UroGen Pharma Ltd. Q1 FY2022 Earnings Call

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to UroGen Pharma's First Quarter 2022 Financial Results and Business Update Conference Call. It is now my pleasure to turn the call over to Vincent Perrone, Senior Director of Investor Relations for UroGen Pharma. Please go ahead.

Thank you, operator. Good morning everyone and welcome to UroGen Pharma's first quarter 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 financial results for the quarter ended March 31, 2021. The press release can be accessed on the Investors portion of our website at investors.urogen.com. Joining me on the call today are Liz Barrett, President and Chief Executive Officer; Dr. Mark Schoenberg, Chief Medical Officer; Jeff Bova, 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 relating to Jelmyto, 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 viable nonsurgical alternative for low-grade intermediate risk NMIBC, potential future commercialization activities for UGN-102, if approved, data presentations, regulatory filings, future research and development efforts, our goals, potentially reaching cash flow breakeven by 2025 and 2022 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 documents, including under the risk factors heading of our quarterly report on Form 10-Q for the quarter ended March 31, 2022, filed today. You are cautioned not to place undue reliance on these forward-looking statements, and UroGen disclaims any obligation to update these statements. I will now turn the call over to Liz.

Thank you, Vincent. And thank you everyone joining us today. UroGen remains focused on developing novel therapies for urothelial and specialty cancer, with the goal of fundamentally transforming the treatment paradigm for what we believe is a largely underserved patient population. During the first quarter, we continued to make important progress toward achieving this goal while setting the stage for several meaningful commercial and clinical milestones in the year ahead. Growing patient access and awareness continue to drive adoption of Jelmyto. Total net sales in Q1 were $13.6 million, in line with our expectations and representing an 81% increase over the first quarter of 2021. Jeff will provide more detail on our commercial efforts, and we remain optimistic about our ability to accelerate growth during the remainder of 2022. In March, we held our first-ever in-person national sales meeting. I'm pleased to say it was a great event that gave the commercial organization an opportunity to come together, exchange ideas and best practices, and take actionable learnings into the field with a common goal of ensuring that all appropriate patients have access to Jelmyto. Beyond Jelmyto, we made significant progress in the clinic, advancing our lead development program, UGN-102, and initiating a first-in-human study of UGN-301, expanding our clinical focus to include immunotherapies for the treatment of high-grade disease. Turning first to UGN-102, which aims to address a major unmet need in low-grade intermediate risk non-muscle invasive bladder cancer, an indication impacting about 80,000 patients in the United States each year. During the first quarter, we began dosing patients in our single-arm open-label Phase III ENVISION pivotal trial of UGN-102. We believe ENVISION has a high probability of technological regulatory success, given its streamlined design and encouraging results from the previously completed Phase II OPTIMA II study. We anticipate completing enrollment by the end of 2022 and, assuming positive findings, submitting an NDA for approval in 2024. Importantly, if approved, UGN-102 will share our prescriber base with Jelmyto, allowing for an efficient and expedient product launch within our established commercial organization. We continue to believe that Jelmyto and UGN-102 together represent well over a $1 billion revenue opportunity for UroGen, and the initiation of our Phase III ENVISION pivotal study of UGN-102 moves us closer to realizing the full potential of this innovative investigational therapy. I'm pleased to announce that last month, we initiated a novel multi-arm Phase I clinical trial intended to evaluate the safety and tolerability of UGN-301, as monotherapy and in combination with other chemotherapies and immunomodulators as our first immunotherapy investigational candidate intended to treat patients with high-grade disease, which remains a high unmet need. Mark will provide additional details regarding our Phase I study that represents a unique approach to treating high-grade non-muscle invasive bladder cancer. With the closing of an up to $100 million term loan facility with funds managed by Pharmakon Advisors earlier this year, we took important steps to significantly strengthen our balance sheet. This capital gives us the financial flexibility to continue expanding our commercial and development efforts. Based on our current financial projections, we believe we have the tools needed to reach cash flow breakeven by 2025. At UroGen, our mission is to build and commercialize a strong portfolio of innovative therapies with the potential to meaningfully advance the standard of care in urologic and specialty oncology, moving away from repetitive surgeries and disease management to minimally invasive therapeutic ablation of tumors and locally administered immunotherapy approaches. We expect 2022 to be a pivotal year for our company. As we aim to accelerate growth and create meaningful value for our patients and shareholders, we remain focused on several key deliverables, which we believe are critical to our success this year. We are on track to achieve our guided full year revenue range of $70 million to $80 million in total Jelmyto net sales. We expect to fully enroll our ongoing Phase III ENVISION pivotal trial, bringing us closer to an NDA submission in 2024. With the initiation of our novel multi-arm Phase I clinical trial of UGN-301, our anti-CTLA-4 antibody, we expanded our clinical development focus to include immunotherapies for the treatment of high-grade disease. And perhaps most importantly, we believe we have the tools and sufficient capital to support our business through cash flow breakeven. I'm extremely proud of the progress we continue to make toward our goal of bringing novel solutions to patients that deserve better. With that, I'll turn the call over to Mark to discuss our recent clinical and development update.

