enGene Therapeutics Inc. ($ENGN)

Good morning, and welcome to the EnGene Therapeutics LEGEND Pivotal Cohort Update. As a reminder, this call is being recorded, and a replay will be made available on the EnGene website following the conclusion of the event. I'd now like to turn the call over to Lauren Hopfer, Executive Director of Investor Relations at EnGene Therapeutics. Please go ahead, Lauren.

Thank you. Good morning, and thanks, everyone, for joining our call to discuss the data we press released this morning from the pivotal cohort of our ongoing Phase II LEGEND trial of detalimogene voraplasmid, or detalimogene, in high-risk BCG unresponsive NMIBC patients with carcinoma in situ. The company recently posted a slide deck on its website which we will refer to during this call. These slides are available on the Events and Presentations section of our website. Joining me on the call this morning are Ron Cooper, Chief Executive Officer; Hussein Sweiti, Chief Medical Officer; and Amy Pott, Chief Global Commercialization Officer; and Ryan Daws, our Chief Financial Officer. Before we begin, I would like to remind you that during our prepared remarks and the Q&A session to follow, we may make forward-looking statements for purposes of the U.S. and Canadian securities laws. These statements include, but are not limited to, our current expectations regarding the potential benefits of detalimogene, timing of clinical data, timing of regulatory submission and the prospects for regulatory approval of detalimogene. They involve risks, uncertainties and assumptions that are difficult to predict and may not prove to be accurate. Results may vary. These statements should be considered only in conjunction with the information in our filings with Canadian and American securities regulators, including our Risk Factors section of our annual report on Form 10-K. At this time, I'll turn the call over to Ron Cooper, EnGene's President and CEO. Ron?

Great. Thank you, Lauren, and thanks to all of you for joining the call. Our primary focus today will be to review the latest data from LEGEND's pivotal Cohort 1, an overview which was press released this morning and will be presented during a plenary session at the American Urological Association Annual Meeting next Friday, May 15. As most of you are aware, we announced that we had completed enrollment of 125 patients in Cohort 1 last year and provided a preliminary data update. It focused on detalimogene's excellent tolerability, ease of use and the improvement seen in complete response rates from 62 of 94 patients enrolled following a protocol amendment implemented in the fourth quarter of 2024. Data from this update demonstrated an improvement in any time, 3- and 6-month CR rates compared to the pre-protocol amendment patients. As of the November 2025 update, there were 32 patients enrolled under the amended protocol who had not yet reached their first disease assessment. In today's data update, you will see that these patients did not respond as well as the initial 62 patients. Preliminary analysis did not show a material difference seen across patient characteristics during subgroup analysis. Following the November 2025 update, the overall re-induction success rate was lower, and fewer patients opted to undergo re-induction. Work is already underway to conduct a deeper review of the data. Now that being said, detalimogene's current CR at any time, our primary endpoint, and the Kaplan-Meier estimated 12-month CR rate are currently tracking within range of approved products. The data are not yet fully mature, and the durability picture is incomplete. Given the compelling tolerability profile and ease-of-use benefits for busy urologists, we plan to await longer-term durability data for all of Cohort 1 in the second half of the year and continue our ongoing discussion with the FDA regarding both our statistical analysis plans and plans for a potential BLA filing. As Amy will touch on shortly, our ongoing market research continues to show that there's both a desire and a need from urologists and patients alike to have additional bladder-sparing options that are tolerable, easy to use and reduce the overall burden for patients. I'll now turn the call over to Dr. Hussein Sweiti, our Chief Medical Officer, to discuss our preliminary data in greater detail. Hussein?

