smoothly. It really is just a matter of the clinical data and getting the database cleaned once we get the durability and having that data to go forward. We haven't given a time exactly of when we're going to file. It is also an event-driven study. In addition, we have to know we have a certain number of events as well. That's what will drive it. We're comfortable saying 2024, and we're, you know, we're comfortable saying that, you know, if given priority review, you know, we could, you know, could potentially get at the end of 24 or, you know, beginning of 25.

So durability data first half of 24, is that the expectation?

Well, yes, exactly. Absolutely. Okay.

Yep. Thank you. And then, and last question in terms of 301. What will you be looking for on the data 301 when that report's out later this year?

Yeah, Mark, you want to talk about 301?

Yeah, sure. Thanks, Matt. So what we're currently doing is dose escalating 301, and that obviously is predominantly a safety experience for the appropriate dose. So the initial finding is going to be the appropriate dose. Subsequently, our plan, as I think you know and others do, is to combine this with other immunomodulators and chemotherapeutics. So ultimately, though those data will not be forthcoming this year, hopefully in the near term, we'll be able to share combination data that would provide evidence of efficacy in this high-grade population, which is obviously different than the gel mito and UGN-102 populations we've been focusing on. But for right now, what we're focusing on is finding the appropriate dose and demonstrating safety.

All right. Thanks a lot, guys.

And thank you. And one moment for our next question. And our next question comes from A.J. Velazquez, male, from Jefferies. Your line is now open.

Hi, y'all. This is A.J. for Chris Harrison. Just one additional question here. For the Envision trial, what gives you confidence that a single-arm design is sufficient for approval? And would you consider or could you get like a SPA agreement with the FDA?

So, Mark, do you want to talk about the feedback we got from the FDA? And I can also add any color.

Yeah, thanks. Thank you. The confidence has to do with our interactions with the FDA in presenting our Phase II data and long conversations with them about the role we believe UGN-102 can play in neurologic practice. So on the strength of the Phase II data, as well as our interactions with the agency, we believe, and they have provided reassurance in writing, that the design of the ENVISION trial would support approval of UGN 102 and that the decision will be based upon the totality of the data we present to them.

Yeah, I think the only thing I'll add is two things about SPA. I mean, the agency doesn't do SPAs very often any longer, and so we would have had to have done that before. So, no, we don't have a special protocol assessment with the FDA, but we do have our minutes from our meeting that says that a single-arm study can be the basis for an approval. And they've made it very clear, and we've shared this before, that we'll go to an ODAC And frankly, we're very happy to go to an ODAC. We believe we'll win in an ODAC. We know that physicians want access to this medicine, and so we're very comfortable and confident with that. And as Mark mentioned, what they say is it's got to be clinically meaningful, and it's based on the totality of the data, which is not different than what they would expect to say, that we would expect them to say. But the good news is that what everybody has to keep in mind here is there is not another therapy. to compare UGN1022. The only other treatment is surgery. And there has never been, across any therapeutic area, a study that had to be done to get a therapeutic approved where they had to demonstrate how it did versus surgery. It was always looked at as an option to surgery. And so, you know, that was part of the argument, you know, that we had with the, you know, with the FDA and the discussions around it. And, you know, they agreed. And so, you know, and, you know, add that to the complexity of trying to make a comparison, you know, to a surgery. And that's why, you know, ultimately the FDA agreed. They just weren't comfortable. Frankly, we asked for approval on our phase two study. They just weren't comfortable with 65 patients. So they're like, we need a much larger patient population. And we agreed with them on the 220 patients. So I hope that's helped.

Very helpful. Thank you. Very helpful.

Thank you. And thank you. Thank you. And I am showing no further questions. I would now like to turn the call back over to Liz Barrett for closing remarks.

Thank you, Operator. And again, as always, we really appreciate your interest in our company. We're very excited about what's happening with John Mita. We're very excited about the fact that this year we'll actually be able to share data on a significant number of patients for UGN-102, as everybody knows. And that's been a highly anticipated medicine for us. And, you know, we appreciate everything and look forward to sort of sharing more as the year goes on. So let us know if you have any additional questions. Always happy to to jump on the phone. So operator, you can now disconnect. Thanks, everyone.

This concludes today's conference call. Thank you for participating. You may now disconnect.