Thank you, Liz. As Liz noted, the first quarter was one of meaningful progress in the clinic as we made important advances in both our late- and early-stage development programs. During the first quarter, we announced the initiation of our pivotal Phase III ENVISION clinical trial. As a reminder, ENVISION is designed as a single arm multinational, multicenter study, evaluating the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low-grade intermediate risk non-muscle invasive bladder cancer. ENVISION is expected to enroll approximately 220 patients across 90 clinical sites who will receive six once-weekly intravesical installations of UGN-102. The primary endpoint will evaluate the complete response rate at three months after the first installation and the key secondary endpoint will evaluate durability over time in patients who achieve a complete response at the three-month assessment. We remain very optimistic about the design of the ENVISION trial and the clinical potential of UGN-102 for several reasons. First, ENVISION shares a similar design to our previously completed Phase II B OPTIMA II study which also enrolled patients with recurrent low-grade intermediate risk NMIBC. OPTIMA II showed a complete response rate of 65% and the probability of remaining in complete response at 12 months is 72.5% by Kaplan-Meier analysis. Earlier this year, we began treating patients with the goal of completing enrollment before the end of 2022. I'm pleased to report we remain on track to achieve this milestone, positioning us to submit an NDA for approval in 2024, subject to positive results from the trial. While ENVISION remains our top priority for UGN-102, we also continue to advance the single arm at-home installation feasibility study for UGN-102. We believe establishing a precedent for a convenient at-home solution is a groundbreaking step in facilitating access to care and addressing quality of life issues that many elderly patients face with the current standard of care. A total of ten patients are expected to enroll and complete this study this year. Like Jelmyto for low-grade UTUC, we believe UGN-102 is an innovative advance in patient care that could positively transform the treatment paradigm as the first viable nonsurgical alternative for low-grade intermediate risk NMIBC. I'm also pleased to provide an update on UGN-301, our immunotherapy program in development to treat high-grade disease. UGN-301 is our in-licensed anti-CTLA-4 antibody for intravesical administration via RTGel in development for use as monotherapy and in combination with other immunomodulators and chemotherapies to treat high-grade NMIBC. Earlier this year, we announced FDA clearance of an IND application supporting human clinical trials of UGN-301. I'm pleased to report that at this time, we have commenced our planned Phase I clinical trial of UGN-301. The ongoing Phase I study will evaluate the safety and tolerability of intravesical UGN-301, as monotherapy and in combination with other immunomodulators, including UGN-201, our proprietary TLR7 agonist, as well as other potential chemotherapy and immunotherapies in patients with recurrent NMIBC. This study will also seek to establish the recommended Phase II dose of UGN-301, both as monotherapy and in combination therapy. Importantly, the study will utilize a novel master protocol design that we believe provides for a more efficiently streamlined development program since it affords us the flexibility to evaluate multiple combinations in parallel as the study progresses. We anticipate the first arm of the Phase I study evaluating UGN-301 as monotherapy will take approximately 12 months to complete. We continue to view UGN-301 as a fundamental checkpoint inhibitor and the cornerstone of a variety of potential combination therapies targeting high-grade cancers. Treatment of high-grade NMIBC remains a high unmet need, particularly post-BCG and given current supply limitations. There are few options for these patients, and we believe we have a unique approach with combination therapy that can provide incremental benefit to currently approved and investigational medicines. We believe intravesical administration of immunotherapies utilizing our RTGel technology provides us with a host of new opportunities to evaluate a variety of novel immunomodulatory drug combinations that may advance care across multiple clinical indications in neurology and specialty cancers. As this program advances, we will continue our efforts to identify, evaluate, and prioritize therapies that may be synergistic with our proprietary technology with the goal of advancing care across urothelial and specialty cancers. And with that, I'd like to turn the call over to Jeff to provide a commercial update.