Thank you, Ron. Beginning here on Slide 4, we thought it is beneficial to give you an overview of exactly where we are in LEGEND at this point in time. As Ron noted, the data we are outlining today is still preliminary,, and follow-up is ongoing. As you can see from the CONSORT diagram, we enrolled 125 patients, with 124 having completed the 3-month assessment. This diagram illustrates patients at different stages of the ongoing study, with a number of patients still awaiting 9- and 12-month assessments. Slide 5 is an overview of Cohort 1's patient demographics and disease characteristics. The median age was 71 years. Just over 80% of the population was male, and the median number of BCG doses received prior to enrollment was 12. As highlighted on the slide, our patient population as a whole has a number of high-risk characteristics. Almost 40% had CIS plus papillary disease, and 25% received prior therapy other than BCG. While the median number of NMIBC recurrences was 2, some patients had recurred as many as 11x prior to enrollment. On Slide 6, I'll cover a topic we believe to be very important when treating high-risk NMIBC, which is tolerability. Detalimogene's favorable safety and tolerability profile has remained consistent throughout our trial, with 55% of patients experiencing a treatment-related adverse event, most of which were mild, Grade 1 to 2, localized and resolved quickly. The most frequent TRAEs were fatigue, dysuria, pollakiuria, micturition urgency and bladder spasm. Only 6 patients had a Grade 3 or greater treatment-related adverse event, all of which resolved. The tolerability profile is best illustrated in the low treatment discontinuation rate due to TRAEs of 2.4% and the similarly low treatment interruption rate due to TRAEs, which was also 2.4%. We believe tolerability plays an important role as providers and patients assess their treatment options. BCG, as well as other agents, can be highly irritating to the bladder, and toxicity can be cumulative over time. Now on Slide 7, I will cover efficacy. The following table is representative of Cohort 1's population in its entirety. With 1 of the 125 patients dropping out prior to the first post-baseline assessment, we have a total of 124 evaluable patients at the April 21 data cutoff. Complete response at any time was 54%, and 43% at the 6-month evaluation. Of the 52 patients who were responders at 6 months, at the 9-month assessment, 37 of 44 evaluable patients were in CR, with 9 patients pending their evaluation. At the 12-month disease assessment, we had 13 of 22 evaluable patients in CR, with 11 patients pending their 12-month assessment. While you can see that we have provided complete response rates at 9 and 12 months of 33% and 13%, respectively, these data sets are still immature, and thus, we have also provided their respective Kaplan-Meier estimates. We plan to provide an update on these longer-term CR rates in the second half of this year. I will remind you that this is a data analysis at a point in time, and it will evolve. For example, there is a patient that at the 9-month assessment, had a non-CR according to the database, but has since been confirmed and updated by the investigator to be in complete response. As you can see on Slide 8, the 32 patients who had not yet undergone their first disease assessment as of November 2025 Cohort 1 update had an any time CR rate of 39% and 32% at 6 months. This is lower than the any time CR rate and the 6-month CR rate previously reported in both the pre-amendment and post-amendment subpopulations that have been previously reported. This also results in a marginal overall difference between our pre- and post-amendment subpopulations. There were no discernible differences between demographics or disease characteristics of this subgroup of 32 patients from those previously enrolled, and we are undertaking further analysis to see if we can determine a reason for the lower response rate seen in this population. We designed detalimogene to meet the unique needs of community urologists and are continually looking for ways to improve efficacy and increase convenience. On Slide 10, I'd like to discuss the use of bladder wash to potentially improve efficacy and reduce dwell time. Our proprietary sugar, or DDX, is designed to penetrate the mucosal layer and transfect the urothelium. The surfactant bladder rinse can disrupt the mucosal barrier and further increase DDX penetration and transfection. Other products have used surfactants to increase the magnitude and duration of transgene expression. On Slide 11, we have now data from multiple preclinical models, which show that a 5-minute bladder rinse with polidocanol, an approved sclerosing agent, achieved a tenfold increase in IL-12 expression over a 2-week period, shortened dwell time and improved efficacy. Given the strong preclinical data, you will see here on Slide 12, an overview of a new cohort we recently added to LEGEND incorporating this bladder rinse. We now have 20 trial sites activated, and screening is underway to enroll up to approximately 80 patients. While the dosing frequency of detalimogene given at weeks 1, 2, 5 and 6 will remain the same, you can see that the total overall dwell time has been reduced from 60 minutes to 30 minutes, reducing the burden on patients to hold treatment in their bladders, which can often be challenging given reduced bladder capacity and elasticity due to aging and disease. In summary, while these data are still preliminary, detalimogene continues to demonstrate favorable tolerability and clinical activity in a heavily pretreated, high-risk patient population, with disease progression being rare. While we acknowledge that the patients assessed following our October 2025 data analysis had lower CR rates, we await expected top line data in the second half of this year and plan to conduct a thorough analysis and discuss our findings with the FDA. In the meantime, we're also underway with enrollment of our surfactant bladder rinse cohort, and we plan to provide an update on expected time lines for enrollment and data once we are able. I'll now turn the call over to Amy Pott, our Chief Global Commercialization Officer, to discuss some more of the insights we have uncovered from our ongoing market research. Amy?

