EnGene Stock

All right. Good morning, everyone, and welcome to the 2026 Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the mid-cap biotech analysts here. We're very excited to have Ron Cooper from enGene kicking off the conference. Let me just read a quick research disclosure before we get started. Please visit www.morganstanley.com/researchdisclosures.

It's an important year for enGene, Ron. Before we dive in, can you give the audience a quick intro to the company and a bit of the background on your decision to pursue nonviral gene therapy?

Great. Well, first of all, Judah, thanks for the invitation to be here. Great to see you. It is a pretty exciting year for enGene. So what is enGene? enGene is a company that looked at the challenges of viral gene therapies and said, I think we can solve some of these challenges. And those challenges being packet size, redosability and the manufacturing challenge. So enGene was discovered to build nonviral gene therapies.

And then through the discovery process, translated a product called detalimogene, which is the first nonviral gene therapy that we are developing for non-muscle invasive bladder cancer. Detalimogene has been studied in the LEGEND program in Cohort 1, which is a pivotal program, 125 patients, which is one of the larger programs. And so we're hitting a pretty exciting time in the company in this next quarter, we'll have some data that will mature, some durability data that will mature. We plan to meet with the FDA. We plan to file detalimogene in the U.S. and expect a potential approval in 2027. And sitting with $266 million in cash, we're well capitalized to achieve all of those things.

Okay. Great. So like you said, you're developing detalimogene. The indication is BCG unresponsive non-muscle invasive bladder cancer with CIS. So maybe can you tell us a little bit about the burden of this disease, a little bit on the epidemiology, how many patients are diagnosed, how they're managed and really what the unmet need is that you're looking to address?

I was shocked when this opportunity presented myself. The treatment in bladder cancer actually, particularly non-muscle invasive bladder cancer is pretty poor. The definitive treatment was removal of your bladder. So the radical cystectomy. And then when I learn more about radical cystectomy, 4- to 6-hour surgery, multi-organ, 5% to 15% mortality and horrific morbidity as well, individuals landing with an ostomy, loss of sexual function. So treatment is not very good, right? Now when you think about the epi, there are about 90,000 in the U.S. in the incident population, about 90,000 individuals have bladder cancer. 80% of those are non-muscle invasive bladder cancer.

And then within that, it's estimated somewhere between 20,000 to 40,000 individuals each year have non-muscle invasive bladder cancer that is resistant to BCG. So it's a pretty significant patient population. This is the #6 cancer in the United States. So it is a relevant cancer. And the FDA put out guidance to say if you did a study about 100 patients or so open label that, in fact, you can get an approval. So we're actually at the dawn of something very special and exciting in the management of bladder cancer.

Okay. Great. So in recent years, we've gone from having very few therapeutic options to a handful, spanning different mechanisms and practice is still evolving. But what we've seen so far as to how urologists are adopting these therapies, how are they adopting kind of these newer options that are being made available to them?

Again, I think we're at the early stages of these new agents being available. And part of the challenge is when you look at the market overall, let's call it, 20% to 25% of the patients are in academic institutions. And let's call it, 75%, 80% are in the community. The newer agents, while very good, are -- come with some challenges. And they come with challenges in that they require multiple pre-washes, the intensity is very high. It requires post-treatment activity. It requires infrastructure. And they just don't -- they don't slide easily into a urology practice.

So those practices have a lot of resource. Academics have adopted them quite significantly. I would say that the community area is almost barren. So if you think about community urologists right now, what do they have? They have BCG if they can get it, right? And then they have gemcitabine, which they can use, but there's some questions about efficacy, and it's not really financially viable. And then of the new agents, gemcitabine on the pretzel may or may not be viable. So there's just not a lot of choices for these community urologists, and that's where detalimogene can really make a big difference.

Got it. So with these dynamics in mind and clearly kind of different dynamics between academic centers and community urologists, is there an estimate of how big you think the non-muscle invasive bladder cancer market could be? I think in the past, you pointed to the multiple myeloma market as maybe a relevant precedent. But what is history in that therapeutic area kind of tell you where NMIBC might be able to go?

I think it's a fantastic analogy. And I think it's something that Wall Street needs to really start to pay attention to. With the advent of new agents, what you get is patients avoiding that horrible removal of their bladder. Nobody wants to have an organ removed, right? And they will take -- our market research says right now, they'll take 3 or 4 lines of therapies at least, right? So that's a big change. So what does that do? That starts to boost the prevalent population. So let's go back to the analogy of multiple myeloma when Revlimid was launched, multiple myeloma is a $1 billion market. Right now, if you look at multiple myeloma with over a dozen new agents, a $20 billion market.

And we're now working to a point of where it's almost functional cure. What an advance for these patients. Well, I'm hoping we have the same sort of advance for patients here in bladder cancer. And right now, the agents that we have are useful, but some of them are difficult to use. But every single one of these agents, if you look at the durability of the products, they range between 40% to 50%. So what does that mean? At the end of the year, half the patients need another medicine. So medicines like detalimogene can make a really big difference there.

Okay. Great. Okay. Diving a little deeper into detalimogene. Can you tell us a little bit more about the asset, the construct and delivery vehicle? And can you touch a little bit more on your DDX platform and how it factored into detalimogene?

So detalimogene is quite simple, but quite elegant in how it's put together because actually, it starts off with a simple generic plasmid. We have 2 RIG-I genes and IL-12. Then we take -- and this is where the platform comes from. The secret sauce is our proprietary sugar DDX. They are mixed together in an in-line manner and then a proprietary PEGylation occurs to create these nanoparticles.

What's fascinating about detalimogene is that all of the ingredients that I just described to you are readily available or inexpensive. And we're able to put them together in a proprietary manner. The result is we have a product that we've already gone through our FDA validation batches. We're manufacturing at scale. So this is a product detalimogene that is easy to handle, can be stored in a regular fridge or a regular freezer, but we should have the lowest cost of goods of all the immunotherapies.

Okay. Great. And you've reported a good amount of data from your pivotal cohort in the LEGEND study thus far. Maybe just from a high level, what have been key takeaways from the interim data that we've seen so far that you'd highlight?

Yes. I think we're excited that detalimogene is an active and useful product. The primary endpoint for approval in this category is complete response rate at any time. Ours is 54%, which is in the range of approvable products. The next thing that the FDA looks at is safety and tolerability. So being a nonviral gene product, quite safe, I described fitting in your refrigerator. But from a tolerability standpoint, we seem to have one of the lowest levels of AEs. And in particular, if I draw your attention to treatment interruptions or treatment discontinuation, real measure of are people taking the medicine, ours is 2.4%, very low. So we're trending towards best-in-class handling, best-in-class tolerability.

Also below that, what was interesting is that over 90% of the patients responded within the first 3 months. So they responded very quickly. If they didn't respond, less than 3% progressed. So very little risk of using the product early, and you'll know very quickly if it works. And what we're waiting for is our data to mature from a durability standpoint. We have very early 12-month data, 12-month landmark data, and we have very early durability of the patient -- the percentage of patients that are durable 12 months and beyond. That's what we'll get later this year.

Okay. Great. So speaking of that, you've guided to that 12-month data later this year. And it sounds like BLA submission could come after that. So what are you hoping to see in that update? What profile do you think would support regulatory approval in that update?

Well, you think about what does the FDA look at? The FDA first looks at the risk benefit in any category, right? So what's the risk? For us, first of all, as I said to you, we're trending towards best-in-class tolerability, trending towards best-in-class safety and handling. And the risk is this is a new approach, right, a new platform. The FDA likes to have -- they've approved 4 different agents, types of agents. This will be totally different. So that's on the risk part, which I would say relatively low. And the primary endpoint is CR any time. That's heavily weighted. Ours is 54%, in line with the other products.

Now what the FDA is looking for is some durability data, right? So -- because if you have a 54% CR any time and you have 3 months of durability, it's not very useful. But if you have something like the majority of the patients approach a year, that gets competitive. So we'll have that data, 12-month landmark data in the second half of the year. Not as much of the 12-month durability data. That package will go in together, and that will form our planned BLA initiation.

Okay. And I think you said you have a planned FDA interaction later this year, so ahead of the BLA. So is there any insight you can give us into maybe key points you'll be looking to discuss with the agency in that meeting? And then again, I guess, just how much of this 12-month data do you think you'll have or do you think would be helpful to have for the meeting?

Yes. So the meeting itself, you covered 2 topics. You cover manufacturing and clinical. So we -- the FDA has given us CDRP, which is a special program for manufacturing. So we're always in dialogue with them, but we will go and ask them a couple of questions about our manufacturing is sufficient. And then on the clinical stuff, we will -- it's pretty simple. Do we -- does the FDA believe we have sufficient enough data to initiate the filing? And I think at that time, we feel pretty confident that we'll have a sufficient amount of data to be able to do that.

Okay. And I think you've talked about alignment with FDA on the SAP to potentially exclude some patients for the efficacy analysis. So can you remind us of the context for that discussion and give us a sense of the range of potential outcomes on exclusions? Are there certain patients you're fairly confident could be excluded? Where does that discussion stand?

Yes. So with any pivotal program, you have a discussion with the FDA on the statistical analysis plan, quite normal. If you see within some of the other products, they have a publication number with X, right? And in their label, Y. And this is the process that we're under. We've made a proposal to the FDA. The FDA has come back to us. So we're in that back and forth period. I think our upcoming pre-BLA meeting will help clarify that further, but we would expect that our final label will have less than the 125 patients that we've enrolled. And again, 125 patients makes it one of the largest programs. So to lose some patients is not going to have much of an impact.