Thank you, Mark. I'm pleased to provide you with an update on our ongoing commercial rollout of Jelmyto. As Liz noted, revenues for the quarter were $13.6 million, down sequentially from our record fourth quarter 2021 sales but much stronger when compared to the same period last year. As discussed during our call, we expected an element of seasonal softness heading into the first quarter, which we attribute to the deductible resets typically seen at the start of the year as well as some stocking that typically happens at year-end. Importantly, in light of our expectations for the remainder of the year, we remain on track to meet full revenue guidance of $70 million to $80 million in total Jelmyto net sales. We attribute this confidence to encouraging trends in patient uptake, activated sites, and repeat prescribers. We also saw an uptick in the number of bulk orders for Jelmyto, which we view as an indicator of a positive treatment experience from the perspective of both physicians and patients. We're optimistic these trends may suggest that we're moving towards a more normal launch environment compared to when we launched Jelmyto in mid-2020. With our field force now primarily interacting with physicians in person, we're getting the high contact engagement with accounts that we previously emphasized as a critical component for Jelmyto's success as a buy-and-bill drug. And while our key metrics continue to suggest growing enthusiasm and adoption for Jelmyto in both new and repeat prescribers, we believe we're well positioned to generate additional momentum in the field by going deeper into the existing accounts to identify new patients while continuing to instill reimbursement confidence. Our field reimbursement team continues to do an excellent job of educating and supporting accounts to facilitate a smooth and seamless reimbursement process. The result of which is greater patient access to Jelmyto across all payer channels and a growing base of successful reimbursements. I'm pleased to report that today our metrics indicate payer coverage of Jelmyto in 100% of Medicare fee-for-service claims, 98% of managed Medicare claims, and 97% of commercial plan claims. During her remarks, Liz mentioned our inaugural in-person national sales meeting, and I'd like to spend a moment sharing some of the key takeaways from that event. The national sales meeting was held in March in New Orleans and represented a very important milestone for UroGen since it was the first time since Jelmyto's launch that every level of our commercial organization was able to come together in person to meet, exchange ideas and best practices, and strengthen connections as a team. At the meeting, we rolled out enhanced messaging and data-driven sales resources based on the feedback from healthcare professionals and from our field team. We expect these new resources to improve our team's ability to effectively engage with new and existing accounts in the field to further drive appropriate adoption and patient penetration. Additionally, we recognized our top territory performers. These top colleagues have demonstrated in their respective accounts that the opportunity does exist once physicians embrace Jelmyto as a standard of care. Our goal is to replicate this across the country, which will result in strong growth and meaningful penetration and adoption. From a medical affairs perspective, we continue to make progress with UTrack, our Jelmyto Registry. During the first quarter, we continued implementing our phased launch of the registry, which is expected to provide insights into the real-world outcomes of UTUC patients treated with Jelmyto and evaluate its use in clinical practice in the U.S. The registry is also designed to accrue data to answer specific questions we received, which were not answered or only partially answered by the OLYMPUS trial and may include use of Jelmyto in ureteral-only tumors, partial responders, and retreatment amongst others. We're particularly interested to learn more about Jelmyto's potential utility as multi-dose adjuvant therapy after endoscopic resection as this was not evaluated in clinical trials. We look forward to sharing additional details at the appropriate time. I'm pleased to report we expanded the pilot named patient program to a total of four international patients who have received Jelmyto on a named patient basis in both Israel and Australia. As we return to normal in-person meetings, we look forward to having a major presence at the key urology conferences, including the American Urological Association, or AUA, which will be held from May 13 through May 16 in New Orleans and is the largest medical conference in the urology space. AUA will be an in-person meeting this year and will allow UroGen to meet with physicians and provide education on Jelmyto and our pipeline programs. We will have both a virtual and in-person booth, including an interactive patient builder and demonstrations on how our innovative hydrogel technology is advancing care in uro-oncology. We'll also have a product theater with Dr. Jennifer Linehan, focused on how Jelmyto is helping to transform the treatment paradigm in low-grade UTUC, moving away from previous surgical treatments to the first drug therapy of its kind. With that, I'd like to turn the call over to Don for a review of the financials.

