Urogen Pharma Ltd (URGN) 2024 Q1 法說會逐字稿

Good morning ladies and gentlemen. Thank you for standing by. Welcome to the UroGen Pharma first quarter 2024 earnings call. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your first speaker today, Vincent Perrone, Head of Investment Relations. You may begin.

Thank you operator. Good morning, everyone and welcome to UroGen Pharma's first quarter 2024 financial results and business update conference call. Earlier this morning we issued a press release providing an overview of our corporate highlights and financial results for the quarter ended March 31, 2024. The press release can be accessed on the investors portion of our website.

Joining me today are Liz Barrett, President, and Chief Executive Officer; Dr. Mark Schoenberg, Chief Medical Officer; Jeff Bova, Chief Commercial Officer; and Dong 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 Jelmyto, our ongoing and planned clinical trials, commercial and clinical milestones, market and revenue opportunities, our commercialization strategy and expectation, as well as potential future commercialization activities for UGN-102 if approved, anticipated data, including envisioned or ability data, regulatory filings, and decisions including UGN-102 potentially receiving priority review. UGN-102 being the primary growth driver for UroGen if approved; future R&D efforts, our corporate goals, and 2024 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. You are cautioned not to place undue reliance on these forward-looking statements, and your agenda disclaims any obligations to update these statements.

With that, I'll turn the call over to Liz. Liz?

Thank you, Vincent, and thank you, everyone, for joining us this morning. As we look ahead to 2024, we have several near-term catalysts, including the planned release of the 12-month duration of response data from the ENVISION study in June with our expected NDA submission this year.

We have assembled a strong body of data that demonstrates a compelling clinical profile for UGN-102. The ATLAS and ENVISION trials both met their primary endpoints, and if approved, we believe UGN-102 will advance the standard of care in low-grade, intermediate-risk, non-muscle invasive bladder cancer from repetitive surgery to a minimally invasive, routine, non-surgical option.

Our research reflects overwhelming support from both urologists and patients, with the intent to use by over 90% of surveyed urologists and over 90% of surveyed patients in the ENVISION study preferred UGN-102 to a TURBT. We are pleased to announce that we will host our virtual event to share the ENVISION durability data on June 13. The database lock will occur later this week, and we are very much looking forward to sharing the final results from ENVISION at that time.

Earlier this year, we announced initiation of a rolling NDA submission, and we believe the upcoming ENVISION data will support completion of the NDA in Q3 of this year, assuming priority review, we could launch as early as Q1 in 2025. The commercial opportunity is significant. We estimate that the overall market is approximately 10 times the size of the urothelial carcinoma market that Jelmyto currently addresses.

We intend to seek a broad indication for UGN-102. Conservatively, we estimate the size of the market opportunity to be over $3 billion. This represents a substantial market opportunity for our company and a chance to meaningfully impact the treatment paradigms and improve patient outcomes.

Our ongoing commercialization plan will include an incremental sales force expansion. Pricing analysis and market research are currently ongoing, but we expect pricing to be in the $16,000 to $19,000 range per dose. Given the response and feedback we have received, we believe patients will strongly welcome a minimally invasive non-surgical alternative to TURBT.

While we don't expect to replace TURBT in all patients, UGN-102 will be the first and only medicine approved for patients with low-grade intermediate risk non-muscle invasive bladder cancer, and we believe we'll offer an advance in treatment if approved. Jeff will provide more details on our commercial strategy in a few minutes.

In April, we announced FDA acceptance of the IND for UGN-103, an important next step in our lifecycle management strategy. 103 is our next generation formulation of UGN-102, which combines our proprietary RTGel technology with Medac's proprietary formulation of mitomycin.

A key aspect of this program is the potential for extended patent coverage for our next generation urothelial cancer franchise. Medac has intellectual property protection into 2035, and UroGen's pending US patent applications, if approved, could extend patent coverage until December of 2041. We are preparing to initiate clinical endpoint studies to support NDAs for UGN-103 and UGN-104, the latter being our next generation formulation of Jelmyto.