Thanks, Hussein. Our commercial team has been conducting in-depth market research, the results of which have been confirmed and built upon our key assumptions for the HR NMIBC market. First, on Slide 14, while we previously confirmed our thesis that the vast majority, over 80%, are being seen in community settings, which includes small private practices, large urology group practices, or [ LUGPERs ], and health systems and hospitals, what we are now seeing in our survey data are the stark differences in resources and ability to manage patient flow and treatment effectively. A typical urologist in a small private practice manages an average of 12 NMIBC patients compared to just 6 by an academic, yet academic centers have a patient-to-procedure room ratio of 10:1 compared to 24:1 for a small private practice and 19:1 at [ LUGPERs ]. These smaller practices are overwhelmed with patient load but have fewer resources to manage these patients, resulting in high opportunity costs for clinician time and facilities use. On Slide 15, we surveyed 100 urologists across practice settings, the result of which indicate that less than half of urologists across all settings are prescribing novel branded therapies. As noted, some urologists practicing in smaller settings will prescribe and treat patients with novel products, but are often forced to refer patients to local hospitals or other providers in order to administer therapies that require more infrastructure than available to them at their practices. In turn, this means that the urologist is unable to benefit from potential buy-and-bill revenue. On Slide 16, you can see that two of the key reasons for limited use of these new therapies include the difficult logistics and acquisition costs. On Slide 17, detalimogene is uniquely suited to solve the challenges for community urologists. For busy resource-constrained practices, this could open up a new opportunity to recognize optimal access and reimbursement, such as buy-and-bill. With that, I'll turn the call back over to Ron.

Great. Thanks, Amy, and thanks, Hussein. So I'd like to close by making a few points here on Slide 18. So as Hussein mentioned, our plans are to complete the pivotal cohort, enroll the study incorporating surfactant bladder rinse and engage with the FDA with the final pivotal cohort results. One way to think about that engagement is to draw upon efficacy and durability points of recently approved products. For example, you can see that our CR at any time of 54%, Kaplan-Meier estimated 12-month landmark CR rate of 25% and median duration of response of 8.7 months are aligned with Adstiladrin. The current 12-month duration of response KM estimate is 25% with a 95% confidence interval of 11% to 41%. Again, longer-term data remain immature at this point and are subject to change with additional analysis and time. The emerging profile of detalimogene is starting to become clear. The tolerability profile remains attractive, with most of the AEs being mild and predominantly associated with catheterization. Our updated data demonstrates efficacy, but it is at the lower end of our expectation. However, it is preliminary and will evolve as we complete the study. In addition, based on the results of our preclinical models, we believe that a surfactant bladder rinse combined with detalimogene could improve efficacy and reduce dwell time. This study is enrolling, and we look forward to sharing the data. What's clear from these recent market research and survey insights is that community urologists have the fewest resources, their adoption of the newer agents remains low and that there is a place for a product that does not have burdensome logistics and can be easily acquired. As the only nonviral gene therapy, detalimogene has the advantage of being stored for years in a regular freezer and for months in an office refrigerator. We've recently completed all of our at-scale FDA validation manufacturing batches and anticipate having the lowest cost of goods across NMIBC immunotherapies. Detalimogene could meet an important need for the busiest community urologists if ultimately approved. Thank you for joining the call today to discuss this preliminary analysis. We're looking forward to the plenary session at the upcoming AUA meeting and engaging with the medical community. Operator, I'd like to now open the call for questions.

