enGene Holdings Inc. (ENGN) Earnings Call Transcript & Summary

Greetings, and welcome to enGene's conference call to discuss the company's preliminary LEGEND data. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce Lauren Hopfer, enGene's Executive Director of Investor Relations. You may begin.

Thank you. Good morning, everyone, and thank you for joining our conference call to discuss enGene's preliminary data from LEGEND study's pivotal cohort of patients with high-risk BCG unresponsive non-muscle invasive bladder cancer with carcinoma in situ, or CIS. The company recently posted a slide deck on its website, which we will refer to during this call. The slides are available on the Investors section of our website. Before I begin, I would like to remind you that during our prepared remarks and Q&A session to follow, we may make forward-looking statements for purposes of U.S. and Canadian securities laws. These statements include, but are not limited to, our current expectations regarding the potential benefits of the amended protocol for Legend, the potential benefits of detalimogene, timing of clinical data, timing of regulatory submission and prospects for regulatory approval on detalimogene. They involve risks, uncertainties and assumptions that are difficult to predict and may not prove to be accurate. Actual 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?

Thank you, Lauren, and thank you, everyone, for joining our call this morning for an update on the pivotal cohort of the detalimogene LEGEND study. Before I introduce the other speakers on today's call, and we share our preliminary data, I just want to take a moment to say how excited we are as an organization to have made so much progress in our efforts to bring detalimogene one step closer to providing patients living with NMIBC a new bladder sparing therapeutic option. This is a true team effort across all functions, and I couldn't be more proud of the team. We are pleased to announce completion of enrollment in the LEGEND pivotal cohort, enrolling 125 patients, which is 25% above our original target driven by investigator demand. I'd like to point out as well that to our knowledge, this is the largest pivotal cohort in NMIBC. As a reminder, in September of last year, we provided a LEGEND data update that felt the protocol was not optimized to demonstrate detalimogene's efficacy as the patients enrolled were not managed consistently per standard of care. As a result, several important protocol changes were implemented in the fourth quarter of last year. We're delighted to report that the protocol amendment, along with excellent execution made a significant impact and increased the complete response rate at 6 months to 62%, which is notably greater than what we previously reported. The 6-month CR rate seen in amended protocol patients is competitive with other novel therapies for BCG unresponsive NMIBC. With an evolving competitive efficacy profile and trending towards what we believe to be best-in-class ease-of-use handling and tolerability, our novel investigational nonviral gene therapy has the potential to be a highly differentiated therapy and the first choice therapy in the treatment of NMIBC. Now I'd like to take a moment to introduce additional speakers joining us on today's call. First, Dr. Hussein Sweiti, enGene's new Chief Medical Officer. Dr. Sweiti joined us in September from Johnson & Johnson. He most recently served as Global Medical Head, Oncology Clinical Development and led end-to-end clinical strategy and execution for the company's bladder cancer portfolio, culminating in their approval of Inlexzo. Dr. Sweiti has quickly made a positive impact, and we're thrilled to have him here at enGene. I'm also very pleased to have with us today Dr. Suzanne Merrill, Senior physician, Urologic Oncologists and Bladder Cancer Regional Lead at Colorado Urology, a large community-based LUGPA or Large Urology Group Practice Association. Dr. Merrill is a Board-certified urologist who is fellowship trained in urologic oncology. Dr. Merrill will share insights into her community practice setting, management of NMIBC patients and the emerging detalimogene data. Welcome, and thank you for joining us today, Dr. Merrill. I'll now turn the call over to Dr. Sweiti to walk you through our data. Hussein?