We anticipate dosing patients in the planned phase 3 trial of UGN-103 by end of this year, and UGN-104 shortly thereafter. As reported, Jelmyto revenues were $18.8 million for the quarter, an approximate 10% increase over Q1 '2023. More importantly, patient enrollment forms, or PEF, in Q1 were the highest ever, indicating demand continues to grow.

As we have experienced in the past, seasonality in Q1 results in a delay in patients being treated due to resetting of insurance. We have seen conversions accelerate in March and April, providing support for continued growth of Jelmyto. We are very excited by a recent post hoc analysis from the Olympus trial that evaluated the long-term efficacy of Jelmyto in patients who experienced a complete response.

Mark will elaborate on this momentarily, but at a high level, findings suggest that Jelmyto can offer extended disease-free periods, with some patients experiencing no recurrence for approximately 48 months. We recently released this data to the field and are optimistic about its impact with urologists.

Lastly, our balance sheet remains a priority and our cash position strong, with $164.5 million in cash, cash equivalents, and marketable securities as of March 31. Our capital allocation strategy continues to prioritize the ramp up of UGN-102 supply and its commercial launch alongside bolstering Jelmyto sales.

Our latest financial projections, assumptions, and sales forecast affirm our belief that our current balance sheet is robust enough to sustain our operations through anticipated break-evens, so we do not need to raise additional capital with our current plans.

Having said that, there is a plethora of opportunities to further study our medicines across new patient populations and position our company for longer-term sustained growth. We will remain diligent with capital deployment and opportunistically strengthen our balance sheet to accelerate and execute those potential growth opportunities.

I will now turn the call over to Dr. Mark Schoenberg, our Chief Medical Officer, for a clinical update. Mark?

Thank you, Liz. I'd like to start by previewing results from a not-yet published post-hoc analysis from the OLYMPUS trial Liz mentioned earlier. The post-hoc analysis evaluated long-term outcomes of Jelmyto use for primary chemoablation in patients with low-grade UTUC based on results from the OLYMPUS trial and a subsequent long-term rollover trial.

After receiving six weekly doses of Jelmyto, 41 of 71 patients in OLYMPUS achieved a complete response, and their health outcomes were tracked for up to 12 months. 20 of the patients remaining in complete response at 12 months enrolled in a five-year rollover trial.

Results for all 41 patients who initially achieved complete response indicated a promising median duration of response of 47.8 months based on a median follow-up of 28.1 months. Among the 20 patients enrolled in the long-term rollover trial, the median duration of response was not estimable as 75% of these patients continued to show no signs of disease recurrence or progression by the data cutoff date.

We plan to submit these results for peer review and look forward to sharing additional updates when available. UroGen had a significant presence at the recent American Neurologic Association meeting which took place in San Antonio with a total of four abstracts presented.

The first of these was a post-hoc analysis from the ATLAS trial of UGN-102 which was highlighted in a podium presentation by Dr. William Wong from NYU Langone. The analysis showed that UGN-102 used with or without TURBT improved disease-free survival and duration of response compared to TURBT alone.

This analysis revealed that both new and recurrent low-grade intermediate risk NMIBC patients who received UGN-102 achieved similar outcomes. Specifically, DFS rates were 77.4% for new patients and 63.2% for recurrent patients at 15 months while durable complete response rates were 87.5% for new patients and 69.1% for recurrent patients at 12 months.

Jelmyto was featured in three presentations at the AUA. This product is approved for the chemo ablative use in low-grade disease of the upper urinary tract. Independent long-term real-world analyses that were presented demonstrated 86% recurrence-free survival at 24 months with Jelmyto treatment for patients who responded to initial induction.

And there does not appear to be a difference in recurrence rates between anti-grade and retrograde methods of administration, original tumor size, multifocality, or tumor location. The long-term analysis also evaluated the value of maintenance use of Jelmyto. Although the analyses consisted of a 13-patient cohort, 100% of these patients maintained a complete response at 24 months. The authors concluded that administration of maintenance appears to be associated with significantly better recurrence-free survival.