Thank you, Jeff. And thank you everyone for joining today's call. I'm pleased to be with you today to review our financial results for the first quarter ended March 31, 2022. UroGen recorded net product sales of Jelmyto for the first quarter of 2022 of approximately $13.6 million. This compares to $7.5 million in the first quarter of 2021. Cost of revenues for the first quarter of 2022 was approximately $1.5 million, resulting in a gross margin of 89% compared to a gross margin of 88% in the first quarter of 2021. Research and development expenses for the first quarter ended March 31, 2022, were $12.7 million compared to $10.5 million for the same period in 2021. R&D expenses included $726,000 and $1.1 million in noncash share-based compensation expense for the first quarter of 2022 and 2021, respectively. The increase in R&D expense in 2022 is related to the ongoing Phase III ENVISION study of UGN-102, which was initiated in the first quarter of 2022. Selling, general and administrative expenses for the first quarter ended March 31, 2022, were $21.3 million compared to $22.2 million for the first quarter of 2021. Selling, general and administrative expenses include $2.2 million and $5.1 million of non-cash share-based compensation expense for the first quarter of 2022 and 2021, respectively. For the first quarter ended March 31, 2022, reported financing expense related to the prepaid forward obligation to RTW Investment was $5.8 million. As the transaction closed in May of 2021, there was no such expense in the first quarter of 2021. For the first quarter ended March 31, 2022, we reported a net loss of $28.4 million or $1.25 per share. This compares to a net loss of $25.9 million or $1.17 per share in the first quarter of 2021. The net loss for the first quarter of 2022 includes $2.9 million in non-cash share-based compensation expense compared to $6.2 million in non-cash share-based compensation expense in the first quarter of 2021. We closed the quarter with $147.1 million in cash, cash equivalents, and marketable securities. During the first quarter, we took important steps to further strengthen our balance sheet in support of our commercial and clinical development activities. We believe the closing of the up to $100 million term loan facility with the funds managed by Pharmakon Advisors has insulated us from what is currently a challenging capital market environment. With our fortified financial footings, we remain focused on commercial growth and execution in the clinic. Based on our current revenue projections and financial models, our current financial position and available tools provide us with what we believe will be sufficient runway to achieve cash flow breakeven by 2025. Turning to our financial guidance for 2022, we reiterate anticipated full year 2022 net product revenues from Jelmyto to be in the range of $70 million to $80 million, representing a 46% to 67% increase over 2021. We anticipate our full year operating expenses to stand in the range of $140 million to $160 million, including non-cash share-based compensation expenses of $10 million to $60 million, subject to market conditions. Lastly, we anticipate the full year 2022 non-cash financing expense related to the prepaid forward obligation to RTW Investments in the range of $22 million to $26 million, of which an estimated $9.1 million to $10.4 million will be paid in cash. With that, I'd like to turn the call over to questions.

Our first question comes from Ram Selvaraju from H.C. Wainwright. Please go ahead with your question.

Yes, thank you for taking my questions. I was wondering if you could comment on the timeline for completion of the uTRACT registry. And if you could elaborate a little bit on what specific ways in which the registry could be used to inform medical practice. Thank you.

Hi Ram, it's Liz. Thanks for the question. I'll turn it over to Jeff to sort of give you a timeline on uTRACT, but it will be kind of an ongoing thing because we'll continuously add new accounts. But Jeff, do you just want to talk about the kind of initial group of accounts that we have signed up?

Sure, no that is correct. It's going to continue. We're going to continue to add patients. And then, Ram good question. So once we have enough patients in each of those areas that we talked about, whether that's maintenance or whether that's an adjuvant setting, you'll start to see more data come from that. We did look at retrospectively a significant number of patients who are already in the registry, more than OLYMPUS, and we're looking to obviously publish that data in the future. So every time we get patients in, once the investigators feel like there's really enough there from a data perspective, we'll continue to generate data ongoing. So there's really no set timing when we're going to stop this. We're going to continue to keep the registry open, adding more accounts, and adding more patients.