Great. Thanks, Ron. [Operator Instructions] So our first question comes from Maury Raycroft at Jefferies.

Maybe just starting off, wondering if you could talk more about the path forward from here and how we should think about next steps for FDA engagement? And can you also remind us how you view FDA's latest thinking on the potential for a single-arm study for registration and whether they have commented on a specific efficacy?

Maury, thanks very much. I'll take both of those questions. Let me take the second question first, right? So I think from a single-arm perspective, remember that the FDA in this category issued draft guidance in 2018, and in 2024, reiterated that draft guidance. And since that time, our product has been approved in this pathway. And this pathway is not an accelerated approval, it is a full approval. So it's different from some of the other issues that have occurred with accelerated pathways. So we believe this pathway is intact. And of course, we've had a lot of dialogue with the FDA given that we have RMAT status and CDRP, which are unique, right, and real honors for us. And if I look at our engagement with the FDA, they've been very much engaged with us. So I think we feel that the path is strong. Now in regards to engagement with the FDA, we have had a number of engagements with the FDA, particularly because we have this RMAT status and CDRP. We've been having a good dialogue around our manufacturing, given that we have finished our PPQ batches or the FDA validation batches. So that is ongoing. As it relates to the data, our plan is to continue our dialogue on the statistical analysis plan. So we're back and forth with the FDA on that, and we'll finalize that over time. And then once this data set matures, the Cohort 1 data set is fully mature, we'll engage with the dialogue with the FDA. Thanks for the questions, Maury.

Okay. And so presumably, that engagement would probably be later this year than that -- kind of the second half?

Yes, exactly.

Part of the second half plan?

It will be part of the second half.

Okay. And then maybe just a question on the heterogeneity and response that you're seeing, appreciating that it's still early data. Do you have any visibility into what may be driving the differences observed amongst the newly assessed patients? And presumably, it seems like you think it could be something related to expression. Do you have any evidence indicating this?

Yes. So as I mentioned during the presentation, we did a preliminary subgroup analysis looking into key disease characteristics and demographics, and we did not so far identify any factors that could have contributed to the worse outcomes for patients in the last group of patients, the 32 that we referred to. That work is still ongoing. It's still preliminary, what we have reported so far. So as we learn more, we will inform.

Our next question comes from Mani Foroohar at Leerink.

How do we think about when we're going to get more data on further follow-up from this cohort, including your own investigation into potential drivers of the differential CR rate? And secondarily, on what time horizon do you expect to see a little bit more information on the impact of surfactant bladder wash?

Yes. So thanks, Mani, for the question. As we said before, this is a preliminary data cut. The data is still immature. We'll be waiting for the data to fully mature. We expect that in the second half of this year. And we'll update the market once that data is available. As it relates to the surfactant bladder wash, this is a concept that we've been working on for many years. We're pretty excited about the potential of a simple bladder wash. It's taking some time to actually select the right bladder wash. But we're really pleased to be up and going with 20 sites, screening is occurring. And so once we have a better handle on where we are with enrollment, we'll then update the market as to when we expect data.

Okay. That's helpful. And as a quick follow-up, on Maury's earlier question around engagement with the FDA, would it be reasonable for us to expect a further update from you guys on timing of your ongoing engagement with the agency? Or is that something that wouldn't happen until after a fulsome and complete data from LEGEND later on this year?

Yes. I think the better way to think about it is after we've completed the LEGEND pivotal cohort, that's when we'll be able to give more color on that.