Thanks, Ron, and thanks, everyone, for joining. Before I dive into the data, I want to say this is an exciting time at enGene, and I'm very happy to have joined the company to advance the clinical development of detalimogene and our DDX platform more broadly. I believe detalimogene as a nonviral gene therapy offers a highly differentiated emerging profile that has the potential to address an unmet medical need for patients with NMIBC and their providers. Starting on Slide 2. First, I'd like to ensure you are all aware of the protocol amendments that were -- that was implemented in the fourth quarter of last year. This was an important amendment as it aligned our protocol more closely with standard of care and AUA guidelines. Key changes in this amendment included: first, for patients who present with CIS plus T1 papillary disease screening, we mandated that each patient has their T1 lesions reresected prior to enrollment in our study. If T1 disease was detected after the second resection, the patient was ineligible to enter the LEGEND trial. If there was no T1 at the second resection, the patient could enter LEGEND. In addition, patients who recur with TA papillary disease at 3 months can be resected at 3 months and receive reinduction. Third, for patients with cystoscopic suspicion of persistent or recurrent CIS, biopsy confirmation is required prior to discontinuation. Previously, these patients were discontinued without pathologic confirmation. We believe these were important changes that aligned our trial with guidelines and standard of care. Now for Slide 3. Turning to LEGEND'S pivotal cohort. As Ron pointed out, we're excited that enrollment is complete with 125 patients enrolled. Importantly, the majority of patients in our pivotal cohort were enrolled recently under the most recent protocol version. Specifically, 75% of all patients, which is 94 patients were enrolled in Cohort 1 under the amended protocol, of which 62 patients have at least 1 post-baseline assessment and the remaining do not yet have efficacy results reported as of the data cutoff. 25% of all patients or 31 patients were enrolled in Cohort 1 prior to implementation of the protocol amendment, of which 21 patients were presented last year and an additional 10 patients make up the remainder. Moving to Slide 4. Now let's take a look at the patient characteristics for patients pre and post amendment. It is important to note that these characteristics are highly consistent. We're talking about a predominantly elderly male population greater than 70 years old that is heavily pretreated with BCG. Importantly, we also have a high percentage of patients with high-risk characteristics. 1/3 of patients recurred on additional therapies other than BCG and 42% of patients have concurrent papillary TA or T1 disease. These high-risk characteristics in Legend's pivotal cohort make cross-trial comparisons more difficult. On Slide 5, now let's have a closer look at our preliminary post-protocol amendment data. We are very encouraged to see that the any time CR rate is competitive at 63% Also, the 3-month CR rate is 56% and the 6-month CR rate is 62%. And I'd like to highlight a few important points. As you can see on the table, at 3 months, we had 62 evaluable patients at that time point compared to 37 evaluable patients at the 6-month time point, meaning there are 25 patients who have not received a 6-month assessment. Results from the 6-month assessment for these patients may therefore impact the any time CR rates as well as the 6-month CR rate. In addition, at the 6-month time point, we have 4 patients who were originally non-CR at 3 months and who converted to CR at 6 months following re-induction. Also, among the 23 patients with CR at 6 months, 5 reached the 9-month time point and remained in CR. 17 patients were ongoing and haven't yet completed their 9-month visit and 1 patient dropped out after the 6-month time point. So while the number of patients who were in complete response at 9 months is small due to our limited follow-up, we are encouraged by these preliminary results at this later time point in patients enrolled under the amended protocol. Turning to Slide 6. Now let's have a look at our pre-amendment data. You are all familiar with our initial data presented in September last year for 21 patients, which is outlined in the first table with a CR rate at any time of 71% and a CR rate of 47% at 6 months. As mentioned earlier, we have 10 additional patients who were enrolled prior to implementing the protocol amendment. If we include these patients, the anytime CR rate for 31 patients becomes 55% and 41% at 6 months. We believe the CR rates for these 31 patients enrolled pre-protocol amendment may not be indicative of detalimogene's potential efficacy. Now on Slide 7. Let's take a closer look at how CR rates compare for LEGEND patients pre and post protocol amendment. As highlighted here, we are very pleased with how detalimogene's efficacy profile is evolving for patients enrolled following LEGEND'S protocol amendment. We are encouraged to see results trending in the right direction with a higher anytime CR rate at 63% and a higher 6-month CR rate at 62%. A few important points. First, I'd like to point that patients from the previous protocol version had a markedly lower 12-month CR rate than in the approved products for BCG unresponsive NMIBC. Second, it is important to note that these are preliminary data from 2 subsets of patients in the same cohort. It is likely that they will not represent the final patient number, which will be subject to the FDA's review and interpretation. In the meantime, we plan to engage the FDA to gain agreement on a statistical analysis plan and based on our initial discussions, we expect that a number of pre-protocol amendment patients may be excluded. Finally, I want to point that following FDA interaction, our primary endpoint changed from CR rate at 12 months to CR rate at any time, which is consistent with other approved products in this space. Turning to Slide 8. Finally, putting our preliminary data side-by-side with novel products and acknowledging the limitations of cross-trial comparisons and the caveats provided to you earlier, including the high-risk characteristics of patients enrolled in our pivotal cohort. We believe that our 63% CR rate at any time is within range of recently approved products. We also believe our 62% 6-month CR rate in the post amendment population is trending competitively. Taken together, our preliminary efficacy, ease of use and attractive tolerability profile, which we'll discuss momentarily, delivers what we feel is a compelling product profile for both physicians and patients. Moving to Slide 9. Looking ahead to our next potential data update, I want to recognize that enrollment was heavily skewed to the last 10 months. As you can see from the plot, our enrollment rate in 2025 was more than 4x higher than in 2024. So we expect a bolus of 12-month data to become available towards the second half of 2026. Now let's turn to Slide 10. Moving to our safety data, which, as you can see, is inclusive of all 125 patients enrolled in LEGEND pivotal Cohort 1. We are very pleased with the tolerability profile of detalimogene to date with 42% of patients experiencing a treatment-related adverse events, most of which were mild, grade 1 or 2, reversible and consistent with catheterization. The most commonly reported terms were fatigue, dysuria, bladder spasm, urgency and pollakiuria. Three patients experienced a Grade III events, 2 urinary tract infections and 1 patient experienced pyelonephritis. These are common occurrences related to catheterization and instrumentation and consistent with other intravesically administered therapies. The very low rates of treatment discontinuation or interruption due to treatment-related adverse events of 0.8% and 1.6%, respectively, means that very few patients discontinued or skipped detalimogene therapy, which speaks in favor of our safety profile. Now on Slide 11. When looking across the various products approved for BCG unresponsive NMIBC, we believe the emerging tolerability profile for detalimogene is a point of differentiation and trending towards best-in-class. And I'd like to take a moment to emphasize that tolerability is very relevant for this patient population specifically. This is not only an elderly male population with significant comorbidities in the significant prior BCG treatment but also a patient population with early-stage localized non-metastatic disease. Therefore, the willingness to tolerate highly toxic therapies is low and the desire to maintain quality of life is high. Now on Slide 12. Briefly, before I turn the call over to Dr. Merrill, I want to provide a quick enrollment update for LEGEND's additional cohorts. We have enrolled 30 patients in our high-risk BCG-naive Cohort 2A. 45 patients have been enrolled in high-risk BCG-exposed Cohort 2b and 36 patients with papillary-only BCG unresponsive NMIBC have been enrolled in Cohort 3. We look forward to providing an update on these cohorts in the future. Lastly, on Slide 13. In summary, we believe that the preliminary data from patients enrolled post protocol amendment suggests the amendment appears to positively impact 6 months complete response rates. Second, we continue to see a highly favorable tolerability profile, which is very relevant for this patient population. Third, the final number of patients in Cohort 1 will be subject to FDA review as well as agreement on a statistical analysis plan, or SAP. Finally, with enrollment heavily weighted to post-amendment patients and with our enrollment curve heavily skewed to the last few quarters, we don't anticipate a meaningful amount of longer-term durability data until the second half of next year. We expect to provide a data update when we have both feedback from the FDA on our SAP and the meaningful number of patients with long-term data. With that, I'd like to turn the call over to Dr. Merrill. Suzanne?