I would now like to spend a few moments talking about the progress made in the UGN-102 program. As Liz mentioned, the next milestone for this program is evaluation of the secondary endpoint of the ENVISION trial, duration of response at 12 months following a complete response. We intend to share these results at a company-sponsored virtual event on June 13. Database log is scheduled for later this week, and we look forward to sharing the results next month.

I'd like to summarize the value proposition for UGN-102 and the rationale supporting our belief in the strength of our regulatory application and if approved, widespread adoption by urologists. UGN-102 has demonstrated consistency in the three-month complete response rate across ATLAS and ENVISION, as well as our prior Phase 2B study, OPTIMA 2.

Moreover, the ATLAS data suggests UGN-102 is superior to surgery once a complete response is achieved. In the ATLAS ITT population, 80% of patients who received UGN-102 plus or minus TURBT were still disease-free at 12 months following complete response, compared to only 50% of patients who had a TURBT alone.

A significant benefit of UGN-102 lies in its innovative RTGel delivery mechanism, which provides sustained release treatment directly to the bladder tissue for up to six hours. This extended dwell time facilitates treatment of both visible lesions and underlying abnormal cells that predispose to disease recurrence.

This attribute is critically important because, despite their expertise, urologists may not be able to detect all such cells during surgical procedures. We believe UGN-102 offers a clinically meaningful improvement over surgery in reducing recurrence risk and prolonging disease-free intervals for patients, while lowering the overall treatment burden on patients.

As Liz mentioned, we are actively advancing the development of next generation formulations of UGN-102 and Jelmyto. The investigational new drug application for UGN-103 was accepted by the FDA, enabling us to proceed to clinical trials. We plan to initiate a phase 3 trial of approximately 87 patients before year end.

Additionally, we are progressing with the development of UGN-104, a next generation formulation of Jelmyto, to begin sometime thereafter. Beyond our lead programs, we continue to develop our immuno-oncology candidate, UGN-301. UGN-301 is comprised of an anti-CTLA 4 antibody delivered using our proprietary RTGel technology.

We are conducting a phase one clinical study to evaluate the safety tolerability and establish a recommended Phase 2 dose for UGN-301 as mono, as well as combination therapy. We hope to report safety and tolerability data from the monotherapy arm by late 2024. We have also initiated combination therapy arms evaluating UGN-301 plus gemcitabine and UGN-301 plus UGN-201, our proprietary formulation of imiquimod, a TLR 7 agonist, in high grade NMIBC patients. We believe we have a unique approach in this area and look forward to providing updates as the program moves forward.

Now over to Jeff for a commercial update.

Thank you, Mark. Jelmyto net sales were 18.8 million in Q1. Seasonality trends in the first quarter, which are characterized by deductible resets in January and February, were magnified compared to prior years. As Liz mentioned, patient enrollment forms were the highest ever in Q1, indicating strong demand.

We're seeing an improvement in the conversion trend in Q2, with a normalized path to new patient start, leading to a reduction in the gap between enrollments and units sold. The data from the current quarter is on track with expectations of continued growth for Jelmyto sales and remain aligned with full year revenue guidance. We anticipate typical seasonality dynamics throughout the rest of the year.

As Mark stated, AUA was very productive, meaning with multiple data readouts reinforcing the value of Jelmyto. We have promptly integrated the post-talk long-term follow-up data from the OLYMPUS trial into our field operations to further enrich engagement with urologists.

These data, which complement the already robust body of real-world outcomes data, will serve as a powerful evidence-based resource, reinforcing discussions about Jelmyto's ability to deliver complete response rates and prolonged durable disease-free periods. For UGN-102, the pre-commercialization plan is well underway, targeting an early 2025 launch.

As we get closer to the approval date, we will add a modest number of additional reps to our existing field sales force. There's approximately a 95% prescriber overlap with Jelmyto, and we plan on leveraging our commercial organization to execute a streamlined launch.

As mentioned earlier, there's a strongly recognized unmet need amongst both urologists and patients for a new treatment option that has the potential to reduce recurrence risk and prolong disease-free intervals. Importantly, our research indicates a strong patient preference for non-surgical options that can reduce their overall treatment burden.