Our next question comes from Jeff Stith at Wells Fargo.

This is Jeff on for Yanan. So just thinking about approvability based on precedent. So the Adstiladrin trial I don't think allowed re-induction. So is a 12-month CR rate of 25% in the trial with re-induction in the protocol sufficient? Have you had that type of conversation with the FDA in the past?

Well, I'm not sure I'm tracking 100% here, Jeff. But the reality of it is these products are all sort of individual approaches. We have an individual discussion with the FDA. They know that our therapy is a different therapy, right? So when you think about re-induction, some products, there's an intense period, and then you re-induce. Our medicine is almost like a continuous medicine, like every quarter for a year. And that is actually similar to [ Instillagel ], right? So I think we feel pretty comfortable that our trial approach, how we provide the medicine to patients is in concert with what the FDA expects.

Okay. And then, did you analyze the any time and 6-month CR rate for the pre and post patients, similar to what you did in the November readout? Or will you share that at AUA?

So what we analyzed is ultimately, as a result now that we have presented the totality of the data, we look specifically at the last batch of patients and where we saw the lower CR rates. But now if you look at the results, the difference between the pre- and post-amendment, as we have presented back in November last year, is no longer as significant because the complete post-amendment population is no longer a population of 62 patients, but now 94 patients that includes the last batch of patients. So that difference is no longer as significant as we had initially seen, which was, as you know, based on smaller sample sizes as well.

Our next question comes from Allison Bratzel at Piper Sandler.

One for me on safety. Could you just expand on the Grade 3 and higher treatment-related AEs you observed? I think one of the footnotes talked about a Grade 4 ALT elevation. So just wondering if you could expand on that? And then secondarily, Ron, I think I heard you say that fewer patients elected to undergo re-induction in this latest data cut. Could you just expand on that? And do you have any sense why that is and if that explains much of the difference compared to the October data cut?

Yes. So Ally, thanks for those questions. Let me take the second question first, and then Hussein, you can take the first question. So the way that, that detalimogene is administered, after 3 months, if you are a CR or a non-CR, you're supposed to be dosed at the 6-month time frame. So obviously, those patients that are CRs that get dosed at the 6-month time frame can go on from there. If you are a non-CR, they -- you are supposed to, according to protocol, be re-dosed, right? But we can't force patients to do that, right? And so there were a number of patients who elected to leave the study instead. And that is a protocol -- that is against the protocol, and so we would have preferred that they continued on. But again, this is subject to what people want to do, and so we can't control that. And Hussein, for the first question?

Yes. In terms of the Grade 3 treatment-related adverse events, we had a total of 6, which is out of 125 patients. So about 5% of patients had Grade 3 TRAEs. Of these, only 1 had a Grade 4 TRAE, which, as you mentioned, was the elevated ALT, which is a liver enzyme. As you may know, treatment-related adverse event is a subjective assessment provided by the investigator based on what they think. Oftentimes, there could be lab abnormality. Ultimately, this is a lab abnormality, which the investigator associated thought it could potentially be because of detalimogene. We, as a sponsor, do not necessarily believe this is the case, but obviously, we reflect the data as the investigator has entered in the database. So it may change down the line if the investigator changes their assessment. But what we can say is that it has resolved, and it did not lead to discontinuation. And so we feel very confident about the safety profile of detalimogene, and we don't think that these limited Grade 3 TRAEs are problematic.

Our next question comes from Michael Schmidt at Guggenheim.

Maybe just going back to the regulatory question. I think it sounds like there's obviously a recent precedent and strong belief that the single-arm study regulatory path is still open for NMIBC. But what about the efficacy bar? When I look at recent approvals, studies, single-arm studies were designed to exclude a 20% CR rate with the lower bound of the 95% confidence interval, which you obviously clear in the study. And so far -- and my question is, do you think that CR bar is still applicable today given that there has been new approvals in the space? And how should we think about the bar for duration of response from a regulatory perspective?