Okay. That's helpful. And then maybe just one more on the regulatory front, and we've discussed this before, but with the evolving treatment landscape here and organizational changes at FDA, there's more and more talk about single-arm trials and maybe the sentiment is that FDA is more amenable to those these days versus maybe a few months ago. But I guess just any thoughts on kind of trial design and how the evolving nature of staffing at the agency could impact receptivity?

Yes. I actually our interaction with the FDA has been nothing short of phenomenal, right? So what do I look at? It's not that long ago when Inlexzo was approved, right? So the path is still there. The second thing is if you look at other companies that are coming into the space, they've been very clear with them that their studies are not second-line studies, they're third line. So ours is BCG then our product. Any new product is BCG, a new product and the third product.

So they've been pretty clear with that. And I guess then the third thing is I look at our level of engagement and the FDA does not hand out very easily things like RMAT designation, CDRP. We've had the same project managers. We've had the exact same clinical reviewer. I feel pretty confident that we deliver the package that we're planning on delivering. We're in very good shape with the FDA.

Okay. Great. And maybe just transitioning to the potential commercial launch for detalimogene. You and the team have done a lot of interesting work to understand the market and the unmet need here. So if we think about detalimogene's unique profile, how is it positioned relative to other treatments? And how does that factor into your launch strategy?

Well, I think you have to step back at the market, first of all, right? So the market is, let's call it, 25% academic, 75% community. Detalimogene was designed for community urologists. And in fact, when you survey, do market research for community urologists, what do they say they want? They say, well, we want something that's efficacious that our patients will take that's tolerable. And that's easy to slide into our practice. That is the detalimogene profile. With a 54% CR rate any time, it shows great efficacy with a very low treatment interruption or discontinuation rate, patients will stay on the medicine.

And in fact, detalimogene is probably even easier than BCG to integrate into the practice, given that it will sit in the freezer for what we expect to be years and in a regular fridge for many months. It's not going to require much resource from a staffing perspective because with detalimogene on its own, there are no prewashes. You don't need to have urologists administer it. It needs to be a medical professional, reach into the freezer, mix it, instill, send the patient home. So that, to me, is pretty compelling proposition for those community urologists have very few options.

Okay. Great. So maybe just diving a little bit deeper into that. Is there further segmentation you'd highlight between kind of academic and community practices? Are there different levels of receptivity to detalimogene versus maybe a more onerous treatment in the work that you've done?

Yes. So our market research shows that there's a unique position for detalimogene. So if you -- it's easy to characterize all urologists the same. Then you can say, okay, let's split them by academic and community. And that still is still fairly simple as well. Within the community, we can go down even further to find segments that are particularly attractive to detalimogene. So there are practices. So if you look at that from a numbers perspective, that's 25% -- 20% to 25% academic, 75% to 80% community. And within that, we've identified over 40% of the practices have unique attributes that detalimogene would actually solve a big problem with us. And these are resource-constrained practice, economically focused practices where the profile of detalimogene differentially could be very special there.

Okay. Okay. That's helpful. And then just thinking about efficacy as these urologists are considering their profile here. We've broadly talked about CR rate at any time and durability. How are those data points weighed in different practice settings so that urologists thinks differently about those endpoints?

Yes. Market research is pretty clear. A CR anytime is in the land of community urologists. Do this product work or not, right? And with no disrespect to any community urologists, if I ask them about the 12-month number for them, they will -- they likely will not be focused on. Because remember, they're treating a wide range of patients, right? Does the product work or not, CR anytime.

For the academics, where they're much more focused in on patients that are very experienced, right? They, in general, would almost want to prefer to remove the bladder. The patient doesn't want to remove the bladder. They're very focused in on durability and the highest efficacy possible because they also have the benefit of resources. So where we see detalimogene being used with the community is very early in the treatment because as I indicated to you before, works fast, it doesn't work. There's very little damage, right? You can continue on to something else. And quite frankly, our early signs pretty good efficacy and pretty good durability.

Where we talk to the academics, they're used to be more focused on the fact that it's nonviral. So they're juggling different types of chemo, immunotherapy, having a nonviral approach for patients. So we probably would see more third or fourth line usage there.

Okay. And then one more just on kind of the breakdown of the population here. So it sounds like about 40% of those community practices would potentially be rapid or excited adopters of detalimogene. Can you give us an idea of how many patients are seen in that subset of practices? Is it kind of one-for-one in terms of practice?

Yes, that is the patient number, right? So, if you think about it, 75% of the practice are community; within that, detalimogene could be attractive through all 75% where 40% of the patients are, there are differential attributes of detalimogene that unlock that practice that other products just cannot do. So that is a real differentiating point where something special like detalimogene can make a big difference.

Okay. And you touched on it. It sounds like dependent on practice setting and the patient, obviously, where detalimogene could slot in terms of treatment sequencing might be different. But I guess, is there an overall profile you're thinking about will this also depend on where the patient is treated?

Well, I think like in multiple myeloma, these doctors now have the opportunity to have a real dialogue with their patients. And it will be very practice-specific and patient-specific. So the combination will be something along the lines of -- I'm sorry, Judah, your BCG is not working. I've got 2 or 3 here are the pros and cons of these agents, right? You have to come in every 6 weeks and it doesn't work, it's another 6 weeks, intense therapy.

I'm going to insert a device into your bladder. Here every 3 weeks, you have to drink 1.5 liter every day. You're going to feel that, right? Or I can start you with something like detalimogene or we're going to know within 3 months whether it's working. You come in week 1 and 2, week 5 and 6, super -- it's very well tolerated, and I can start you right now, right? So I think that's where the benefit of detalimogene really differentiates itself.

Do you get the sense, I guess, kind of beyond burden on the patient, which it sounds like is a large consideration here. Are there certain urologists considering mechanism and therapeutic mechanism when making these sequencing decisions? And how -- what is that thought process as it's evolving there?

I think that's more in the realm of the academics, right? Because the academics -- because remember, let's step back a little bit. This is a disease, it's cancer. It's very serious cancer. However, it progresses at about 20% over 10 years. So it's a slow cancer. It's also a cancer that's affecting -- the average age is around 70, 75 years old. So these are people that are getting a little older, right? And they have comorbidities, generally, they're smokers, right? So the treatment choices and objectives are different, right?

How can we control this bladder cancer so the patient may pass from something else, right? And so for the academics, I think they like to go immunotherapy, chemoimmunotherapy chemo. And if one of these products is not working, then I think the mechanism makes a big difference. Nonviral gene therapy is something different. It's less important for the community. The community is more driven about what can I get my hands on, what will my practice administrator use, what fits into the flow. And in both cases, detalimogene can be a useful product.

Okay. And you mentioned, you think kind of 2, 3, maybe more lines of sequencing before radical cystectomy. I guess in your payer conversations, what's the reaction on that side of the table in terms of potentially limiting the degree of sequencing? How are you thinking about how many lines payers are kind of willing to accept?

Yes. Market research says probably more than 3 or 4 lines of therapy, given that a radical cystectomy is such a severe outcome. And in our payer research, if you have NCCN guidelines, in general, you're going to be reimbursed. So this is not a large barrier to uptake for detalimogene.

Okay. And I guess speaking of the competitive dynamic here in the sequencing, what are your latest thoughts on pricing? Can you remind us of kind of the relevant benchmarks that are going to be valid for detalimogene? And in those payer conversations, do you have any insight into where pricing could head?

Yes. So the range in pricing for these products is $220,000 to about $700,000 a year. As we've had dialogue with payers, our payer research goes back to what I said before, it's cancer, it's serious. It is -- if it's on the NCCN guidelines, it's generally going to get reimbursed.

Okay. That's helpful.

And what's interesting that it kind of changes the picture a little bit because at the new benchmark pricing $700,000, that's 2,000 patients that you need to hit $1 billion, which when I talk to you about incidence of 20,000 to 40,000 patients per year, there's lots of room for lots of agents.

Right. That makes sense. And as you think about a potential launch, can you give us a sense of the level of investment required to build out commercial infrastructure? What could a sales footprint look like? What are the particular call points that would maybe be first to tackle as well?

Well, what's great about this is it is quite viable for a product -- for a company like ours to launch the product. We'll need about 40 to 60 sales reps as a proxy. When you think about these community practices, these LUGs, say there's 30 doctors, 30 urologists, 3 or 4 focusing on bladder cancer. So we're able to target those individuals with that sales force. So very much well within the abilities of a company like us.

Okay. Great. And then I just wanted to touch on the surfactant bladder rinse cohort that you recently initiated. So what was the impetus behind that? And how might it enhance detalimogene's profile? And I guess, at what point in the clinical or commercial kind of launch of the drug would this factor in?

Yes. So when we designed detalimogene, we designed it for community urologists, unlike other products, no pre-washes, very few instillations and no after treatment activities needed for high-risk NMIBC. We had always thought of bringing forth a surfactant bladder rinse for other indications as well. When you look at the other gene therapies in their preclinical data, they get very little transfection without a bladder rinse.