Supported by a simple method of administration and robust clinical data, if approved, we are poised to transform the way patients with low-grade, intermediate-risk, non-muscle invasive bladder cancer are treated. UGN-102 provides sustained chemoablation directly to the bladder tissue to treat both visible lesions and the underlying pathology.

The clinical data we have generated suggests that UGN-102 appears to be superior to the current surgical standard of care. We know that 70% of patients face multiple cycles of recurrence and surgical resection over time.

Our market research reflects urologist's concern about high recurrence rates and a strong desire for new treatment options that may prolong disease-free intervals. We also anticipate that economic factors will not hinder urologist's adoption of UGN-102 as the treatment will be delivered in the physician's office.

Our launch preparations are sharply focused on removing any logistical, operational, and financial barriers to use so that urologists can use 102 worry-free based on their conviction behind clinical merit alone. UGN-102 also has the advantage of being easy to administer, either by the doctor, nurse, or extender, offering a substantial benefit in terms of patient and doctor convenience. This streamlined approach enhances the experience for the patient and simplifies the treatment process considerably.

Based on market research, we believe the fastest adoption for UGN-102 will initially occur in three groups of patients. These are patients who have had multiple recurrences, those that would be considered surgical failures, patients with early recurrence, and patients who are ineligible or unwilling to undergo surgery.

Our goal for UGN-102, if approved, is to achieve broad adoption, and we are confident physicians will have a positive experience and broadly adopt. We will keep you updated as we address key insights into our plans as we prepare for launch.

I will now turn the call over to Dong Kim to discuss our financial results.

Thank you, Jeff. Revenue comprised of Jelmyto sales for the three months ended March 31, 2024, was $18.8 million, compared with $17.2 million in the comparable period in 2023. Cost of revenue was $1.7 million in the first quarter of 2024, compared with $2.3 million in the comparable period of 2023.

The overall decrease of $0.6 million is primarily attributable to certain non-recurring payments made in connection with our supply arrangement in the prior year, decreased in mixing fees, and decreased in the Jelmyto per unit cost.

R&D expenses were $15.5 million and $12.5 million for the first quarters of 2024 and 2023, respectively. The year-over-year increase was primarily a result of regulatory-related expenses in connection with UGN-102, as well as R&D expenses in connection with the initiation of our Phase 3 study for UGN-103. Selling general and administrative expenses for the first quarter of 2024 were $27.3 million, including non-cash share-based compensation expense of $2.2 million.

This compares to $24.5 million, including non-cash share-based compensation expense of $1.8 million for the same period in 2023. The increase year-over-year was primarily attributable to UGN-102 brand marketing costs.

Interest expense was $2.4 million and $3.6 million for the first quarters of 2024 and 2023, respectively. The decrease was primarily attributed to the decrease in the margin interest rate and the related impact to amortization of the discount on the Pharmakon loan as a result of the amended and restated loan agreement in March 2024.

Net loss was $32.3 million, or $0.97 per share, and $30.2 million, or $1.30 per share, for the first quarters of 2024 and 2023, respectively. As of March 31, 2024, we had $164.5 million in cash equivalents and marketable securities. During the first quarter, we utilized our ATM facility for gross proceeds of approximately $56 million.

Today, we are reiterating our full year 2024 net product revenues guidance from Jelmyto to be in the range of $95 million to $102 million. We expect full year 2024 operating expenses in the range of $175 million to $185 million, including non-cash share-based compensation expense of $6 million to $11 million, subject to market conditions.

The anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW investments are expected to be in the range of $21 million to $26 million. Of this amount, approximately $12.4 million to $13.3 million is expected to be in cash.

For further details of our financials, please refer to our quarterly report on Form 10-Q, which has been filed with SEC.

We are now ready to open the call for questions. Operator?

(Operator Instructions) Tara Bancroft, TD Cowen.

Hi, good morning. So, I'm wondering if you could tell us approximately how many patients are included in each of the three buckets that you mentioned of initial adopters and which of those you think may be the most robust users? And then-- from there, how do you imagine adoption to look over time, especially as you continue your education and awareness efforts?