Thanks for the questions, Michael. I don't want to speak for the FDA, right? However, let's think about how the FDA thinks about these things. So first of all, they think about these submissions in unique discrete data sets, right? So it's manufacturer by manufacturer. Detalimogene is the only nonviral approach that is being developed for this space. The first responsibility for the FDA is around safety, right? And I think that -- I think we've demonstrated a pretty compelling safety profile with detalimogene. And you see that manifested in the very low rates of treatment discontinuations and the very low rates of treatment interruption. So that's the first hurdle. The second hurdle is in regards to efficacy. And there, again, the FDA does not give you any efficacy bars. And again, it's in the context of this filing and not in others. I shared with you some data that shows that we are in line at this time frame with other approved agents. And in fact, this will change over time, right, as we finish the study. And the third thing that the FDA looks at is at manufacturing, right? And from a manufacturing perspective, can you do this consistently? Is the product safe? How is it handled, et cetera, et cetera. And as I indicated earlier, we've completed our PPQ batches or the FDA validation batches. We've had a good dialogue with the FDA, so we feel pretty good about that. So it would be inappropriate for me to speculate about the FDA in terms of approvability. But I think, hopefully, I've given you some context, and we will have a dialogue with them later this year.

Okay. And then maybe just following up on your sort of market research work. If approved, obviously, with this profile and all the features of the product, how do you think this could slot into the treatment paradigm relative to other available therapies in NMIBC?

Thank you for that question. So I think the market research and our survey data have indicated that urologists managing the most number of patients have the fewest resources. And in general, we've seen low uptake of new therapies with these urologists, but we know they'd like to incorporate novel therapies into their practice. And I think given detalimogene's ease of use, tolerability, our low rate of progression seen to date, it could be a useful tool in their kit with which to offer a bladder-sparing option to patients. And as detalimogene offers the urologists the opportunity to offer a bladder-sparing option, they will know how quickly it works. And given the tolerability profile and the low risk of progression we've seen to date, it should have a minimal negative impact on patients. And we believe it slides easily into practice flow without consuming those additional resources. So we believe there's a place for detalimogene.

Our next question comes from Judah Frommer at Morgan Stanley.

This is Nick on for Judah. Can you hear me okay?

We can hear you perfectly, Nick. Thank you for joining us.

Just on the protocol amendments. We've talked a bit about the re-induction data, but can you help us with any potential impacts you might be seeing from the other amendments? Did you see any positive effect from that requirement to get a biopsy confirmation before discontinuation? Apologies if I missed that in the prepared remarks.

No worries. So maybe going back to the protocol amendment. Ultimately, back in November, this was a hypothesis that we felt could justify and explain reasonably, why we were seeing a difference between the pre-amendment population and the post-amendment population based on the smaller sample size and limited follow-up that we presented back in November. But as mentioned, now that we have a larger database with more patients and longer follow-up, those differences between the pre-amendment and post-amendment are marginal. We don't know as of now, what the reason is for the difference in that last batch of patients. But in the totality, that difference has not materialized as we had initially anticipated. That being said, we do believe that the changes that were made in that protocol amendment were clinically relevant. They are supposed to improve and they have improved the patient selection to make sure that they are aligned with the AUA guidelines. But have we seen that difference based on the comparison of pre- and post-amendment? At this point, based on the totality of the data that we have, we're not seeing that. I mentioned also before, we're still at the beginning of this activity, and we will be conducting further and more detailed analysis, and we'll update you once we have more information.

That's helpful. Maybe just one more on the stats plan. I think you had planned to engage with the FDA on which patients might be included in the final efficacy evaluable population. Can you just share latest thinking on that? Did kind of the latest data change anything in that regard?

Yes, Nick, I'll take that question. Look, when you are -- fully enroll a study, it's normal to start engaging with the FDA on our statistical analysis plan. This is a back-and-forth process. So we have submitted our proposal to them, and they will come back with us with something. We will do sensitivity in subgroups. So it's a dynamic process. I think at the end, though, we will expect a number of patients to be censored from the 125. We do not know what that is, as yet. So that will change the denominator and will have an impact on our efficacy rates.