Thank you, Hussein. It's a pleasure to be with you today. I'd like to take this opportunity to tell you a little bit more about my practice setting, the current and real-world management of non-muscle invasive bladder cancer and then my perspective on the evolving treatment landscape. Colorado Urology is a large group practice in Denver. My group has multiple practice sites across our nation and employs over 220 providers. In my region, we have a total of 25 urologists and 20 advanced practice providers and over 11 offices. Many such large practices have provider champions for specific urologic disease states, and I lead our Colorado bladder cancer program. High-risk non-muscle invasive bladder cancer patients are usually males who are diagnosed in their mid-70s and at the time of diagnosis are normally treated with the standard of care, which is BCG. When these patients progress to BCG unresponsive disease or become intolerant to BCG, they fall into a category of disease for which there are currently few options and one of which is extreme, which is to remove their bladder, a procedure called radical cystectomy. While radical cystectomy has a 100% complete response rate, there is significant mortality and morbidity associated with up to a 10% chance of death within 90 days and a substantial long-term impact to their overall quality of life. Beyond these negative impacts to the patient, radical cystectomy has significant implications on our practice as high complication rates and long-term postsurgical care needs can increase practice burden and occupy significant provider and staff resources. Thankfully, FDA's guidance for development of new bladder-sparing treatment options has increased the number of approved products and products in development for use in the BCG unresponsive setting, including detalimogene. As a result, a treatment paradigm shift is actively underway and providers such as me, are now thinking in terms of developing long-term bladder-sparing treatment strategies as we look to sequence patients through multiple intravesical therapies with the goal of providing good urologic and overall quality of life. Drug selection is a long-term strategy individualized to the patient to optimize outcomes and practice logistics. For large community urology practices like mine, we will prioritize use of an agent based on its efficacy, ease of administration, safety to patient and practice staff, drug availability and reimbursement factors. These are the choice drivers that make the difference to our patients and to us. In addition to BCG, I have had the opportunity to use Keytruda, Adstiladrin, AnNtiva and the recently approved Inlexzo. All these agents have a place in the sequencing strategy to optimize long-term outcomes. But at the same time, each of these agents pose a significant logistical challenge to efficiently administer the product. I am very pleased to see detalimogene's emerging profile to date. We are seeing competitive efficacy in patients under the amended protocol with CR any time of 63% and a 62% complete response rate at 6 months, which is in line with other novel agents. Additionally, the low incidence of treatment-related adverse events to date may be appealing to patients, many of whom have beaten up bladders, which make tolerability of the utmost importance. In addition, detalimogene's dosing frequency on weeks 1, 2, 5 and 6 for each cycle is also a positive attribute. Many patients on other therapies may have to commit to up to 12 weeks of therapy. With visits often lasting 2 or more hours compared to just 1 hour or less for detalimogene, the overall decrease in a patient's burden is also important when making treatment decisions. When looking at approved and investigational viral therapies, many high-volume practices do not have certain specialized equipment such as a biosafety level 2 hood required to appropriately handle these agents. Agents requiring additional infrastructure investment and operational changes have challenging reimbursement processes or issues with product availability will likely be reserved as last line or even not adopted at all. As a busy community practice, we try to maximize patient throughput and find it attractive that detalimogene has a favorable and familiar administration process. It does not carry complex or time-consuming logistics, add to the administration burden of complex scheduling and just-in-time shipping for patient visits or require long viral thaws, pre-installment bladder washes or post-procedural cleanup procedures. I'm very excited about detalimogene and assuming that it goes on to be approved, it has the potential to be one of the first, if not the first, intravesical therapy used in our practice to treat BCG unresponsive NMIBC. Now let me turn the call back over to Ron.