Thank you. Jeff, why don't you take that?

Yeah, thanks, Tara. So, the unwilling or unfit for surgery is around 10% of patients. We believe that's a conservative number because, really-- there are no other choices but to have to do a surgery. But in a conservative number, around 10% to 15% are unwilling or unfit for surgery.

About 25%, 23% from Medicare data tells us that they have five or more recurrence. So, you're frequent recurrence. And then, that same number is also early recurrence. So, a quarter of the patients will have a recurrence within 6 to 9 months. So, a good number of patients that physicians have told us, really, UGN-102 will have a benefit for.

And then, your second question was around adoption. Certainly, I think those three areas will be where it's adopted the soonest. And then, it's imperative that the commercial team drive that adoption to have 102 available to every patient-- depending on the label, whether it's newly diagnosed or someone that's had a previous TURBT.

Yeah, and I guess the only thing I'll add to that is we do expect the adoption curve to be faster than what we've seen with Jelmyto for a few reasons, that mainly what Jeff has talked about in the sense of how much easier it is to give.

And that being the case, -- and the knowledge and experience that a lot of these physicians already have with our current medicine. So, we expect that to be much quicker than it was for Jelmyto. But even if it were the same adoption curve as Jelmyto, again, being 10 times the size, you can do the math, right?

If you look at what we did last year, over $80 million in revenue for Jelmyto, if you just said it was the same in third year on the market, what would it look like? It's something like that. So, that would be a good analog.

Okay, thanks so much.

(Operator Instructions) Raghuram Selvaraju, H.C. Wainwright & Co.

Thanks very much for taking my questions. Just with respect to reimbursement for UGN-102, I was wondering if you could give us some granularity on the following. Firstly, do you think that there might be potential upside to your envisaged pricing range and what factors might influence that from a clinical data efficacy profile perspective?

Secondly, maybe Jeff, you could explain a little bit about how a [J-code] might work in the case of UGN-102, or if it's not applicable, why it might not be applicable?

And then lastly, if you're talking about an incremental expansion of the sales force, can you just remind us what the sales force headcount is currently and how you expect that to change as and when UGN-102 is approved and being launched? Thank you.

Sure, thanks, Ram. I'll take this first one on pricing and then turn it over to Jeff for the other two questions. But yes, we do see upside versus what we've communicated in the past. I think it's going to be a real balance. Again, this treatment is for low-grade disease, so low-grade disease versus high-grade disease, so the pricing is different, but we absolutely will--and I think the final data that's going to be shared in June will also have an impact on that. So, to your point, what factors impact it?

Obviously, when our data came out last year, we had already done pricing research. That gave us an opportunity to push the upper bounds of that. And I think, given the data that we expect in June, may be the same thing. So, we will finalize the pricing-- obviously, before launch, but we haven't now.

But I can tell you that we're looking at a higher range and even a little bit higher than what we've talked about in the past. So, Jeff?

Yeah, and let me comment on the J-code. So, yeah, we will eventually have a permanent J-code. Like all Part B drugs, though, we will have a miscellaneous code until CMS reviews. The nice thing, as we saw with Jelmyto, we were approved in the second quarter of 2020. You then apply for that permanent J-code the following quarter. They take a quarter to review, and we had a permanent J-code January of 2021.

So, depending on our approval timing, that will be the process. But the nice thing is that they're reviewing these quarterly now versus annually. So, I expect that same process to take place for UGN-102.

Current headcount, we do have around 7regions, 45 territory business managers. Those are the reps, supported by reimbursement team, nurses, as well as key account directors and FRMs. We will expand one region. We will go from 7 to 8. And we're kind of finalizing right now the number of representatives, but anywhere between 10 and 15 representatives as well, followed up by those support functions as well. So, hopefully that helps.

Very helpful. And just as a quick follow-up to that, I don't know whether Liz or Dong, you want to comment on how you expect the GNA infrastructure of the company to change in the wake of UGN-102's approval, or if you don't really expect much change on that front.