Our next question comes from Sean McCutcheon at Raymond James.

Can you speak to the conversion rate from 3 to 6 months and whether you think perhaps a higher dosing intensity similar to what we've seen for other programs and a true re-induction versus continued therapy would have made a difference? And could you provide any commentary on proportion of T1 patients in the population enrolled post October 2025?

So from a re-induction rate perspective, as mentioned, we saw that 6 patients were successfully re-induced. If you compare this with what we have disclosed back in November, we had 4 patients that were successfully re-induced. So in total, the number -- the total number of patients that were successfully re-induced is at 14%, which is lower than what we had originally anticipated. Now as to what the reason for this is, we are yet to analyze and study this further. But for sure, and this is independent of this outcome, we have constantly been working on continuous improvement of detalimogene and finding ways to make this product even more attractive. And this includes the surfactant bladder rinse, which, as I've shown in the preclinical data, introducing the bladder rinse does increase the transfection efficiency and the expression of IL-12. So we do believe that this could be a very attractive addition to detalimogene that could improve the efficacy as a result of the surfactant addition. So more to learn about this, but we believe we have potential things that could optimize detalimogene further.

Our next question comes from Chiara Montironi at Kempen. Chiara, you might be on mute?

Sorry, here I am. I have two, if I may. So the first one is how much the pre-amendment data weighted on the durability metrics that you are reporting? So basically, how many of these patients with long-term assessment derived from the pre-protocol amendment cohorts? And the second one is around time lines for the BLA. So how does the surfactant study -- how should we expect that the surfactant study will impact the time lines for the BLA?

Thanks, Chiara, for joining us. Let me take that second question first, and Hussein will take the first question. The surfactant bladder studies are independent of the BLA filing. So our plans are to complete Cohort 1 -- mature -- today, this is a preliminary look at the data. There's still much more data to come over time. So mature the data and have a discussion around filing detalimogene on the basis of Cohort 1. We would see the surfactant bladder rinse work as more of a life cycle management opportunity. We're pretty excited. We think that looking at our preclinical models, that this can help to boost efficacy, but also you make it even more convenient for the patients and for the practice. So we're looking forward to enrolling that study and sharing that data with you at a later time. Hussein?

So to answer your question, Chiara, on durability, I think the first thing is just to emphasize that the durability data that we have so far is still preliminary. And this is also reflected in the confidence interval that we shared for the Kaplan-Meier estimate, which has an upper boundary that goes into 40%, approximately. The other piece to compare between the pre-amendment and post-amendment patients, obviously, the pre-amendment population, which -- the amendment was from 2024, that data is mature. And as we have disclosed back in November of last year, those patients, from a durability perspective, did not perform as we had hoped with a 12-month CR rate, which were lower than those of approved products. That being said, the -- we still, at this point, if we look at the totality of the data, we have about 21 patients where -- that are still ongoing. 19 of these 21 patients have a CR at 9 months or at 6 months and are still pending their next assessment. And we also have 2 patients who are being re-induced and are pending their 6-month assessment. So the longer-term durability for the post-amendment population is still preliminary and still outstanding, and there is more to learn about this. And we look forward to seeing that data that will further characterize the efficacy and durability results of detalimogene.

If I can just ask for more clarity. So the data that you're reporting on durability will be together, right? Both pre and post together?

That is correct. Given Hussein's comments, now that the post-amendment patients are so much larger than the pre-amendment, they now represent a smaller population. We're now at a point where we put them all together.

Our next question comes from Andres Maldonado at H.C. Wainwright.