Thank you, Dr. Sweiti and Merrill. Dr. Merrill, detalimogene was very much designed with busy practices such as yours in mind. So let me summarize today's discussion with a perspective on what we know and what we don't know. What we know, non-muscle invasive bladder cancer, NMIBC, is a serious, highly recurrent but slow progressing disease that requires distinctly different treatment considerations compared to metastatic disease. Most NMIBC patients are treated by community urologists whose decisions extend beyond efficacy to include tolerability, practical fit within their workflow and the economic impact on the practice. Recent protocol amendments have improved the 6-month complete response rate and strengthened our competitive profile. Product tolerability is an important choice driver for patients and physicians. The low 2% treatment interruption rate with detalimogene suggests a very competitive profile. Nonviral gene therapies are easier and less expensive to manufacture. Detalimogene's FDA validation lots are nearly complete and drafting of the manufacturing FDA module will begin soon. Durability for the pre-protocol amendment patients is below the FDA-approved products. Heavier enrollment in the last months of Cohort 1 delays insights into durability under our current protocol. On the other hand, there are several variables that are yet to be determined, specifically, which patients the FDA will ultimately include in the final efficacy analysis of our pivotal cohort. In recent discussions with the FDA, they have indicated that a number of patients from the pre-protocol amendment group will not be included in the final analysis and that this will be resolved in the SAP dialogue. Therefore, we do not want to share 12-month CR rates from our pre-amendment population as they may not be indicative of detalimogene's potential efficacy profile and because the comparison with our post-amendment population is not yet possible given the limited follow-up. Our current expectation is that more mature follow-up, including 12-month data in our post-protocol amendment population will be available in the second half of 2026. Thank you all for attending today's call. This is an exciting time for enGene. We believe that detalimogene has an emerging competitive efficacy profile and the potential to have best-in-class tolerability and become the easiest product to use for physicians and patients. With cash into 2027, based on our latest update, we have sufficient resources to get us past the long-term data update post SAP finalization sometime in the second half of 2026 and our planned BLA filing in the second half of 2026. At enGene, it's all about bladder cancer patients, and we're excited about the potential of providing a new solution with a potential approval decision in 2027. The 3 of us are joined by Ryan Daws, our CFO. We'll now open up the call for your questions.

[Operator Instructions] The first question will come from Yanan Zhu with Wells Fargo Securities.

Congrats on the data. Maybe a question for the company and a question for the doctor on the call. For the company, can you talk about what drove the difference between the 6-month response rate, the notable increase? It looks like the 3-month response rate are similar between the pre-protocol and post-protocol amendment cohorts but the 6-month response rate is higher. If you can talk about, which of the protocol amendment contributed -- drove that change and whether -- what kind of different patient baseline characteristics might have contributed to the change, that would be great. For the doctor, obviously, the easy-to-use profile of detalimogene, you are already well aware of. Given that profile, what is the ultimate efficacy profile does detalimogene have to demonstrate for it to be used on a regular basis in your office? Obviously, the data is not mature yet. So in your mind, for the final data profile in terms of anytime response or 12-month duration response or landmark 12-month response, could you state any bar given the easy-to-use profile?

All right. Well, thank you, Yanan, for the questions and for the kind words. We're pretty excited to show the detalimogene demonstrated the improved CR rate at the 6-month time frame of the post-protocol amendments. Let me have Hussein answer your first question, and then we'll turn it over to Dr. Merrill. So over to you.

Yes. Thank you, Ron, and thank you, Yanan. I think, first of all, I just want to acknowledge that we're talking about overall the small sample size and the preprotocol amendments as well as in the post-protocol amendment that is informing the 6-month CR rate. I think we obviously are very excited that to see an improvement in the 6-month CR rate, and we believe that the protocol amendment, along with very strong execution by our team is contributing to these improved results. And we look forward to analyzing the data further. But overall, we're talking still about early preliminary results that we look forward to follow on with more updated results in the second half of next year.

All right. This is Dr. Suzanne Merrill. Thank you for that question. I would say probably the most impactful endpoint to us, physicians is going to be durability of response. So the 6-month complete response rate, which is trending competitively for detalimogene is very promising. However, I will say, once all these products get FDA approved and are available to us providers and practices, and they're all really looking the same in regards, again, showing a kind of equally competitive efficacy, what we're going to end up reaching for, for our patients, especially when looking at what we call the long-term game for bladder-sparing therapies in these patients is really going to focus on those key components of tolerability of use for the patient, ease of administration from the practice standpoint and safety for our staff. And so if it fits -- if the drug fits the bill that it really doesn't have to change our operations, it's tolerable to the patients who right now at this stage of their disease are having a number of baseline bladder symptoms are older, more frail, they want to deescalate care themselves. We're going to gravitate to a product that fits all those aspects. And detalimogene right now is showing to be very promising in fitting all those aspects compared to what products are on the market currently.