Thank you. Yeah. Dong, do you just want to comment on GNA?

Absolutely. So, thanks, Ram. So, basically, we don't see actually that much difference after this year. So, this year, we are going to spend some money to build an inventory and build some sales force, but then it will be pretty consistent. Liz, do you want to add?

Nope. I think that's correct.

Thank you,

Matthew Kaplan, Ladenburg Thalmann & Co.

Hey, good morning, guys. Just as we-- now we're nearing month out, the ENVISION study, 12-month durability data. Can you give us a little bit more detail in terms of what we should be looking for? And then, Liz, you commented on, depending on that data, some pricing upside and what would drive that in terms of the durability data as well?

Yeah. So, I mean--I guess I'm not really sure if you're saying what do we expect the number to be or what do we expect to see. Just from a perspective of what you'll see, obviously, we'll share the 12-month durability and any update on safety and what our current expectations are even beyond. So, we'll be estimating. So, we'll be able to share estimates of median, where we expect the median to be.

And so, -- a lot of great data. And my point around pricing is, obviously, the better that data is, the better value that we'll be giving patients and physicians and the practice and the healthcare system. And that will-- that's where we've been from a pricing standpoint.

So, that's our expectation. For what would be, quote-unquote, a win-- I would say, without saying too much, we believe that if you look at the ATLAS data and where we were on the 12-month data there, those patients are 69% for all recurrent patients and the patients that had a prior TURBT was 66%. So, anything in that area or above, we would definitely feel like would be a home run. So, we're excited, again, to share that data in June.

Thanks, Liz. That's really helpful. And then, in terms of, maybe for Dong, the impacts of the discounts associated with the Medicare refunds and for unused drug and 340B purchases, what was the magnitude of that impact in the quarter? And then, what should we expect kind of going forward throughout the year?

Yeah. So, Dong?

Yeah. So, I think it's probably better-- Jeff to answer, but in general, we expect a similar number in terms of overall gross net, but we got more specifically like 340B or the wastage provision, we expect more favorable to UroGen for 102 over Jelmyto.

And Jeff, Liz, do you want to add anything?

Yeah. I think the percentage for Jelmyto will remain the same from the wastage provision. Obviously, the more we sell, that will be impacted, but I don't see 340B. It does vary quarter to quarter, but I just want to reiterate, Matt, that 102 should not have that, either one of those impacts.

The bladder can expand and we can deliver all of 102, so we won't be impacted there, as well as most of this will eventually be given in the clinic, so not as impacted from a 340B standpoint.

Okay. That's good. And then, last question, maybe from Mark, in terms of development pathways for next-gen products, 103 and 104, I guess, what will it take to get these products in market? Are you contemplating just single Phase 3 studies for each?

Matt, thanks. So, I think it's probably a little bit premature for us to say exactly how this is going to play out because we are, as you know, not only developing information about 301 or for monotherapy, but the basis of this program is really a combination program using two drugs of different types, so it might be a combination immunotherapy with two different immunomodulators, immuno plus chemo.

So, we know we're going to have, as Liz has alluded to earlier, safety data and a Phase 2 recommended dose later this year, and we'll report on that for 301, but as we elaborate more data on the combinations, we'll probably be able to talk a little bit more about what the development pathway looks like for the most promising of these combinations. It's probably as much as I should say, but Liz may want to comment as well.

No, nothing additional unless you, Matt, had any additional questions. Just making sure you were talking about 301 and not 103 and 104.

Yeah, I had kind of targeted 103, 104, but-- (multiple speakers)

I'm sorry. Yeah, I apologize. Yes, single Phase 3 studies smaller than what we were required for our original approvals, smaller, for example, than envisioned, but we expect Phase 3 studies to be adequate to achieve approval for those new next-generation products for both Jelmyto and for 102. Sorry, I misunderstood the question.

Yeah, which is why we expect the approval to be obviously much quicker because, we don't have to enroll as many patients, and therefore-- our enrollment,-- we will finish our enrollment, for 102 and 25, and therefore have follow-up and filing in '26 for UGM-103, which is the next generation for UGM-102.