Just two quick ones from us. Ron, you had commented that the use of a surfactant was always kind of something that you guys had thought about. So can you just talk a little bit more about the historical data that supported perhaps the initial decision to move forward without a surfactant rinse? And I guess in that same regard, would you expect there to be a more amenable maybe tumor morphology or certain type of tumor geometry that would be more susceptible to this surfactant treatment versus -- so comment on if it's more effective in CIS given that it's on the surface versus Ta versus T1? And then a secondary just side note, it would be great if you guys could talk about a little bit more beyond the baseline differences you are assessing in terms of -- outside of the basic demographics, is there any other kind of demographic that could really drive the narrative here about why the data kind of has such a large delta? I mean, could you -- can the data gap be closed by having -- looking into site-level effects, maybe unique urine cytology, some kind of inflammatory markers?

All right. Well, thank you for those questions, Andres. We're going to have to put you on the team with us to help us with this data analysis. So first of all, to your questions around the surfactant bladder rinse, right? So the original design principle for detalimogene was to have the simplest product for both urologists and patients. And based on our Phase I data, I think we felt pretty good about where our efficacy and tolerability sat. But we always, always intend to think of ways we can make detalimogene even more efficacious and convenient. So while we were conducting the Phase I portion of LEGEND, preclinical work evaluating various surfactant bladder rinses was initiated. And frankly, we and our advisers became excited by the potential of drastically reducing the dwell time and thereby improving the patient and practice experience. So a number of different surfactant rinses were evaluated, and that took some time prior to selecting polidocanol. So hopefully, that gives you a little bit of color. And to your second question -- and I'm teasing you a little bit, Andres -- but that's exactly what we're doing. So the examples that you were giving, we're now -- the data is still pretty fresh. We had a preliminary look at things, all the things that you talked about and more, what we're going to dig into in the coming period.

Our next question comes from Silvan Tuerkcan at JMP.

Maybe just kind of along the similar line of questioning here, but maybe around the statistics of the data that you presented today. So those Kaplan-Meier estimates, obviously, there's a big focus on 12 months here. But I guess they are blended from -- we got those pre-protocol patients that kind of weigh on the tail, maybe pull it down. And then the important post-protocol patients that kind of split in this group that respond and didn't respond, a lot of them in the 6 months. So at the 6 months rate, like what -- did you do any back-of-the-envelope calculations on what are the odds are that the difference in the 6-month rate between the cut in the post-protocol that we've seen before and that we are seeing after the cutoff is significantly lower, one that's noise versus some systemic issue that went on at the sites?

Thanks, Silvan. No, we have not done that, and that's part of the work that's ongoing. Like I said, the data just recently cut, right? And so now our teams are really digging into all those questions that you just articulated.

And the bladder, the rinse, these 80 new patients, would any of those be available for the next data cut? Or is that still very early?

Yes. It's hard for us to say. I'm actually really proud of the team. We have 20 sites up and going, and sites are coming on board. There's a lot of interest within the community. And so we have to see how screening and enrollment goes before we have a sense of what data we'll have at what time, but we're looking forward to providing you an update on that.

Yes. Thanks, Silvan, for the questions. So this concludes today's Q&A session. I'll now turn it back over to you, Ron, for closing remarks.

Great. Thank you very much, operator. As I said earlier, the emerging profile of detalimogene is starting to become clearer. And so let's take it from the perspective of a busy community urologist. So the first challenge facing the urologist is to convince, usually an older man in their 70s on other medications with comorbidities, that after BCG failure, to use another medicine. Detalimogene's tolerability profile and lower number of administrations are attractive. Next, the urologist will want to know quickly if the product is working. And if it doesn't work, do they have other options? With a rapid onset of efficacy, over 90% of the responders getting in effect within the first 90 days, and a very low rate of progression to muscle-invasive or more advanced diseases are attractive characteristics of detalimogene. The next challenge is to convince the practice administrator to be able to use a higher cost medication. With regular refrigeration and freezer storage, no need for special equipment or personnel and the possibility of implementing buy-and-bill, detalimogene is attractive. We believe there is a unique position for detalimogene for community urologists. Thanks again for joining the call. We look forward to keeping you all updated.