And then the next question will come from Judah Frommer with Morgan Stanley.

Congrats on the update here, guys. Maybe just first for the company. Can you help us a bit more with planned interactions with FDA, what you'll be waiting to hear from them in terms of number of patients that will be acceptable for the SPA? Is it possible you'll have to enroll additional patients? And then for Dr. Merrill, just curious from your perspective and your colleagues' perspective on awareness of detalimogene versus maybe Inlexzo and the CG Oncology product, what is the level of awareness that there is a potential nonviral gene therapy coming? And what potential usability would be with the profile that's being accumulated here?

Judah, thanks for joining us, and thanks for the question. So first of all, the detalimogene pivotal cohort is actually the largest database that we are aware of. And so as a result, we don't anticipate the need to enroll any additional patients given the size of it. Now our interactions with the FDA fall under our RMAT designation. So we're delighted to have that designation allows us to have a closer relationship with the FDA and better dialogue. Like all companies that are finishing up the pivotal program, we'll be having a discussion on the statistical analysis plan, or SAP, and that's pretty important. And in that, we will go back and forth with the FDA and dialogue about which patients we believe are the efficacy evaluable patients and which patients will not be. And we'll go back and forth. As I said, that's a standard process. But we anticipate that of the 125 patients that we have, like other companies, a number of patients will not be included in the final analysis. And over to you, Dr. Merrill.

Thank you, and thank you for the question. So in regards to the awareness of detalimogene, I would say, ultimately, enGene has done a great job in making all of us bladder cancer leads aware of what's coming down the pipeline and updating us in regards to their trial enrollment and ultimately, when their readout is going to be we are all very in the bladder cancer space, very acutely in tune to what is coming -- what is currently available, obviously, and what is coming down the pipeline. And the reason is, is that there's just been, as you well know, so much excitement in this space that we are excited, too, to see all the innovation coming down. And so I think we will be primed and ready once detalimogene's is approved to be ready to uptake this product. And I think it will have a high uptake because it has that competitive advantage from being a nonviral therapy. This really poses a lot of advantages to provider practice and patient alike compared to what is currently available now, which right now, most are viral therapies have a particular difficult administration and scheduling process for our patients. And then with the most recent product approved Inlexzo, the operations are very different. Most of us in practice use our medical assistance to administer these products. So we, as providers can see other patients alongside of our patient being administered the bladder cancer therapy. Inlexzo requires us providers to be in that room, both administering and retrieving that product. And it will be some time before we can even maybe hand that down to our advanced practice providers to do that job. But it will never likely become a medical assistant product, which for us operationally is very challenging to handle. So again, detalimogene, I think, has a number of competitive advantages from being nonviral and having that great tolerability also to our patients. But first and foremost, it will not change our logistics of our practice.

And the next question will come from Sean McCutcheon with Raymond James.

Congrats on the data. A couple of questions from us. Maybe first, can you speak a bit more to the baseline disposition of these patients, particularly post-protocol changes on the proportion of Ta, T1 relative to parallel trials and how you think we should be contextualizing the results in that respect? And then secondarily, can you speak to the acceleration and pace of enrollment, the factors that drove that inflection and how you saw that flow through to the other LEGEND cohorts? And now that a substantial number of patients are enrolled in those cohorts, how are you thinking about cadence of disclosure there?

Sean, thanks for the kind words and for the question. Let me take the second question first, and Hussein can take the first one. Look, in general, these studies tend to have a hockey stick approach to things as you get sites up and going. I think in our case, 4x the enrollment in the last period is probably a little bit steeper. I think it has a lot to do with Hussein and our clinical operations team, I just think better execution overall. And quite frankly, as Dr. Merrill has indicated, as doctors started to understand more about detalimogene, the excitement started to build. So actually, it was pretty tough to close things off. So we're pretty excited about exceeding our original enrollment target, and we look forward to the data maturing. And Hussein for the other question.

Yes. Thank you, Ron, and thank you, Sean. In terms of the patient characteristics, I think overall, the pre- and post- amendment population have consistent characteristics, which is a very good sign. Also, this is the patient population we'd be expecting to enroll in a trial like LEGEND with -- in terms of patients who are predominantly male, predominantly elderly, greater than 70 years old, heavily pretreated with BCG. And I think the 2 aspects, which struck me in terms of this patient population is that there are -- there's a very high percentage of patients with high-risk characteristics. And I'm speaking specifically about the proportion of patients who do not have just pure CIS, but also have CIS along with capillary disease, Ta or T1. We're talking about 42%, which is a high proportion as well as 1/3 of patients having been previously treated, not only with BCG but also with other intravesical therapies. And together, this means that this is a high risk -- a very high-risk patient population, generally difficult to treat. So seeing the efficacy results that we have presented so far is very encouraging to us given the high-risk characteristics of this patient population.