Okay and then just a couple of other ones. Firstly, on the long-term financial guidance, I was just wondering if you could confirm, given the timeline for development of UGN-102 that the achievement of cash flow breakeven in 2025 could conceivably be achieved based on sales of Jelmyto alone? And then if you could give some additional context on the UGN-301 Phase I clinical development program, particularly in the context of how many potential combinatorial therapeutic regimens you expect to study within the context of this program? And if you could offer any specifics regarding what types of chemotherapy or immunomodulating treatments are likely to be utilized in conjunction with UGN-301 in the context of the Phase I study? Thank you.

Yes, sure. But to answer your first question, absolutely, we've said this all along, the company can be a profitable company supporting the entire pipeline with Jelmyto revenue. So to your point, our breakeven analysis is just based off of Jelmyto revenue. And so with that, I'll turn it over to Mark to give you some more context on Phase I and provide some more color around what we see as potential combinations. And these would just be sort of what-ifs because as we start to get more data, we'll home that in. But Mark, just want to talk about our initial thoughts around that.

Sure, and thanks for the question. So we have obviously talked about the initiation of the Phase I, which we're involved in right now, which will initially study 301 as monotherapy and then for the purposes of those findings. We're thinking, though, in terms of combinations, both of immunomodulators, which obviously would lead us to examine a combination with 201 or TLR-7 agonist, as well as other agents. And I think you heard Liz talk about this before. Clearly, we have experience with mitomycin. There are other chemotherapeutics like mitomycin that have utility and for which there is historic clinical experience in neurology in the treatment of urothelial cancer that would be attractive. And again, in the spirit of what-if, for example, gemcitabine. So immunomodulators are obviously on our radar like TLR-7 agonist. But also, other chemotherapeutics that could potentially provide us with an opportunity to perform effectively chemo-immunotherapy, which is something that's obviously very attractive given its relevance to the metastatic space. So there is predicate experience clinically. I hope that gives you a sense of where we would be going.

Great, thank you very much.

Thanks Ram.

Thank you. Our next question comes from the line of Boris Peaker from Cowen. Your question please.

Great, my first question is on your physician training. Can you comment on what fraction of your target physicians have already been trained for those that haven't been trained? What is the timeline do you think to get them through the training program?

Jeff, do you just want to talk about physician training? I'm assuming you're just talking about for Jelmyto installations, correct, Boris?

Yes, no so I would say, I mean, definitely thousands have been trained. What you're seeing now is a combination of both physicians training other physicians. And then we still have and will continue to grow our group of nurses. Our nurses do a phenomenal job of training the physician. So what you'll see in an account, let's just say you've got an account that one physician has used it and there's another physician that's identified a patient. More times than not, the nurse will be training that physician. But obviously, that physician will talk to the doctor that has treated a patient and may ask him or her some questions. But we're going to continue - as we continue to open up accounts - our nursing team does a great job in making sure folks are adequately trained. They are in probably 100% of the first installations and then it tapers off after that. The physician really only needs one or two installations to understand the installation and they take it from there. But the training will continue as we grow accounts and it can continue both within the practice as well as utilizing our nursing team.

Got it. And my second question is for your breakeven estimate based on Jelmyto for 2025, I'm curious, what is the revenue assumption there?

Yes, we have not provided revenue assumptions for peak for that. But suffice it to say when we look at our cash burn, which we've given guidance on, we don't expect meaningful increases over the next two years, right? We have a very efficient model, as we've talked about, we expect to keep expenses where they are in the range of where they are. And as we sort of bring down the clinical studies, we could have some savings there, but as we start new studies. So we expect our expenses to be - any increase to be fairly modest. So I think if you take a look at that, you can see we expect breakeven to be and what we need revenue to be so without giving specific guidance in there that sort of gives you a range.

Got it. And just lastly, have you taken any price increases on Jelmyto?

We did. Jeff, do you want to just provide the details on that? Very, very modest, and Jeff can explain more, I suggest.