We actually with detalimogene without a bladder rinse, we do get a pretty significant amount of transfection. You see that relates into pretty good clinical efficacy. In our preclinical models, we see IL-12 expression going up as much as 10x with a pretty mild surfactant called polidocanol. So we selected polidocanol. It's approved drug. It's got a lot of safety information. It's actually used at up to 1% in a lot of shampoos. And what we've done is, to still again, we're always trying to make our drug more efficacious and simpler. What we've done is we've reduced the dwell time from an hour to half an hour.

Now remember, these are generally incontinent gentlemen, right, with bladders that are beaten up, hard to hold it in. It will be easier to hold it in. And very simply, what occurs is you put polidocanol in, let it sit for 5 minutes with the catheter, take it out, you put detalimogene in and you tell the patient to keep it in for half an hour. So the net of that is patient actually saves 25 minutes. So we expect to have better convenience for the patients, better experience for them, and we expect to have better durability, efficacy and durability given what the preclinical data is. We're already up and going with the cohort. We've just gotten through the safety run-in. So we will have data very soon, and this has been an important part of the urologist's armamentarium.

Okay. Great. We look forward to that. So maybe in the last couple of minutes, you may remember from last year, we do kind of a mini survey that we ask all of our companies touching on kind of a few topical areas that are of interest to biotech investors these days. So first, with China's rise in biotech innovation, how are you thinking about your competitive position here? And could this influence your R&D or business development strategy?

Well, where is China gone? China used to be a place to go for manufacturing and manufacturing things very quickly and inexpensively. And now they've just moved up the curve on innovation. I think for us, specifically, as it relates to detalimogene, it has relatively little impact for us because we're so far along the line for commercialization. But as we consider business development and building out the platform, the technology that's available in China becomes very interesting for us. So I really -- at the end of the day, we're here to get new medicines to help patients. The boom in innovation in China is really going to be helpful for patients here in the United States and around the world.

Okay. Would you say enGene is leveraging AI in a particular way or thinking about the potential for AI to disrupt the space that you're in?

I would say in the early part of it, when you think about AI, AI in our industry really started it in the discovery part, right, in identifying compounds. We've already developed a platform. We've already translated the platform. So now the AI is probably more about how do we commercialize. And again, there's a lot of interesting agents to help our commercialization and particularly a small company like ours, AI actually allows us to probably punch a little higher than previously. So I'm kind of excited about some of the work the team has been doing.

Okay. Great. And last, we touched on it, but on the regulatory side, it sounds like FDA has been relatively stable in your interactions. But anything else, whether it's at the agency on pricing, maybe MFN, tariffs, anything that you're thinking about on the regulatory side that kind of keeps you up at night?

I would say from -- first of all, on the FDA, you're always wondering because things can change. But I would say even in the stormiest times, our stuff has been absolutely boring, which is fantastic. Boring is good. Tariffs are, again, something to think about. But again, as a company that's not commercialized, not, it's still around the edges, right? Unfortunately, as we commercialize, it's something we have to think about. And MFN puts -- that's the one part where you think about a product like detalimogene really is an attractive drug for the globe. Easy to handle, right? So MFN is something that where we have to keep one eye open and just see how that evolves over time.

Okay. Great. With that, we're out of time, and thank you again for the time today, Ron.

Judah, great to see you. I Appreciate it. Bye-bye.

All right.

Good morning, and welcome to the enGene Therapeutics call to discuss the non-muscle invasive bladder cancer market. [Operator Instructions] 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, everyone, and thank you for joining our call to discuss new insights to the non-muscle invasive bladder cancer market. Joining me on the call this morning are Ron Cooper, our Chief Executive Officer; Amy Pott, our Chief Global Commercialization Officer, and we're pleased to welcome Dr. Neal Shore, Medical Director for the START Cancer Research.

Before we 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 detalimogene, the efficacy, safety and product profile of detalimogene, timing of clinical data, timing of regulatory submission, prospects for regulatory approval of detalimogene, projections of market opportunity and market share, the anticipated market acceptance of detalimogene, if approved, our current views on end market research on the non-muscle invasive bladder cancer market, implications or takeaways from our market research, estimates, projections or forecasts of payer coverage of therapies, our expectations regarding how health care providers may use detalimogene or sequencing of products.

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 made 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. Thanks, Lauren, and thank you all for joining us this morning. We're really excited to discuss how our views of the high-risk BCG unresponsive NMIBC market have evolved with the in-depth market research we've conducted over the past months where we use multiple product profiles. We're also very pleased that Dr. Neal Shore could join us today to provide his perspective. Welcome, Dr. Shore. Before turning it over to Amy, I will provide a short overview. Our product candidate, detalimogene, is the only novel nonviral gene therapy being developed for NMIBC. It is administered intravascularly to the bladder where it delivers plasmid DNA encoding 3 genes that activate the RIG-I pathway and drive expression of IL-12, synergistically stimulating both the innate and adaptive immune responses.

We are currently studying detalimogene in the ongoing Phase II LEGEND trial, which includes a pivotal cohort with high-risk BCG unresponsive NMIBC with carcinoma in situ or assist patients. We'll also discuss the new detalimogene plus surfactant cohort, where we expect enhanced CR any time, durability and convenience. And the BCG unresponsive papillary only disease cohort where we expect to achieve NCCN guideline inclusion. We believe NMIBC is transforming into a rapidly growing market as more therapies become available, creating additional opportunities for patient sequencing and expanding the treatable patient population.

In May of this year, we shared interim pivotal cohort data on detalimogene without surfactant during a preliminary session at the American Urological Association Annual Meeting. Only 55% of patients experienced a treatment-related adverse event, most of which were mild, of which only 2.4 were associated with dose interruptions or discontinuations, respectively. For the primary endpoint, detalimogene without surfactant had an anytime complete response rate of 54%, which falls solidly within the range of approved products.

Duration of response equal to or greater than 12 months, the key secondary endpoint is still maturing. A landmark CR at 12-month KM estimate of 25% is similar to adstiladrin and approved product. As Amy and Dr. Shore will discuss, we believe that detalimogene's overall efficacy, tolerability and handling profile as the only nonviral gene therapy may provide a unique and desirable profile for integration across a number of community urology practice settings. Importantly, our nonviral approach also utilizes readily available low-cost components that support scalable manufacturing and simplified storage and handling.

Notably, we have completed our PPQ or FDA validation batches and then FDA, CDRP, Chemistry, Manufacturing and Controls Development and Readiness Pilot Program designation supports BLA readiness. Importantly, we also see an opportunity to further enhance the profile of detalimogene through the addition of a surfactant bladder rinse. In preclinical models, both murine and NHP, this approach has demonstrated an eight- to tenfold increase in IL-12 expression. We believe that a surfactant bladder rinse may enhance the efficacy of detalimogene without compromising the tolerability profile. In addition, the use of a surfactant rinse is anticipated to reduce the bladder dwell time of detalimogene from 60 to 30 minutes, further reducing burden on patients who frequently suffer incontinence and bladder spasm.

Looking ahead, we anticipate mature durability data will be available later this year, plan to meet with the FDA and initiate a filing by the end of the year. Importantly, we remain well funded with $285 million. To summarize, we see 4 important themes. A growing NMIBC market supported by increased sequencing. Two, a differentiated nonviral platform designed for community adoption. Three, a promising clinical profile to date. And four, the potential opportunity to further enhance that profile through the addition of surfactant.

I'd now like to turn the call over to Amy Pott, our Chief Global Commercialization Officer, to take you through our market research findings. Amy?

Thanks, Ron, and welcome, everybody. We have conducted extensive market research over these past few months where we've tested a range of efficacy profiles, payer dynamics and practice considerations when considering therapies for high-risk BCG unresponsive NMIBC patients. Our market research supports and informs assumptions we will share with you today. The depth and breadth of this market research is as good as anything I've delivered from my days in big pharma and is a robust mix of qualitative and quantitative research.

To give you a sense of our extensive approach, over the period of 6 months, we've conducted multiple waves of market research, including over 65 urologists and uro-oncologist interviews, 15 payer interviews, 2 100 urologists and uro-oncologist surveys and analyzed over 2,000 patient claims. We've also conducted over 20 clinical literature reviews with the aim to capture emerging and future trends that will impact the NMIBC market. On the next slide, we can see these are some evolving topics that we would like to make sure you have insights on as we think about the high-risk BCG unresponsive NMIBC market.

The first 3 assumptions in any market model for NMIBC are pretty straightforward. Most of the literature and claims data would align on the first 3 inputs, an annual incidence of about 90,000 new cases of bladder cancer each year, 80% of those being NMIBC and drilling down to about 30% of these cases falling into the high-risk category. Where there is some ambiguity is around the last 4 categories, including the size of the potential population who have CIS and papillary only, BCG unresponsive classification, market share and pricing dynamics.

Today, we will share the insights we've gleaned that are helping to inform our views around these dynamic market assumptions. Slide 10 here reviews the 2 separate subcategories of high-risk disease, including CIS and papillary only, although the 2 can occur concomitantly. While papillary is typically resected by a TURBT and then treated with BCG in the high-risk setting. CIS is multifocal in nature and difficult to treat surgically. In the next slide, when we're reviewing patient profiles of high-risk patients, it's important to understand clinical guidance as to how to treat high-risk patients. Treatment algorithms within clinical guidelines for CIS represent a wide range of patients. And it's clear that papillary-only patients are clinically managed and reimbursed like CIS patients.