And I think, Sean, I think it's our understanding that those numbers that Hussein shared with you are higher than that of some of the other products. So it really is a population that is representative of NMIBC patients, but probably a little bit on the higher side of risk. So therefore, the numbers that we're showing actually get us very excited.

And the next question will come from Mani Foroohar with Leerink.

Congrats on the data. I guess this is a little bit of a repetitive question but I wanted to dive in for the clinicians on the call. When we think about these agents, obviously, they're not entirely apples-to-apples. There's subtle nuances in the patient populations as will always be true with the heterogeneous illness. How do you think about, which patients should be used -- which agents should be used for which patients first? And what are the key metrics in making those decisions in terms of efficacy, safety, et cetera? I'm presuming that no practice is going to use 100% of one product or another. So how does one slice up the pie of one patient population?

Yes. Before I hand it over to Dr. Merrill, I think just one of the perspectives that we have, Mani, and thanks for the question, is that given the emerging 12-month rates for these products, that sequencing will be the order of the day. And so the market should grow overall. And maybe Dr. Merrill, you can kind of talk a little bit about your views and how you might think about those sequences.

Yes. Thank you. Exactly right that ultimately, when we are going to have a lot of products under one indication, BCG unresponsive CIS, plus or minus papillary disease, that it's really going to be about sequencing. And what is going to rise to the top likely is not going to be first actually efficacy. It's going to be what's going to be best for patient and practice alike. And I think, as you said, yes, that patient in front of you is going to, in part, differentiate what we use. However, in general, what is going to be very important to us providers is that; one, we're going to be able to logistically administer the drug, get the drug very easily, get that patient through the scheduling process but then nicely paired that, that drug is going to be well tolerated from that patient. A lot of these patients, when we're talking to them in the clinic, of course, do not want to escalate their care to doing cystectomy. And thankfully, now we don't have to turn to that option as readily. But they very much do want to have a therapy where their quality of life is not going to be challenged and detrimented by the therapy. And that plays in both to the tolerability of the drug as well as the, again, frequency of administration. So with all these drugs that we're going to have in front of us and the need to sequence, we're going to preferentially recommend a drug that we know is going to be tolerated well, that's going to be easy to administer, that's not going to have such frequent administration for the patient so they can be able to somewhat deescalate their care, tolerate the therapy and then, of course, that it's going to be easy for us to do upfront. And then we're going to see how these patients then play out in terms of who responds and who doesn't and then be able to ourselves again, escalate again, the logistics of our administration of these bladder-sparing therapies for only those patients that actually need for us to do so. So again, I really believe that the first therapy that the majority of us will gravitate to once all these therapies are again are on the same playing field pretty much from an efficacy standpoint is that, which is going to be tolerable to the patient, not as frequent for administration, again, and is ease of use from our standpoint, provider standpoint, from an operations standpoint.

Great. And if I can slide in one follow-up. One of the conversations that comes up frequently is around duration of response that also came up in the early days of the formation of the modern myeloma market, also an elderly population with many serial lines of therapy was on duration of response, how much time one buys with each therapy. Presumably, once this product is on the market, there will be longer-term duration of response data from some of these competitors. That's just a function of the studies being done sooner and the clock running. How do clinicians think about the duration of response data? Is that something that you -- that they compare in terms of efficacy, in terms of deciding sequencing? And how mature does that have to be to drive decisions in terms of first line versus second line use or first agent versus second agent use, I suppose?

Yes, Mani, thanks for that question. I think Dr. Merrill made some comments about that earlier. So let me just add a little bit to what Dr. Merrill said. As we start to do market research for these patients, remember, Dr. Sweiti described these patients, these are patients that are mid-70s, usually male, right? And then if you think about their potential lifespan and then with the number of agents that are going to be available, I think what we're finding from market research is that obviously, progression is an issue. But if patients recur, they have the opportunity to use other agents and cobble them along. So hopefully, the patient passes from something else other than their bladder disease. So thank you for the question.

And our next question will come from Michael Schmidt with Guggenheim.

This is Paul on for Michael. Let me add my congrats on the update today. Just had one question for me. If possible, could you share some color on what parameters the FDA is considering when deciding, which patients in the pre-protocol amended population could be included or excluded from the final analysis? I know you mentioned you've already gotten some feedback that at least some patients will not be included. So just curious on the nature of the input to date and perhaps what's the range of scenarios from the outcome from your SAP discussions?

Paul, thanks for joining us, and I appreciate the question. It's a pretty standard discussion that we will have with the FDA. Remember, when you have 125 patients and over 90 sites, there's some variability that can occur in the execution of the trial. We obviously want our investigators to keep patients between the inclusion/exclusion criteria, but things happen to patients and things happen in these sites. So that is probably where we'll be focusing with the FDA, trying to have a homogenous patient population as possible. And as you've seen with some of the products ahead of us, you'll see that their publication end are much higher than what the FDA expects. So that will be a dynamic process for us. Thanks for the question.