Yes, because this is a buy-and-bill drug, even though the price increase was 1.5% in January. And you'll see those smaller, more modest increases moving forward just because of the buy-and-bill nature of the drug.

Got it, thank you very much for taking my questions.

Thanks Boris.

Thank you, Boris.

Thank you. Our next question comes from the line of Chris Howerton from Jefferies. Your question please.

Hi, good morning, congratulations on the progress and thank you for taking my questions. I have a clarification for you, Jeff, regarding your comment about seeing more bulk orders of Jelmyto. Could you define what that means and how it compares to your normal orders? My second question is related to the commercial side; we have noticed some labor supply issues in other areas of healthcare, and I'm wondering if those are affecting urology practices and the deployment of Jelmyto. Finally, I know we have discussed some potential combination partners for 301, but I would like to ask specifically if you have considered BCG and what that might look like as a combination moving forward. Thank you.

So Jeff, why don't you take the first two and then Mark, the third question? And thanks, Chris, how are you doing?

Yes, hi Chris, thanks for the question. So the bulk orders, what we see is a lot of these referral centers once they treat a few patients, they have a steady number of patients coming in, and they don't want to - they just - they want to be able to have the convenience of having the product there. So it tells me that one, obviously, they are a big referral center for Jelmyto. They can purchase in bulk and two, they have confidence. They wouldn't be purchasing Jelmyto if they didn't think they were going to be using it in the future. And so it's slowly growing, Chris, but it is growing. Obviously, still the majority of accounts prefer ordering one at a time. But it's something that I didn't really expect this early. And it's predominantly, as I said, in these referral accounts where they really know they're going to have that patient flow in the future, and they just want to have product there available to mix. And I apologize, your second question?

It was around kind of labor supply, if that's impacting urology practices if at all or your ability to deploy Jelmyto?

Yes, that's a great question. So it's getting better. We had - most of it was more in and around pharmacy, pharmacists coming back to work to make sure that we can mix. As you know, Chris, we have a mixing option. If we do run into issues at a hospital pharmacy, we've had to utilize that in a couple of instances, but it is improving as are rep access that continues to get better as well so as you see these mandates lifted. Folks are coming back to work, and it really hasn't been an issue in getting patients treated. It may delay treatment. I've talked before about the patient enrollment form typically taking - once that enrollment form is filled out, it takes anywhere between two and six weeks to get the patient treated. So in instances where there are labor issues, it may take a little bit longer, but we're not losing patients because of that. Mark, do you want to take the third one?

Yes Chris, thanks. As I think you know, there's a relatively new basic science research suggesting that CTLA-4 may be an important local targeted epithelial services including in the bladder. So that provides a sort of clear mechanistic rationale for our interest in locally applying anti-CTLA-4 in the context of urothelial cancer therapy. And as you point out, BCG and immunomodulators, which there is a really important predicate experience in neurology is an obviously interesting approach to treating this disease and one that neurologists have exploited historically. The combination of 301 and BCG is something that we are talking about internally, but it's probably a little bit premature for me to provide further detail about those discussions. But BCG is a very interesting drug in the context of treating non-muscle-invasive bladder cancer. I mean you're certainly talking about its role and its potential within the context of our immunotherapy program.

I think the only other thing I'll add is, Mark, can you comment on the continuing shortage of BCG, but we do think it's an interesting target and a potential combination. And I also think we're also thinking about the combination of immunotherapy, CTLA-4, and PD-1. And what would that look like as that's worked in many other tumors. But Mark, just want to comment, I think, on the BCG shortage, I think that's important to continue to hold on.

Sure yes, thank you. Yes, thank you, Liz. So I think as many of those who are listening would understand, BCG, which has been a hallmark in sort of a pivotal agent in high-grade non-muscle invasive bladder cancer for many decades is now in very short supply because of production issues. And this is an actual clinical problem. In fact, my practice will be now facing an acute shortage of this drug, which has precipitated real problems with delivery in patient care. So there is a real opportunity. And in fact, an urgent need to come up with alternatives to the use of BCG, and we are exploring those. As Liz points out in the context of thinking of other immunomodulator combinations as well as potentially utilizing BCG in various forms. There are a variety of forms of BCG available now. So it's very much on our radar and something that's important for this particular subset of the non-muscle invasive bladder cancer population. So we are actively thinking about this and working on it.