The NCCN guidelines have set consensus treatment standards for CIS patients with categories within the guideline. 2A category reflects NCCN consensus that the treatment recommendations are based on appropriate evidence for both CIS and papillary only. It is also important to note that all our interview payers indicated that they would cover BCG unresponsive therapies broadly with a 2A plus recommendation. The detalimogene LEGEND study includes a cohort of papillary-only patients. Should we receive FDA approval on our pivotal cohort, we would plan to submit for inclusion of NCCN guidelines.

Bottom line, our market research indicates that the addressable BCG unresponsive population is larger than many believe. In the next slide, NMIBC represents a unique market. There are currently approved therapies and others in clinical trials, but there is no one therapy that suits all patients and practices. In our HCP market insights and other published surveys from patients, there is a clear desire to avoid radical cystectomy. All our urologists interviewed stated that they would aim to sequence patients through 3 or 4 lines of therapy before performing a radical cystectomy. Here, we have captured an illustration of how patients could sequence through 3 or 4 lines of therapy and the compounding effect this will have on the eligible pool of patients.

Currently, community urologists have few viable treatment options, but with the advent of next-generation products like detalimogene, sequencing will drive growth of the prevalent population. This pattern has been observed in numerous therapeutic categories where innovation expanded the overall market rather than simply redistributing share. As new treatment options become available in diseases such as multiple nonmyeloma, multiple sclerosis and depression, more patients ultimately receive treatment and remain on therapy longer. It is well accepted that most patients with high-risk NMIBC are treated in community settings. However, through our market research insights, we've gained much deeper insights into different drivers of choice and practice needs.

Our findings also reveal that there is a slight difference in prevalence and incident rates with an estimated 75% of incident NMIBC patients seeking care in the community versus 80% of prevalent NMIBC patients. Through our new market research insights, we have dug deeper into the choice drivers for small and large private practices and have characterized these practices into 4 different categories, practices that are resource limited, practices that battle with workflow and logistical constraints, practices that prioritize economics and practices of clinical excellence.

This has allowed us to sharpen our view of the percentage number of patients in the community. Here, we can zoom in further and understand how patients are being treated across these various practice settings, further segmented by their key considerations. Over 40% are balancing a range of complex needs, including resources, economics and efficacy. Our research uncovered that within the private community-based practices, there are 4 distinct segments, of which 3 express meaningful preference towards adoption of a product such as detalimogene, where its efficacy profile, ease of use and tolerability is uniquely well suited.

First, we have resource limited practice where adoption of novel therapies is limited by cash concerns. Second, workflow-constrained practices where uptake of viral therapies is limited due to infrastructure or logistical challenges of administration. Third, economic focused practices where net cost recovery in consideration with efficacy drives adoption. And fourth, clinical excellence practices. Dr. Neal Shore, who will be providing insights later, runs a very sophisticated private practice and represents one of the clinical excellence practices. However, he can also provide insights on the needs and behaviors of all of our segments.

Per Slide 14, here is where we illustratively show the feedback from our market research on where we think there would be meaningful market share of detalimogene in approximately half of the market and minimal in the other half. This shows a competitive profile and ability to have share in multiple segments. We tested a range of efficacy profiles from adstiladrin-like efficacy to lower efficacy. In all cases, the feedback from HCPs collected in our market research leads us to believe that detalimogene's unique profile generated meaningful market share in attractive community practice segments.

Here on Slide 16, we can see that with the exception of hospital health systems, 80% of urologists are using buy and bill to acquire NMIBC therapies. While economic-focused practices are keen to integrate novel therapies, the potential to provide a therapy that balances efficacy, tolerability and ease of use to workflow-constrained practices who'd like to utilize buy and bill, but can't administer complex therapies will be important to increasing the menu of options they can provide to patients. Likewise, close to 20% of community practices are resource limited and wary of large cash outlays. So the ability to address these concerns will be an important factor. We believe it's key to note that there are a range of factors taken into consideration when pricing a product.

When thinking about efficacy, there are multiple measures, including complete response as well as durability. Safety is, of course, important. Inlexzo, for instance, launched at a higher price point than Anktiva despite having less durability. And as noted on the slide, we've repeatedly seen similar pricing dynamics in the highly competitive I&I space. Another key dynamic assumption is the payer reimbursement and price benchmarks within the NMIBC market today. The overall benchmark has moved up from an annual wholesale acquisition cost, WACC, of $220,000 per year to $690,000 per year.

Based on our market research interview with payers, we believe that interviewed payers will cover therapies at parity, assuming NCCN guideline category of 2A and importantly, private practice urologists clearly indicated that the net cost recovery is critical for building practice infrastructure and capacity. Generating a positive net recovery and efficient practice sector on economics, particularly in a buy and bill marketplace is both important and common across multiple therapy areas, not just urology.

On Slide 9, we have an illustrative example of net sales for an approved NMIBC product and projected revenue at priority pricing at a new watermark. If an NMIBC therapy is priced at parity with recent benchmarks, only about 10% of the eligible patient pool needs to be on therapy to achieve roughly $1 billion in net sales. In conclusion, with new and emerging market trends in NMIBC, BCG unresponsive, it's important to understand some of the dynamic market drivers. To recap, the real-world treatment algorithms for CIS patients could represent a wider range of patients. Papillary-only patients are clinically managed and reimbursed like CIS patients.

With more therapies becoming available, but still high unmet need, HCPs and patients indicate that they would be willing to sequence and try up to 3 to 4 lines of therapy to avoid radical cystectomy. This will create a compounding effect on the eligible patient pool. Understanding the drivers of choice across private practices is key as it demonstrates differential market share by practice type. Our research suggests that relatively few emerging therapies are well positioned across resource-limited, workflow-constrained and economic-focused practices. We believe detalimogene can address these needs and has the potential to become a leading agent in community urology.

The benchmark price for NMIBC therapies has moved up and allows private practices to build towards net cost recovery and efficient practice economics as well as the important ability to offer patients bladder-sparing treatment options. We hope you found these new market insights thought-provoking. I would like to hand over to Dr. Neal Shore so that he can provide you with his thoughts on our research findings and the realities of managing NMIBC patients in the community. Dr. Shore.

Well, thank you very much, Amy, and thank you, Ron. It's a great pleasure to be here this morning to be part of this discussion. I am the Medical Director of Carolina Urologic Research Center and the Head of the GU Oncology Consortium for START Cancer Research. I'm also an investigator for detalimogene. I've had the privilege of being involved in over 100 different bladder cancer research trials from all the aspects of NMIBC through MIBC and metastatic urothelial carcinoma. And I've taken care of these patients throughout the entirety of my career. I'm really pleased to share my perspective today, both as a community, uro-oncologist, and investigator, educator and an author.

So when you think about what happens in a typical community urologic practice, these patients with high-risk NMIBC, they usually present in their mid-70s when they become BCG unresponsive. And not that long ago, once a patient did recur after BCG, particularly typically with high-risk NMIBC, the shortages have really kind of relegated us to just treating this population now. The conversation really shifted very quickly to radical cystectomy, which is pretty commonplace outside the U.S. and even was historically the U.S. perspective. And so that really is the sort of the standard of care in many parts of the world. But a lot's changed because while we recognize that cystectomy is an important option, there's no doubt about it, particularly in high volume experienced centers, yet there still is an obviously major morbidity and a real mortality in the short term. Patients don't really want to undergo a life-changing surgery, that should be pretty obvious to all on this call, that has these risks of morbidity and mortality, especially if they're not having bladder voiding dysfunction in the setting of non-muscle invasive disease.

At the same time, physicians don't want to see their patients progress to muscle-invasive bladder cancer, which is a real inflection point in the bladder cancer journey, where they will require more aggressive therapy, perioperative strategies, cystectomy, possible partials, et cetera. The good news is that non-muscle invasive bladder cancer is often relatively slowly progressing to muscle invasive, although there is a real possibility for it in our high-risk patients. And we've had numerous recent pivotal studies that have shown the rate of progression to muscle-invasive disease can be kept, if with appropriate monitoring, into the single-digit percentages, which gives us an opportunity to intervene with additional therapies and potentially preserve the bladder longer.

So what I've seen change dramatically over the last several years is the emergence of new BCG-unresponsive treatment options, which I think has been fantastic for the field, and really kudos to all the investigators who've been part of that, and really appreciate the FDA's forward thinking in their approval strategy. So we're moving to a world where patients were quickly referred for bladder removal to one where, especially in the United States, patients may be sequenced through multiple therapies before considering cystectomy. That is clearly the state of the art right now.

I think it's better for patients. It also now allows community urologists, uro-oncologists, and medical oncologists to play an increasingly important role in managing these patients, where heretofore they were very rapidly shifted off to academic medical centers. And with this increasingly important role, community practices want to do what they can to avoid that referral, both because for multiple reasons, convenience for patients, there's always autonomy issues. There are clinical and economic modeling that can be mutually beneficial. Patients prefer to have this. They like this continuity of care. They have a trusting relationship, presumably with the patient and the provider team, which has been built over many years of surveilling their non-muscle invasive bladder cancer. So at the same time, the treatment landscape is becoming therapeutically more complicated, more crowded, thanks to all the recent approvals.

And most community urologists are not strictly focused on bladder cancer. They have other GU oncology and non-oncologic focuses. They're managing the full spectrum of oncologic and non-oncologic disease while caring for a high volume of patients. As more therapies become available, it becomes increasingly difficult to stay current on the nuances of every product, the different MOAs, the different side effect profiles, the resources required, pending J-codes, et cetera, and reimbursement. So physicians, in my opinion, will naturally gravitate towards therapies that they understand well, including their administrative teams that have simpler administration profiles, less scheduling toxicity, time toxicity for patients, and what's going to be least disruptive to their practice flows or what some people call the throughput.