Yeah, got it. Thanks guys.

Thank you.

Thank you. Leland Gershell, Oppenheimer & Co. Inc.

Hi, good morning. Thanks for taking our questions. A couple from us. First, the company in the past has said that there's sort of a 50% bar with respect to this, 12-month durability data from ENVISION. I'm just wondering how we should best interpret what that means when you say bar and how we should think about that number versus the higher numbers that you mentioned through the character on this call with respect to level of enthusiasm for urologists to adopt 102.

And then just another question for Mark. I wasn't sure if you would mention when we would see the data, and if it's going to be data for 301. We would like to know when we might see that. Thank you.

So, Mark, do you want to talk about sort of the 50% that we've always talked about, kind of our expectations?

Yeah, sure. Liz thanks. So, with respect to the bar, maybe just to clarify, and I think many people on this call have heard Liz say publicly before that when we started the 102 program, the 50% number was a number we came up with as a projection of what we thought would be clinically meaningful. We know from conversations with urologists, and I can say independently, -- from a clinical perspective, that a number lower than that would be clinically meaningful in terms of its practical utility in taking care of this chronically recurrent patient population. Nonetheless, this 50% number was our projection.

Now, as you noted, the data we've provided from our clinical trials are actually better than that 50% number. And as Liz was saying, remember also that ENVISION, unlike ATLAS, ENVISION is a pure recurrent population of patients.

So, when we look at the Atlas subgroup of recurrent patients, we know for those who had a prior TURBT, and that is essentially the ENVISION population in microcosm, the durability data were 66% at that important 12-month follow-up time point.

So, we think, as Liz said earlier that something in the mid-60s is likely to be-- what we would be looking for and what we would consider to be very successful and consistent with our prior experience. So, again, the 50% was a projection. The 66% is what we actually know empirically from our own clinical trials program.

That's what we're projecting. We'll see if something like that in ENVISION. And then, just to answer the final question with respect to 301, later this year is what we've said in terms of when we'll be able to provide safety data and a recommended phase 2 dose.

When exactly is not clear, but likely, certainly by the time we have the SUO meeting at the end of the year, which is where we would probably present those data. I hope that's helpful.

No, thank you. And then one more, if I may, given other chemo agents, like the Gemcitabine, [Dostinex], regimen, and BCG and IU high-grade shown to have benefits, I'm wondering if you're looking at other chemo agents as part of the gel formulation compared to gel time and perhaps better results. Thank you.

Liz, do you want to talk about that?

Yeah, please go ahead.

Yeah. So, Leland, if I understood you, the question is, have we thought about putting Gemcitabine in the gel? And the answer is, we've certainly talked about this. Liz may want to comment on some of the commercial NIP issues related to that. But we know from a formulation perspective that our chemists are able to formulate a lot of different drugs in the gel.

As we've said before, we know we can do combination therapy as well, where we can put more than one agent in the gel. So, we've certainly had that conversation. But again, I'm going to defer to Liz with regard to any future plans regarding the formulation of GEM in the gel.

Yeah. So, the comment I'll make on GEM specifically, but then I'd like to-- just comment on kind of the broader utility in other ways. There won't be any IP protection by the time we would get to market. So, Gemcitabine in our current gel is not something that we would be moving forward with.

Having said that, we actually are in the process of looking at many other agents that are either in the market or in development in the market-- frankly, at all stages and all types, whether it be chemotherapy or target agencies or viruses, we're doing a whole landscape about-- what would be our next product, but particularly as we move into high-grade disease.

And the 301 program, very important in high-grade disease, because we do have long IP with the CTLA 4. So, anything in combination with that would allow us to have-- would allow us to have that-- that's the case and that being the case, which is why you'll see that and you'll see combinations with CTLA4 that will give us some IP as we move into high-grade disease.

So, a lot of things that we're looking at, both for low-grade disease and for high-grade disease many different, I think the complexity of bladder cancer is not necessarily really understood and appreciated by everybody, but there are a lot of different patients. And as you start to look at the [hard] data, you start to look at the CG data-- it really, really does show that-- really does show that everything works in different patient populations in different ways.