Okay. Well, that's very clear. And maybe if I'll sneak one in, when did Merck say that they were going to have that manufacturing site for BCG, do you guys know that?

Yes, it was like 10 years. It was several years away unfortunately.

Hi, good morning, thanks for taking the questions. I wanted to start off by asking about Jelmyto. Are you noticing the use of the nephrostomy tube in terms of how it is being utilized and its market uptake?

Liz, I'll go ahead. Yes, so the short answer is yes, and it continues to go up. We're going to have additional data to go along with what Dr. Murray has published with even more patients. And so it is increasingly becoming more and more popular to administer Jelmyto that route.

Okay, great. And then with respect to the ENVISION trial, how is site initiation ongoing? I guess you're targeting about 90 sites. How many sites do you have up so far?

Mark - I don't even know the number that we have actually active, but...

I don't think we've actually talked about the number of sites. We're on - yes, Matt, as you probably remember, one of the really fortuitous things about the ENVISION trial is it utilizes sites we had already initiated for the ATLAS trial. So we have a group of more than a small group. We have a very large group of educated and ready-go investigators at these sites who are very familiar both with the medication and the concept behind the trial. So although I don't think we know the exact number, we are charging ahead with this trial and fully expect to involve this year.

And that makes sense. It seems like that gives you a bit of a jump-start. And then in terms of the master protocol for the Phase I trial of UGN-301, can you talk a little bit about specifically what's going to work for incorporation of your 201, your TLR-7 agonist in that study?

Liz, let me take that.

Yes, please.

Yes, so the way this will work is we are starting with, obviously, 301 monotherapy to identify a dose and do some initial safety evaluations. But because of the way this is set up, we are able to - once the dose is defined and preliminary safety evaluations have been done, we can actually start combination therapy with 201. So it is staggered, but set up in such a way that we don't have to wait until we completely finish the monotherapy arm of 301 in order to initiate combination therapy. The monotherapy arm we expect will take 12 months. And again, that's starting this month. So we would expect that to be completed in the first half of 2023. But we will start the combinations before that. And as I said, our first combination will be with 201.

Okay, great, thank you and congrats on the progress.

Thanks Matt.

Thank you. Our next question comes from the line of Leland Gershell from Oppenheimer. Your question please.

Hi, thanks for taking the questions. Two questions, one for Jeff and one for Mark. Jeff, with reimbursement looking like it's quite broad at this point, high 90s percent, whether Medicare or private insurance, wondering what kind of key hurdles the commercial organization is addressing now with respect to kind of meeting the gap as Jelmyto continues in its launch? Is it geographic, is it a community versus more specialized centers? Is it simply some urologists kind of slower to change behavior patterns with respect to how they treat UTUC? If you could comment on that and how you're maybe focusing your efforts on addressing whatever those hurdles may be? And then also for Mark, just wanted to ask with respect to the ENVISION trial that is going to produce - is going to complete enrollment by the end of the year by your guidance. So we'd expect to see data from that trial by late next year with the NDA for 2024, actually to conduct kind of the first data cut we would see from ENVISION as you progress in that trial? Thank you.

Thank you, Leland. I'll address the first question. We've just completed a national sales meeting that provided excellent resources, including our FRM team, which can show reimbursement details on a state-by-state basis. When an account has inquiries about reimbursement, they can view the rising number of claims and paid claims across states. This will always be a priority for us. We want to maintain confidence in reimbursement, which is crucial. However, reimbursement is not the main reason we are not seeing broader usage, as you suggested. Right now, we are able to connect with more physicians within an account. Previously, during lockdowns or when access was limited, we focused on one physician as a champion. Now, we are expanding our reach to include more physicians, most of whom treat low-grade UTUC patients. If I had to quantify our focus, approximately 70% of our efforts are aimed at deepening relationships within existing accounts, where we've successfully onboarded a significant number. We will also continue to open new accounts. In fact, we've recently been added to a formulary at a major account in the Northeast, which is exciting. I've just learned they have 10 patients queued for treatment. Therefore, 30% of our efforts will be dedicated to opening new accounts, while 70% will focus on deepening existing relationships, facilitating greater access. We've discussed the importance of making five to seven calls on physicians. As you pointed out, some doctors may prefer surgical options, but the more calls our representatives can make with the available resources, the better the chance of persuading those physicians to consider Jelmyto for their patients.