When it comes to adopting new therapies in community practice, I think we have really three types of toxicities. I've sort of mentioned them. There's the logistical toxicity, the personnel toxicity. How many medical assistants do you have? Do you need to have an RN to administer? Can it be done by an LPN? What is the requirement for a physician oversight? And then of course, time toxicity to the patient. More and more I see this not only in high-risk NMIBC, but throughout all aspects of GU oncology.

Logistical toxicity includes the storage, the handling, the operational requirements needed to deliver a therapeutic safely and efficiently. For the viral therapies, practices need to consider freezer capabilities, thaw time, sometimes ventilator hood requirements, PPE requirements. Many of these really vary on a state-by-state basis and regulation regarding preparation and administration. So that also has to be understood on a state, a local investigation.

Personnel toxicity is equally important. What do I mean by that? Community practices continue to face physician shortages, particularly in uro-oncology. We see shortages in nurses and nursing turnover. Nursing services are highly sought by competitive hospital-based centers and other forms of the healthcare community competing for their services, no longer just working in the hospital and in a physician's office. There's also the limited staff bandwidth for many of the patients or I should say the personnel who would want to work in practice. So the drug device combinations, for example, which have been highly effective, they require procedure room time, urologic physician involvement, and some staff resources to further manage the adverse event profile. Community practices have to carefully evaluate how much additional burden any one of the approved and pending approval therapies such as detalimogene places on already stretched administrative personnel, clinical, and workflow concerns.

And I mentioned time toxicity. The treatment frequency, the schedule of events that patients have to endure, I am asked this on a repetitive basis now, not just in bladder, but also throughout GU oncology. The dwell time, the procedure time, and the overall time spent in the clinic will have an influence on patient decision-making as well as their experience. From a practice standpoint, room utilization in the clinic, the physician's time, the nursing time, allied personnel, LPNs, MAs, and the patient throughput are really critical considerations right now in this field. And we're all learning contemporaneously. Detalimogene features fewer induction doses than traditional BCG and the potential to reduce with their new surfactant protocol dwell time from 60 to 30 minutes. And I think that's going to be really interesting to see, and we're certainly hopeful that it has comparable, if not even improved efficacy.

So beyond these toxicities, physicians must also consider economics and reimbursement. We heard a very nice analysis. There's the sort of spectrum between the economics and efficacy. That's just a real-world consideration, undoubtedly. How is the product acquired? What are the cash outlays? What is the net cost recovery? This is where the health economics to the practice bottom line becomes very germane. These questions matter because even though a therapy can be remarkably clinically attractive, if a practice cannot operationalize it, cannot justify it, absorb the financial risk, it can impact adoption. That doesn't seem always fair, but that's just the cold reality of it.

And of course, physicians and patients must consider the burden placed on the patient, tolerability, visit frequency I alluded to already, post-treatment precautions such as the GU hygiene for bleaching, et cetera, in the home and other additional caregiver and patient instructions. And the lifestyle and impact all become important parts of the shared decision-making process. Shared decision-making is now the standard of which we have to have this very important conversation with patients and their caregivers. In a world with increasing options, patient-provider discussions around treatment goals and options, they continue to burgeon, and patients are highly involved in the decision-making process. They're much savvier than they ever were, clearly with not only AI and social media, but also it's just the access to information and education.

I could present multiple options to a patient, but ultimately, it's the patient who must decide which treatment best fits their goals, lifestyle, family, and tolerance for risk and burden. How risk-averse or risk-seeking are they? Yet there is still work to be done to always ensure that patients in community settings have access to the same range of options as we see in our tertiary centers and our academic centers. That is ultimately the goal, the North Star for what we do.

So when I review the data on detalimogene to date, what stands out is the overall profile, so taken completely in context. We saw at AUA 2026 in May, my colleague and good friend, Ashish Kamat, he presented the efficacy data. The most recent appears to be tracking toward the level of efficacy we have seen with other approved therapies. For example, Adstiladrin, while potentially also offering a very safe and tolerable profile with limited schedule of events. So these attributes to me and my colleagues are going to be very appealing. I think in a disease that generally progresses slowly if monitored carefully, many will be inclined to use therapies that are going to be better tolerated, easier to incorporate into a busy personnel-constrained practice.

So if we can determine with ease whether a patient is responding early or not, and it is well-tolerated, that is going to give me a lot of confidence that I can continue in that therapy in that patient's bladder cancer journey. Or if not, we can always switch to something else. I think that is a really big, interesting, dynamic, and developing field, this area of sequencing, prior to saying, "Okay, I am throwing in the towel, and I am proceeding to radical cystectomy." So my goal as a practitioner, as a prescriber, is to help patients and their families avoid or delay cystectomy whenever it's safe and appropriate. Does require expertise by all the practices and a team to do it.

Patients want to preserve their bladder. They want to maintain their quality of life. They want treatment close to home. The therapies that will be most successful are those that can deliver meaningful efficacy and recognizing that they need to fit into the realities and practicalities of both patients' lives, and as was already said, 80%-85% of this is going on in community practice. I will just conclude and say that what I have seen so far, detalimogene has very strong potential to be a compelling option for these patients with high-risk NMIBC.

With that, I would like to hand it back to you, Ron.

Great. Thanks, Dr. Shore, for sharing your perspectives. In summary, we hope that today's event has provided you with greater insight into the NMIBC market. I would like to close by highlighting our belief that the BCG unresponsive market is larger than many believe. That there currently is minimal sequencing in community practices. The advent of viable new therapies will drive sequencing and drive up the prevalent population. There are different types of community practices where the detalimogene profile is uniquely suited, even with varying efficacy profiles. There is a new price point for these therapies, which is near $700,000 a year. At this price point, a therapy requires only around 2,000 patients in order to generate over $1 billion in net revenue.

In conclusion, detalimogene's efficacy to date, tolerability, and simple handling may provide a unique offering to a large swath of community urologists who are currently limited in viable options that they can integrate into their practices. We look forward to our plans to meet with the FDA later this half and initiating our BLA submission this year with a potential approval and platform designation in 2027.

With that, I'd now like to open up the call for questions.

[Operator Instructions] Our first question comes from Maurice Raycroft at Jefferies.

Maybe just starting off with one for Dr. Shore. Dr. Shore, given the similar efficacy profiles we've seen with Adstiladrin and detalimogene, can you discuss what percentage of your patients currently get Adstiladrin versus other approved treatment options as a reference point?

Sure. Happy to. Yes. We're fortunate to have now accessibility to Adstiladrin, Anktiva, Inlexzo, I'm using the commercial names here, as well as Keytruda for these BCG unresponsive patients, CIS, CIS papillary. We also have several ongoing clinical trials, including detalimogene. I have about 15 partners. We don't mandate one particular protocol. We look at a patient, and we say, "We have access to these varying therapies," assuming that their insurance/accessibility is not an issue. We describe to them the workflow, we describe to them the time commitment. We describe to them the different adverse event profiles which each does have.

And so, it's somewhat evolving because of the recent approvals, and getting the J-codes in position. I would say we're using all of them. We try not to be -- We don't reflex to one versus another. I hope I'm not sounding like I'm avoiding your question, is that we like to do clinical trials. We did it in all of these drugs that have been approved. I'm certainly optimistic that detalimogene will get approved. Then, we meet and we discuss with not just the physicians, the team that's doing the administration, and we also then, too, look at the economics as well as how our patients are experiencing it. So I would say right now, without giving you exact percentages, because I honestly don't have them at the tip of my tongue, I would say we're probably almost equivalent in the approved therapies with the exception of using pembrolizumab.

Okay. I guess difficult to provide a reference point percentage of patients at this point.

Well, I would say percentage wise, 98% will get a BCG unresponsive therapy or clinical trial. And looking now at it, if someone finds one intolerable or there's some other reason not to continue with it, we are 100% sequencing. That's a really interesting and evolving field. There's not a lot of prospective clinical trials on that, and I do think we'll start to see that going forward.

Yes, makes sense.

I think Maurice, Dr. Shore is indicating pretty much equal between the approved agents.

Got it. Yes, makes sense. And then maybe just one other question for the company and maybe for Dr. Shore as well. Just wondering how you characterize the optimal pricing sweet spot for NMIBC drugs, recognizing that while a higher price can drive stronger economics, it can also create some cash flow constraints for certain practices. So how should we think about that, especially relative to detalimogene?

Yes, Maurice, it's Amy here. I can take that. So I think, with pricing's always one of the last things that you do. However, I think what we've heard from payers and HCPs is that it's about really understanding the reimbursement part and the prioritization part. I think once you have those pieces kind of completed, then what we've heard is, around the net cost recovery, is it's the same whether you have a price point at the lower price point or at the higher price point. So once you've had to get over the hurdles of prior auth, reimbursement, that helps to understand the kind of marketplace. So whilst we haven't got to our pricing yet, I think what we've been able to show is it is an evolving marketplace.

Our next question comes from Sean McCutcheon at Raymond James.

For Dr. Shore, does the market research that was presented today parallel your view on sequencing and use of three to four novel therapies ahead of radical cystectomy? And can you speak to your experience and preferences, with sequencing and with the currently available therapies? Then separately, have you seen pushback from payers to this end?