And the next question will come from Leland Gershell with Oppenheimer.

Great. Let me add my congratulations on the terrific data. One question for the company and then one for Dr. Merrill. Just I know, obviously, the cost of goods for detalimogene are quite favorable relative to some of the other agents. Just wondering if you could share any further color on what the GOGS may be. And then for Dr. Merrill, just curious, given the shift of the primary endpoint to anytime CR versus kind of more of a time-based landmark, just wondering how practitioners view anytime CR versus being cut at certain points.

Leland, thanks for joining us, and thanks for the questions. I think as you said, manufacturing for us is a real advantage. And you hear Dr. Merrill talk about that from a provider perspective. But from a company perspective, since it's a nonviral gene therapy and since it is readily available ingredients and since we are already manufacturing at scale, we feel very confident about being able to provide the market in a cost-effective manner. We also feel pretty good about our opportunities with the FDA. We're nearly complete our FDA validation batches. We'll be writing a module for the FDA for submission. And given that we have the RMAT designation, that also allows us better dialogue. So we feel very good about where we are from a manufacturing perspective. Over to you, Dr. Merrill.

Yes. Thank you. So in regards to this question about how us providers feel about CR at anytime versus a specific time point. I think a lot of us are more familiar with a CR at any time point. However, in practice, when we're treating that patient, just for example, when we're treating a patient with upfront BCG, especially a CIS patient, we really do not assess durability of response at 3 months because we know CIS patients actually need a longer exposure to BCG or whatever agent you're using beyond, for example, 3 months. So that's why a lot of, again, these trials and then, again, readouts from the products that are available are reporting CR at any time because patients, particularly with CIS and then, of course, with and without papillary disease do need a longer duration of response to the agent, and we can see them actually responding later on in their course of exposure to the product. So ultimately, we're more familiar with a cut point but a more accurate and more kind of all catching of what the true ability of a product, again, efficacy is, is to report that CR at any time. And I think it was, again, smart of enGene to convert over to that endpoint so we can, again, assess comparables, even though we shouldn't assess cross-trial but we all look at that. So it's nice that, that endpoint is the same. And again, it touches, again, that ability of that patient that requires that longer duration of exposure to the agent to actually show a response because that's what we do actually in practice.

And the next question will come from Silvan Tuerkcan with Citizens.

I have a couple of questions, and congrats on this great update here this morning. For Dr. Merrill, maybe from a -- I think you've highlighted a lot the operational benefit here to the clinic. But maybe just for the patient experience, can you highlight the difference in duration, maybe the dwell time or frequency of visits between detalimogene and, for example, some of these newer treatments like Cresto and Inlexzo, how that would look like? And then I have a follow-up.

Sure. Thank you for the question. So with detalimogene's being a nonviral therapy, I think a couple of important points hit home. So one, this administration is very known to this patient population via a catheter gets put in. They have to hold it just for an hour of time, which some of these therapies, we do recommend holding even for a longer period of time. This is very challenging for the patient when there is a longer, what we call dwell time in the bladder and that we have to give them extra medications to be able to quiet the bladder, hold it in, so the drug doesn't spray out or require them actually to have to stay in the clinic with a catheter clamped if they're unable to do that. So I think the decrease and amount of dwell time is important. Again, that familiarity of administration with the catheter, again, is not concerning from a patient point of view. And then with it being nonviral, there is not going to have to be all the, again, logistics from a patient standpoint of, again, flushing the toilet with Clorox. There used to be and kind of still is traditionally thought a lot of cleaner clothes afterwards, if anything gets sprayed on it. Again, a lot of challenges even in the home for the patient in terms of safety after administration of these viral therapies, and that includes, of course, BCG and also chemotherapies. And then from a staff perspective, again, with it being nonviral, a lot of the hazard precautions that we have to use in clinic for safety regulations will not have to be there either. So again, overall, really, it really fits the bill of that ease of administration.

Great. And then maybe for Dr. Sweiti, since you've worked on another recently approved agent before you joined enGene, you brought a lot of experience with you. How would you kind of characterize the interest from investigators in the current LEGEND trial versus interest doing the TAR-200 development, for example?

Yes. Thank you, Silvan, for the question. I think overall, having joined only just about 6 weeks ago, I'm very excited to be working with a very tenured experienced team, and they've done a tremendous job working with investigator overseeing the clinical trials, working hand-in-hand with investigators to make sure that the patients are being treated per protocol and they're being managed appropriately. So -- and I'm seeing a lot of excitement, and this is reflected in the enrollment that we have achieved over the past 10 months. In the presentation, I highlighted that just over the past 10 months, the vast majority of patients were enrolled and the enrollment rate was more than 4x higher than what we have seen previously. So from my interactions with investigators and key opinion leaders, it's been consistently very favorable and consistently very much happy and satisfied with the activity that they're observing with detalimogene. So hopefully, we'll continue to build upon that as we continue the LEGEND trial into next step.

And the next question will come from [indiscernible].