And so, we will definitely be prosecuting multiple products as we go forward across these many different patient types. But, looking forward to hopefully sharing more about that later in the year as we prioritize, where we want to go next.

But, and then also suffice it to say that-- given what we expect with UGM-102, there's also, opportunity to move UGM-102 into high-grade disease. But even within populations like unwilling and unable and the broader low-grade, low-risk patient population, there's opportunity in this space, and we expect to begin to prosecute against that with our priorities, obviously, being our next generation, which allows us --that extended IP allows us to do more with UGM-103 and UGM-104. So, hopefully, that's helpful, Leland.

Thank you.

Thank you. Paul Choi, Goldman Sachs Group, Inc.

Hi, everyone. Thank you so much for taking our question. This is Khalil calling in for Paul. I guess a quick confirmative question for us and then a quick follow-up. You mentioned that the potential commercial launch of UGM-102 might be more rapid than Jelmyto, just given the prescriber overlap and the slightly higher sales force. Just wondered if you could, like, maybe add some granularity on that and maybe just confirm that's what you're trying to say.

And then, for 301, you mentioned that you might provide some safety data later this year. That's for the monotherapy data. Any granularity on the timing of when you might provide an update regarding the combinations and just maybe some more granularity on your general idea about expansion into higher-risk populations or high-grade disease? Thank you so much.

Sure. Yeah, I'll just, turn it over to Mark to talk about 301 and sort of what our expectation is there, and then Jeff can answer the first question. So, sorry, going backwards, but go ahead, Mark.

Yeah, sure. Thanks, Liz. So, as Liz has said earlier in the call, the 301 program is targeting high-grade disease, and as I'm sure the audience is aware, when you start looking at patients with high-grade disease, the natural place to take this sort of a program would be into the BCG-unresponsive or refractory population. So, with respect to timing of data on 301, again, that's probably the end of the year.

The combinations sometime in 2025, we haven't been more specific than that, but we will provide whatever we have on those combinations with respect to any kind of efficacy, signal, and safety data that we would have in 2025. And then, in terms of the program, my expectation, Liz may want to comment as well, is that this would then roll out into initially a BCG-refractory population of patients for a variety of reasons, but that seems to me to be, from a clinical perspective, the most logical fit for a first approach to that population of patients.

Thanks, Mark. And, Jeff, you just want to talk about, the adoption of UGM-102.

Yeah, I think the biggest,-- the one thing we hear with regards to Jelmyto is just the number of patients that are out there, and physicians will tell us, particularly with this data that we saw from AUA, they're very positive in and around, the four-year long-term,-- medium-long-term follow-up.

But the biggest objection we get is, I just, I don't have a lot of these patients. We won't have that with 102. In fact, we've seen in market research, instead of two to three patients a year with Jelmyto, they have two to three patients a month that fit the intermediate risk category.

And so, the most common, I don't even call it objection, but, it is-- I like what I hear clinically about Jelmyto. I just don't have many patients. We won't hear that. And then the second, as Liz alluded to earlier, the operational list. So, these accounts already are-- they'll have BCG days, they'll have gemcitabine they'll,--they have days where they'll bring in these patients, the nurse or extender will give the dose and will fit right into that,-- that sort of already established way operationally that they treat.

And so, a lot of this will be given in the clinic. We won't have as many hospital bureaucracies to get through formulary. Obviously, we'll support that. If they want to give it in the hospital, we will support that and get it on formulary. But the operational list is much different. And then the objection of I don't have a lot of patients goes away.

Got it. That's helpful context. Thank you so much.

Thank you. I'm showing no further questions at this time. I'd like to turn it back to Liz Barrett for closing remarks.

Thank you. Thank you, operator. Thanks again for everybody joining us today. I just want to reiterate how excited we are with the data that was just presented at AUA. It was a great AUA for us. And very importantly, as I mentioned, and Mark as well, we're really looking forward to the data event on June 13. So, hope to see here, see all of you there, although virtually, but hope to see you there. So, have a great day. Operator, you can now disconnect.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.