Yes, as a researcher and as a clinician, I find this to be a remarkably exciting field. We sometimes say it's a bit of an embarrassment of riches. We went from virtually nothing, radical cystectomy, overutilization of BCG, and BCG with some chemotherapy, to now having really efficacious novel MOA therapies. And so in our practice, I'll just speak to my three decades of being in this, in my most last few years with these approvals, when one BCG unresponsive therapy isn't working, and based upon a repeat biopsy, and the patient has persistent high-grade disease, not necessarily muscle invasive, but Ta G3 or CIS or T1, unless they have a dysfunctional bladder, they're like, "Okay, what else do you have for me, Doc?" I say, "We've got two options. We've got standard of care therapies, and we have clinical trials." They're like, "Okay, I want to hear more about that."

Because it's a very morbid procedure to have your bladder removed and have to wear an ostomy and/or have a continent diversion. We have had some trials recently, and I participated in it, which if patients can get through that surgery without complication, they actually can do pretty well. That said, it's still obviously one of the biggest life-changing, body-changing surgeries that we do. And in the community, they're being performed less and less.

So yes, patients will want to have the discussion for further sequencing. That has been the experience. I think that'll continue to be the experience. It's early days. Many of the smaller groups, and there's still a few thousand of them out there in the United States, are learning through our conferences and through educational events to learn how to do -- to bring into accessibility within their clinics. That's where I really think that the surveys that you heard from Amy 100% resonates with my experience.

We have tremendous heterogeneity in the clinical workforce. It's a very different world to be part of tertiary academic centers, typically in metropolitan areas. They see 15% of the patient population with bladder cancer, and frankly, for all oncology. Then you get into that other 85%, which I thought the breakdown of those four groups was frankly brilliant, and we talk about it all the time, and the issues of the real world implementation, workforce issues, the economics, and the efficacy. I 100% agreed with everything that Amy laid out to you. I think that to their credit, they did a very nice job in their interviews and their surveys.

Maybe just to follow up, have you seen any payer pushback on sequencing of some of the recently approved therapies?

Yes. Thank you. I knew I missed that one on you. Sorry. I personally have not. To say, "Okay, well, then we have to proceed to cystectomy," I have not had a pre-op discussion with any physician from any of the different insurances that we used, including managed Medicare.

I would just add there that of all the payer interviews that we did, there wasn't any kind of pushback. Again, as I highlighted in the presentation, if you're included in the NCCN guidelines at 2A and above, you would get reimbursement.

Understood. Thank you.

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

Maybe one question for Dr. Shore, and it would be great to get Ron's opinion on it after. As we look at the NCCN guideline inclusions, how different were those data packages submitted to the NCCN guidelines committees across those agents? I guess trying to get a sense of beyond efficacy, what seemed to matter most to those committees? If a 2A recommendation was enough to get you the broad payer parity, what are some of the other things outside of the obvious efficacy and safety that those committees weighed across those packages? Have you identified any maybe imbalances or inefficiencies that detalimogene's package could leverage to get into those guidelines more effectively?

Hey, Andres. I think I'll just take that one. Quite frankly, when you look at the products that have been approved and the products to come, we're all following the FDA guidance for how we conduct our trials. Now, there are some subtle differences, inclusion criteria and exclusion criteria, and in the protocols. And I think what we've seen from an NCCN perspective, since they're relatively standard, that is what they've used to determine whether inclusion within the guidelines. So we would expect, since our approach is similar to those that have been accepted for NCCN guidelines, that we would achieve those guideline inclusion as well.

Maybe one quick one for Dr. Shore. Obviously, the sentiment is to avoid bladder cystectomy. For those community urologists that tend to perhaps be slightly more aggressive on when they recommend radical cystectomy to a patient, can you just maybe on a broad level explain to us what are some of their genetics? What is their phenotype of thinking, which makes them slightly more aggressive? Obviously, preservation is the key here, but we've come across some urologists that just tend to be a little bit more aggressive in that sense. Would love to get your high-level thoughts there.

Yes, I really appreciate that question. Look, one of my partners is a fellowship-trained surgical oncologist, and he's trained to do radical cystectomy, robotic-assisted, both with traditional ileal conduit and continent diversion. There are many of these surgical uro-oncologists who are out there. I got into urology, frankly, because of my desire and love for doing cystectomies. When I was a medical student at Duke University, and I did a clerkship at MD Anderson Cancer Center, I found myself in that room all the time.

That said, even in high-volume centers, there are some challenges. To your question, I have great respect for my colleagues who have great results. There's always the possibility and likely scenario that the surgical oncologist can list to their patients, "Oh, I saw too many patients who didn't get the right treatment, the non-surgical treatment at the right time. Too much BCG, too much mitomycin followed by another chemotherapy, or so on and so on, or delays in follow-up, and then they showed up." There's a certain, to your point, the DNA, the perspective of patients who might have not had optimal experience.

I don't want to lose the emphasis that these patients need to be followed and monitored very rigorously by physicians who understand the different therapies and the different options, and they need to have the team and the discussion with the patients. And so I think that could be part of that, and not to overly simplify it, but there's the old expression, when you have a hammer more and more things tend to look like a nail. And I don't mean to say that in any kind of disparaging way, but if you're really good at doing something and you know that you can get good results, I can understand that philosophy. And I think it's not unreasonable, and that's why the shared decision-making conversation with an experienced cystectomist versus somebody who's really well-schooled as well in understanding all of these new novel therapies is going to be the state of the art right now.

Our next question comes from Lili Nsongo at Leerink.

Maybe a question for Dr. Shore. So as it was stated in the slide, BCG unresponsiveness, that has been quite difficult to estimate. I was wondering, how do you define unresponsiveness in your own practice? What portion of your patients does that represent, and how much BCG supply constraints have constrained your practice this year?

Yes. I had the privilege of being part of the FDA workshop, gosh, several years ago, where we came up with this more codified definition of unresponsiveness, which is largely the 5 + 2 or the 6 + 6 in repeat induction after CIS. We are very good about recognizing that. That said, I wouldn't say that all of my colleagues have followed that. There has been -- Even within my own practice, and regionally and nationally, we still see many patients who may not get the five of six induction, who may not get the two of three maintenance, and then they just stop for whatever reason. They didn't want to have a cystoscopy, maybe there was a BCG shortage, they were moving, et cetera. It's been more than 12 months since they've had their BCG, so it's almost as if they get rediagnosed, then they're really starting from scratch.

The BCG shortage has been vexing. We have been impacted by it. It's always somewhat unpredictable. Certain different parts of the country, whether it's Southeast versus Midwest, Northeast, West, not everybody is hit at the same time. There is supposedly going to be a new plant coming online maybe by the end of the year or early next year, who knows, that'll have greater production capacity. We have been hearing that for some time. We all look forward to that. Additionally, we're hopefully getting other BCGs potentially approved, whether it's the Tokyo strain or the recombinant strains from the Serum Institute. I think that will certainly help. Split dosing. Some folks have done that. We've not been very successful in doing that from a throughput standpoint.

And maybe a follow-up on data interpretation, or I guess in comparing treatment options when just thinking of efficacy. My question is, how much weight do you put on CR rate compared to DOR, duration of response? Also, how much weight do you give progression to muscle invasive versus recurrence?

So the progression rate to muscle invasion is very important. All therapies, we certainly look to make sure that they can delay that progression, delay the need for cystectomy, and do so in a way that doesn't result in metastatic disease. And again, that goes back to my comments about the importance of strict monitoring with these patients. I think that the different CR rates are a wonderful debate that we do in the community. We have a Bladder Cancer Academy that this'll be our 15th year we do that. We have panels and we discuss in a very realistic, real world experience, how do different providers describe this to patients to exactly your question.

Are you just going to have the scientific clinical CR at 6 months, 12 months duration of response? The answer to that is no. That is not what happens, is that we do have to talk about how is the therapy administered. Will it be administered intravesically, intravenously, orally? Are there devices related? How much time do you need to be in the clinic? It goes without saying the patients expect that we will take care of their benefits verification and pre-authorization. And then of course, the big question patients ask in addition to the schedule of events for them and the mode of administration is tell me about the safety profile. What can I expect? As a general rule, these are patients in their mid-70s now. Sometimes I think these are the young patients because I see so many high-performance patients in their mid-80s. So they are very much more attuned to the safety profile.

And Lili, I would just add, from our market research, it seems that the community urologists are focused on the CR any time, so does the product work or not? Whereas the academics are more focused in the durability part of that. Thanks for your questions.

Our next question comes from Yanan Zhu at Wells Fargo.

For Dr. Shore, I was wondering, when you weigh convenience and of the myriad of factors and toxicities that you highlighted, which is super helpful, including scheduling, personnel, patient time, logistical, of all of that, if we can aggregate that as the convenience factor, if you weigh that against efficacy, I was just curious on two fronts. One, is there still a minimum efficacy profile that needs to be met? If so, could you articulate what that might be? Ron just mentioned anytime CR as something that a community doctor will focus on. If you can lay out a wholesome efficacy profile for a community practitioner, that would be super helpful? Then I have a follow-up regarding sequencing.

Yes, I think that, look, once a therapy achieves FDA approval and NCCN recognition or AUA or EAU, then it really becomes that shared decision-making moment. I think that certainly, having a CR in the mid 20% range at 12 months, it qualifies for discussion. Certainly, CRs at 6 months. And also recognizing that you are monitoring these patients. If you decide to move to something else, you can, and that's okay too.