Team, congratulations with the update. So I wanted to have more color on the very few grade 3 events that you see versus competitors in the context of the positioning in a community setting? And then if I may, how are you thinking about detalimogene in BCG naive? How should we look at the other cohorts in the trial?

So let me just take the second question. In regards to the other cohorts, we're pretty excited about where we are from enrollment, and we continue to work through those cohorts. Obviously, the pivotal cohort has been our biggest focus. So after we finish this, we look forward to providing an update on that. Hussein, you want to talk about the...

Yes. Thank you, [ Chiara. ] So in terms of the Grade 3 treatment-related adverse events, I think we're very excited that we've had very, very few such events. I believe we reported 3 events, 2 of which were UTI urinary tract infections and one of them was the pyelonephritis. This is not unexpected in this patient population, and these adverse events can be also attributed to the catheterization or to the cystoscopy that these patients have to undergo during their surveillance or treatment process. So may not be necessarily directly associated with detalimogene. And I think what personally struck me in terms of the tolerability profile, just a very low rate of treatment interruptions due to treatment-related adverse events or treatment discontinuations. And clinically speaking, this is a very good sign that this is a very well-tolerated drug because these patients, and Dr. Merrill can comment about that, would request to discontinue a treatment or would request to interrupt the treatment if they're not tolerating it. And this is usually a sign of how well tolerated the drug is. So seeing a rate of 1% to 2% of treatment interruptions or discontinuations is very favorable from my perspective.

Operator, maybe you can help us out here with something coming into the line before we take our next question.

Give me one moment please. And our next question comes from [ David Dye ] with UBS.

I also want to add my congratulations on the data here. So a couple of questions from me. One is just on the -- for the company, any thoughts on the -- any preliminary thoughts around the pricing for detalimogene given that we've seen sort of a higher expected price for Inlexzo? And I have a follow-up after that.

David, thanks for the kind words. It's probably too early for us to really comment on pricing other than to say that I think we sit in a really advantageous position given our competitive cost of goods. And I think what we're excited about is this market is changing. And I think we will be able to really figure out what is sort of the best price to sort of optimize revenue but also optimize value for providers. So I think the big message for us is given where we are, we probably have the most flexibility in the marketplace.

Got it. Great. And this is for doctor. Just looking at the safety profile, of course, it's pretty favorable, but we just see a couple of urinary tract infections as we've seen earlier with pyelonephritis. So just curious about your view of this profile compared to other therapies like TAR-200, which does have -- seem to have higher urinary tract infections. So how should we view the overall safety profile in the context of other therapies?

In the context of other therapies, I see it as a significant advantage that we are seeing in terms of the tolerability profile of detalimogene. Again, I think these patients, we got to keep in mind, they have already been heavily pretreated with BCG. So these are beaten up bladders, as Dr. Merrill pointed out. So they have oftentimes symptoms at baseline. And just by the nature of catheterization and cystoscopy, they may experience adverse events like urinary tract infections and pyelonephritis. So we're not surprised to see a very small rate and compared to the -- to what we have observed with other therapies, overall, I think this is a very favorable tolerability profile, which we hope to build upon as we accrue more follow-up in our patient population.

And the last question will come from Andres Maldonado with H.C. Wainwright.

Congrats on the data. Two quick ones from us. So maybe one to start off for Dr. Merrill. Specifically in your practice, as we think about read-through to the other potential Legend cohorts, what is your expectation on the deltas relative to any time CR between BCG-naive or BCG-exposed populations? In your practice, have you seen with approved therapies difference in these populations, maybe even tangentially? And then maybe one last one for the company. Obviously, a lot of noise in the space. And the second kind of evolution is what we're seeing in the clinic is combinations. So with the safety profile given what you have right now, how should we be thinking about combinations moving forward there?

Well, thanks for the question, Andres. Let me take the second question first. Like it's a pretty exciting time for the physicians and for the patients to have these options. And I think over time, we do see combinations. The nice thing about detalimogene having a nonviral approach and also having a relatively low cost of goods it really becomes the perfect partner, right? So I think over time, data will suggest that the sequencing will change and combinations will change but I think we are very well positioned with the detalimogene profile. Maybe a short answer from you, Dr. Merrill, on the first question.

Sure. If we had seen a product have a good efficacy in this very kind of high-risk, highly treated population, it's our assumption and what we're kind of seeing from, again, ongoing trials is that, that same product will do very well in an early kind of stage of disease, BCG naive or BCG exposed. So I think what we reported here with a very high-risk population, 42%, again, in that BCG and responsive space showing a very competitive efficacy that we would expect great efficacy in an earlier stage of disease.

I would now like to turn the call back over to Ron for closing remarks.

Great. Well, thank you, everybody, for tuning in and sorry we ran over a little bit but we're pretty excited here at enGene because we see the detalimogene profile emerging quite nicely, competitive efficacy, competitive tolerability profile and competitive ease of use. We would not be here, though, without both our investigators and our patients, and we express a sincere amount of gratitude to them. Thank you, everybody. Have a great day.

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