Yes, and Leland, for the second question. So as you said, our plan is to enroll this year. It takes 12 months to get the initial sort of tranche of data that would be fundamentally useful for submission. The submission will take place in 2024 with approval expected in 2024 as well. Remember, we're also tracking patients who originally enrolled in ATLAS for the purposes of providing additional safety data for the submission, and we will have that data set as well. But I think I probably should defer to Liz with regard to the release of any additional information about the trial during that timeframe.

You won't see any data from ENVISION in 2023 because this is a trial, a pivotal study for the FDA, and the data must remain confidential throughout. As we enroll this year, and then have every patient by 12 months, we will start to see data in the first half of 2024. To Mark's point, we will share data on ATLAS in 2023, as we will use that data to support the submission. We will be able to share that data because those patients will have reached that time point. Additionally, we will share information about ENVISION and data from our home installation study for UGN-102 this year. We also have patient preference data showing that patients from our Phase II study mostly preferred UGN-102 and would recommend it to others. You can expect to see some data at the end of this year, data from ATLAS in 2023, and then more data in the first half of 2024. I hope that's helpful.

Yes, thank you.

Thank you. Our next question comes from the line of Anita Dushyanth from Berenberg Capital. Your question please.

Hi, good morning. Congrats on the progress and thanks for taking my questions. I would like to have a follow-up on the registry that you had talked about earlier in the call. So as you gain these insights from the uTRACT registry, do you plan to sort of incorporate any tweaks that might be relevant in the clinical practice? And then after which deal plan to then have this registry for 102 as well?

So yes, we will continue to take the data from the registry, take their learnings, and we'll absolutely be publishing those. We'll absolutely be incorporating those as appropriate. We also hope to use it to inform potential other studies that we may want to do or we may need to do to change the label or anything around that or if there's data that comes out of that. The registry is being done under a very strict protocol. And so, we hope that potentially if there's - we may even be able to talk to the FDA about using it if we need to use it to change anything in the label, although we have a great - we actually enjoy a very nice broad label right now. But particularly around safety and adverse events, I think it's really important. And Jeff mentioned earlier that we've got over 100 patients in a retrospective study as we started to set up the registry, and that will be published shortly, and I think you'll be really pleased to see some of the data coming out of that. So we will continue to do that. The idea is that and we mentioned earlier is to continue to grow the registry, so the more accounts that participate in the registry, the better. They like to see their own data. So not only will we be able to aggregate data across, but we'll actually be able to inform the actual accounts that are participating with their data and how their data looks like. And so, we'll be able to continuously use the data coming out of there for a lot of purposes. And then yes, absolutely, we would take that and add 102 whenever we launch 102. So thanks for the question.

Great, that's helpful. And then I just wanted to know, besides the metrics that you mentioned, would you be tracking like the different routes of administration and whether patients are using more of the nephrostomy tube or the injection every time?

Yes, Jeff, part of practice.

Yes, we will be. Obviously, we know because our nurses are in there, either training or retrograde or nephrostomy tube, and that will be, as Liz mentioned, a more robust data coming out in and around that. So certainly, yes, we know and yes, we'll continue to track. And yes, we'll continue to publish that data and get physicians more and more data. So they're comfortable if that's the way they would prefer to administer they have sort of data to support that.

Okay, great, thank you. And then last one about the 301 program. Is the goal to sort of investigate its potential in refractory populations with high-grade disease as a combination therapy and then maybe then move up to earlier lines of therapy?

Yes, that's correct. Yes, we would - the initial would be post-BCG. And then we would absolutely, depending on the data, we want to move it into front line as an alternative to BCG or in addition to BCG, as was mentioned earlier. Great. Thanks, Jeff and Liz.

Thank you. This does conclude the question-and-answer session of today's program. I'd like to hand the program back to Liz Barrett for any further remarks.

Great, thanks, operator. As always, we appreciate your support and interest in UroGen. We look forward to continue our pivotal year for us in 2022. So I hope you guys all have a nice day. Operator, you may disconnect now. Thank you. Thanks, everybody.

Thank you. And thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.