For patients, I'll just kind of repeat. There is a segment of patients who are more data-driven. I think it's the minority. Who are savvy and sophisticated in terms of just looking at trying to do cross-trial comparisons, even though we always caveat that that shouldn't be done until you do the direct comparative prospective study. But that's the minority of the patient population. I'm not saying that they're any less smart or more smart. They are more driven by the safety, tolerability, and convenience, and making sure, of course, that there is economic accessibility. Ideally, if you have all of those things, great efficacy, tolerability, schedule of events, mode of administration, delivery, then that will sort of enhance the product profile.

Great. That's super helpful. You did talk about sequencing. So I was wondering, in terms of sequencing what therapy to use earlier rather than later, how does our earlier discussion about convenience and efficacy come into that perspective? Or it doesn't really contribute to the ranking, so to speak, or the ranking order in which the patient receive these therapies. For the company, it looks like in a slide deck, you have kind of, a hypothetical attrition at each sequence, second line, third line, and at each step, there is a 50% loss. Is that like a very conservative? I was wondering what went into that. Is that the patient no longer needing therapy and being in long-term response on the prior therapy, or is that because the patient progressed? Just trying to get a sense of, is this number very conservative or it's the best estimate that you currently have?

Why don't you take that, Amy?

Yes. I think on the question of sequencing, and I think it's the 50% in that slide that you're referring to. I think that is our best estimate. Obviously, with everyone still understanding how these patients will be sequenced in the future, but we've sort of looked at it from a range, and that would be the median range that we would highlight here.

Got it. And when sequencing these therapies, does the convenience, the efficacy factor come in and determine which drug is used first?

Yes, I think as Dr. Shore indicated, these are holistic discussions with his patients, and I think that's what our market research says to individuals. As you kind of go through the mix of, here's the efficacy profile, here's the tolerability profile, here's the burden of how often you have to be in, here is the post-treatment requirements. That's a holistic decision. That's where the balance comes in. Thanks for the questions, Yanan.

Our next question comes from Judah Frommer at Morgan Stanley.

Maybe for both Dr. Shore and the company, maybe just thinking about the 12-month data that we'll get in the back half of the year, anything we should be looking for there that could impact decision-making in clinic post a potential approval? And then how could the surfactant bladder rinse cohort and time to data there impact a potential ramp in the commercial setting? Do you have a sense that docs may be waiting for that surfactant bladder rinse data and potentially an updated protocol, or do you think that conversations are already productive just with the data that's in hand thus far?

Yes. Let me take both of those, Judah. I think that when we gave our presentation earlier this year on the AUA data, what we were saying is the data looks like with a 54% CR rate at any time, that is in the range of approved products. From a durability perspective, Kaplan-Meier said that the 12-month landmark, which is not a secondary endpoint, and it is not a promotable endpoint, we are trending towards the Adstiladrin profile. Then the durability is still to come. You see the range of approved products, that is within 40%-50%. And I think that when the FDA looks at our total durability package, that we feel that we will be in a fileable zone. Nothing really different than what we shared before.

I think as it relates to the surfactant, because we have selected polidocanol, which is an already approved agent, has a lot of safety data. If you look at the other gene therapies, they have used a surfactant to increase expression. Without a surfactant in preclinical models, they get a very little transfection or no transfection. With the surfactant, they get a boost in transfection. We have seen a pretty significant boost in transfection in our preclinical models, and so we are already up and going with a surfactant cohort. There is a lot of enthusiasm within the medical community, within the research community.

The first part of the protocol is a safety run-in, the first time we take it to patients. So we are looking forward to updating the market later on. But we would anticipate that we will get a detalimogene-only approval sometime in 2027, and then we will supplement that later on with surfactant data.

Our final question comes from David Dai at UBS.

I have two questions for Dr. Shore. The first question, just around, Dr. Shore, are you using all the approved therapies right now? If you can just give some numbers around, let's say, there's 100 patients that are BCG-unresponsive, what percentage of these patients are receiving each of the approved therapies?

Secondly, on sequencing, one thing you mentioned is just you're looking to get detalimogene into different sequencing in bladder or BCG-unresponsive patients. How do you envision the detalimogene would fit into the different sequencing in BCG-unresponsive NMIBC patients? Are these going to be second line, third line, or fourth line?

Hi, David. Maybe the first one Dr. Shore answered previously. Just to reiterate, I think his comment was that each patient they have a dialogue with, and in the new therapies, he's been using those products equally. Maybe you want to make a comment about sequencing, Dr. Shore.

Yes, I think that I like the sequencing question. That's evolving. Look, the first of these that came on board was, many years ago now, was the Pembro. As somebody who was embracing IO therapy, I actually used it a fair amount, and that never took hold in the urologic community, I think primarily at the time because of concerns and a requirement for education on immune-related adverse events. That's changing.

And I was involved with the development of Adstiladrin and Anktiva, as well as Inlexzo. Inlexzo just most recently in this year got its J-code, that our adoption for that has started to increase significantly. The Anktiva we've started to use as well, especially since we've had access to the recombinant BCG.

And then, of course, Adstiladrin really because of its early adoption or its early approval and our involvement in the trials was taking sort of the bigger share. I would say that is all sort of to some degree redistributing, and it is an evolutionary process. And we still in some patients will do intravesical chemotherapy as well.

All right. I think we wrap it up there, operator.

Yes.

All right. First of all, many thanks, Dr. Shore. Thank you, Amy. Thank you all for joining us. We look forward to providing additional updates later in the second half. Thanks for hanging in a little bit late with us as well. Have a good day.

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.

Great. Thanks, everyone. My name is Etzer Darout, senior biotech analyst at Barclays. It's my pleasure to have enGene with us this morning, CEO, Ronald Cooper. Ron, maybe if you can just give us an introduction of enGene for those that are less familiar with the story, and then we'd take it from there.

Well, enGene is a unique company with unique technology at actually a really unique time, right? So our technology is called the DDX platform. It's a proprietary sugar platform that we developed ourselves over many years. The lead asset from our platform is a product called detalimogene, which we're developing for non-muscle invasive bladder cancer. And we're right in the middle of an open-label pivotal study. And so it's an exciting time.

Detalimogene itself is a nonviral gene therapy. So that confers a lot of benefits, very unique. And this year is a pretty exciting year for us in that first off -- first up in Q2 of this year and spring of this year, we will be providing -- we plan a data update at an upcoming scientific conference. In the second half of this year, we plan to share the long-term data, 12-month data for our pivotal study, which is fully enrolled.

So we'll have the final results of our pivotal study. We have a planned filing of the BLA, and we expect an approval in 2027, you wrap that up, a company that has cash is over $300 million. We have cash in the second part of 2028. That's why I said it's a unique company, unique technology at a very unique time.

Awesome. Great. Based on our conversation with KOLs, non-muscle invasive bladder cancer feels potentially larger, I think, than I think the market assumes certainly higher unmet need. Maybe if you can comment on sort of the disconnect, if you will, between sort of how the market views this opportunity and sort of how key opinion leaders are talking about it.

Yes, this is a market that's undergoing a lot of transformation. So the first misnomer is that people are very focused in on breast and lung as big cancers. But first of all, bladder cancer is #6. So it's a top 10 cancer, right? So it's pretty large. And then NMIBC within that is 700 and prevalence is around 740,000 in the U.S. So that's quite large as well. What people are not quite understanding or the transformation that's occurring is when you think about NMIBC, traditionally, if you were diagnosed with that, the only real treatments that you had were BCG and removal of the bladder.

And urologist said, well, you have cancer. If you fail BCG, we're going to take your bladder out. Increasingly, though, it's understood that NMIBC is a slow progressing disease. So progress is about 20% over 10 years and maybe even lower than that. So now all of a sudden, the treatment paradigm is changing. But with this slow progression, there were no treatments, right? And so now there are a number of new treatments that have been approved and that are in the pipeline to be approved. And so what's going to fundamentally change is products are going to be sequenced out for each other because these products they have -- they kind of wear out a year later, right?

There are recurrence rates anywhere from 60% to 80%, right? So quite significant. So they will be sequenced. The patients don't progress, but they recur. The analogy that I would use for this is a little bit like the multiple myeloma market, right? When Revlimid was launched, it was a $1 billion market. You add a dozen-plus new products, it's a $20-plus billion market as products are being sequenced. I think the same thing is going to happen here. The bladder cancer market is about a $2 billion market. It's projected to be a $20 billion plus because of the reasons I just talked about.

Right. And sort of with that, can you just highlight, obviously, this is sort of a space where competition is growing. If you can highlight detalimogene's differentiation relative to what we sort of see from other molecules and maybe also describe the mechanism of action and how that relates to the differentiation here.

Well, first of all, as I said, we're the only nonviral gene therapy. So by itself, it is super differentiated and super unique. And that confers a lot of interesting benefits. I think the way to think about that, first of all, is let's flip it around from the customer perspective. The majority of the patients are with community urologists. When you ask community urologists, what do they want? What do they need?

Obviously, they need products that have efficacy. They need products that are highly tolerable because these patients are generally -- and this is underappreciated, are 75- to 80-year-old smoking men with comorbidities, it's tough to get them on treatments. They don't really want to bother with this sort of slow cancer. So tolerability is important. But the third thing that's important are some of the nonclinical benefits, how easy it slides into their practice does it consume resources.

So when you think of detalimogene, it's probably the only product that delivers all 3, right? So it -- our preliminary data shows that we have a CR rate that's very competitive, good efficacy. We have probably best-in-class tolerability, very low discontinuations, very low treatment interruptions. But in particular, community urologists, because we have a nonviral approach, our product can be stored in a regular freezer for many years, in the regular fridge for many months. There's no special handling.

So if you compare this to some of the other products, right, that require special handling that require prewashes, that require decontamination of rooms, that require hoods, right, that require procedure rooms, right? We don't have any of those things, right? So detalimogene is a really unique product because it provides the efficacy that doctors want, probably best-in-class tolerability. Most of the patients don't discontinue, most of the patients don't have treatment interruptions and probably best-in-class handling and ease of sliding into those practices.

And with that, when you think about sort of your go-to-market strategy and how you plan to sort of reach those community docs? Is there any education that needs to go on given that it's a slow progressing disease? How are you thinking about that?

Well, I think, first of all, from a go-to-market strategy, we think about geographies first, right? And in the U.S., we believe that we'll need 40 to 60 sales representatives, which is very manageable for a company like ours. So we're ready to go. In Europe, our go-to-market strategy, we're still evaluating. I and a lot of other members of our team have a lot of experience in Europe, and that will be a financial decision, whether we go on our own or whether a partner and the rest of the world will partner.

So then within the U.S. itself, how do we think about this? Well, within these community practices are often organized in what I call LUGPA's, right, which are a collection of practices. But within a LUGPA, there are usually a handful of doctors that are really focused in on bladder cancer. So we will be targeting them, right? We also have to really think differently about our targeting from how the practices work. And I'll tell you why, right?

Because in the U.S., the #1 specialty that does buy and bill is oncology, right, number one. The second one is urology, right? So this is a big source of revenue for their practices. But when you segment the practices, some practices are very sophisticated in what they do and they do a lot of buy and bill. Some practices would really like to do that. But right now, the technologies that have been -- the first-generation products are just clunky for community urologists.

And detalimogene is a next-gen product. So it's really going to slide in [ lower ]. And then there's a third group that really haven't explored buy-and-bill and do a lot of referring. So we will be, first of all, targeting the first 2 groups, and we think we can really activate the community urologists because we have a next-gen product that really fits our needs as I talked about earlier.

Great. And then maybe -- sorry, with the registration study, first announced data in 2024 sort of for LEGEND and sort of the amended protocol for the study. Can you talk about sort of maybe a little bit more around that amendment, what it entailed and sort of walk us through now the sort of the next data update and what we can expect from that?

Yes. So the journey for us in our pivotal cohorts, the pivotal study is the LEGEND program. Cohort 1 is the pivotal cohort. When it was designed, it was designed by a CMO who is an oncologist. And we just realized we're going to be a urology company, better have some urologists here, right? So the team figured that out, which is terrific, right? But urologists said like, okay, like why are you making this harder run yourselves? You're not even applying standard of care for these patients, right?

So we had some good data, initial data in 2024, but then we made 3 pretty significant protocol changes that brought us in line with standard of care. First one being is before patients even got into the study, the T1 patients, so the T1 patients are higher risk, standard of care is to resect their T1, that lesion and then do a second time. And we weren't doing the second one. Now they all have to get that second resection.

The second thing is that as patients got to 3 months, if you had a little TA growth and papillary growth, we said you're out of the study. And the doctor said it's just a little growth. There's nothing happening with cyst. We just cut it out. That's standard of care. Now we allow them to do that. And the third thing that we do is we ask for biopsies before patients come on before doctors would look and say, "Oh, it looks like it's progressing."

But sometimes with immunotherapies, the bladder gets red. So it's a much more objective or subjective approach. You take that and you wrap it around the fact that our -- again, with a different approach of doing the study, we brought in a very strong clinical operations team that if you take those protocol changes, mixed with better execution, better follow-up there you go.

And the results that we shared late last year are really compelling and much better, frankly. And then what we're expecting is a data update at a major congress in the spring of this year, that's planned. And there, what we hope to do is really focus in on the primary endpoint, which is complete response at any time. So it's 3 and 6 months for us. So that will be locked in because we have about 125 patients and most of those patients would have reached their 6-month time frame. So it's a pretty exciting time.

Good. And I guess the obligatory question these days is sort of alignment with the FDA on the protocol change. And I guess as well as sort of how you're kind of thinking about the pivotal readout and whether or not, again, the FDA sort of you and the FDA are aligned with that. And again, also, how does that compare to sort of peers, if you will, in terms of their pivotals?

Well, the FDA has been terrific with us. Now remember, when you think of the FDA, very rarely do they have guidance in there. They recognize the need in NMIBC, right? And so the guidance that they originally put on 2018 and then reiterated draft guidance in 2024 that if you do 100 patients or so open label, you'll get a complete approval. And what's nice is that a number of products have even recently have got that. So it's pretty rare in all of the things that they do, and I would call that rock solid.

We've had a good dialogue with the FDA. And the FDA has provided us a number of important designations. So we have Fast Track, we have RMAT, we have CGRP. And I don't think they give those to companies unless they are serious about working with us to bring this product across the line. So we've had very constructive dialogue with them. We shared our preliminary data with them, which has resulted in some of these special designations. So I think we feel pretty good about being on track for working through the filing in the second half of this year.

Great. And how does the protocol compared to other programs, this is bond program, SunRISe, how does the protocol compared to...

Well, I think I'm always -- I always caution people to make comparisons, right? So first of all, we do not have access to their protocols, right? So we don't know for a fact. But from their publicly disclosed information, what you see is many of the changes that we've done seem to be similarly done with them. But I always caution people to compare against these particular -- I know it's human nature to compare. But first of all, the patient population, inclusion criteria, patient populations are very heterogeneous, right?

So NMIBC patients are very different. I believe the protocols are different. And then in these studies of 100 patients or less, right, you can see a lot of swings. So I believe that we're roughly aligned with others. But again, I would just caution individuals to make comparisons between the study, even though it's human nature because there are different patient populations often and often different protocols.

Great. Yes. And then maybe another change if you could comment on, is there a meaningful difference or maybe the reason driving the change from complete response at 12 months to sort of complete response at any time? Like what's -- is there a meaningful difference there? And then maybe what was the motivating factor for that change?

Well, that's just sort of standard discussion that we started in a particular area. We started to talk to the FDA. And the FDA said, look, this is the primary endpoint for all the other products that we've approved. So we would expect that to align. So primary endpoint is CR any time and the key secondary endpoint is duration of response.

Right. And how -- with the potential for sequencing of these different therapies, I guess, how do you see the NMIBC space evolving over time? And where do you think your program fits into that sort of paradigm?

Well, again, I believe this is a real transformation that's going to occur. First of all, you have to think about the customer groups, right? You think about where are the patients. Over 80% of the patients are in the community, right? About 17% from our market research are in the academic centers. In the academic centers, these are places where they remove bladders and they're really focused on efficacy, and they have the resources to use some of these new technologies, right?

So some of the newer products that are approved and the products that have come along actually sit very well there. But these new next-gen products where we lead with detalimogene are actually ideal for the community. And right now, most of the new products just don't work very well for the community flow, right? So what we see is in the community that patients will be diagnosed because that's where the patients are.

Well, they'll start with BCG if they could get them. Then a nonviral approach like detalimogene because it's just so easy in their office, right? We'll have a product sitting in the fridge. Literally, anyone in the practice can take it out of the fridge, mix with water, regular catheter, instill it into the patient 5 or 10 minutes they're out, right? That's a lot simpler than a lot of the other technologies. So we believe there's going to be a transformation with these next-gen products and some of these other newer products will continue to be used in the smaller specialty area.

Got it. And for detalimogene, do you think about opportunities for the program beyond BCG unresponsive NMIBC with CIS? What where else can this program go?

Well, I think what's really exciting about our -- first of all, our platform is -- our platform can be applied in many areas. Our technology can be applied in many areas. Detalimogene specifically, we've already started a couple of additional cohorts in patients that are naive to BCG, those that are exposed to BCG and those that have papillary only and don't have cyst. So those cohorts are ongoing.

And we're also looking at some of the other areas as well because one of the nice things about our product is being a nonviral gene therapy is the only one. It can be -- being a nonviral product and not being an LNP, the cost of goods in manufacturing this is actually relatively low. So that allows you to go to a wider range of diseases. And because the handling is a lot easier as well. It also allows you to go to a wider range. The potential for detalimogene outside of its first indication is pretty significant.

Right. And you just talked about sort of manufacturing. You're participating in the CDRP pilot program. Maybe you can describe what that is? And then also sort of, again, as you kind of talked about before, the differentiation of detalimogene from just historical NMIBC program that has sometimes struggled with manufacturing.

Yes, really great question. Well, first of all, we're very honored the FDA granted us CDRP. It's a pilot program, 1 of 9 companies. It's given on the basis of great innovation, but also clinical data and clinical need. And to your point, when you think about in the old days, complete response letters were for clinical reasons, now they're mostly for manufacturing, and it's been more so in this category. Effectively, what this means though, rather than taking module 3, the CMC module and kind of throwing it over the fence when we file, we actually start engaging in an early dialogue with the FDA.

We open the kimono, we say, here's what we're planning. They give us feedback more, there's a little less of that, et cetera, et cetera. And that will significantly reduce the risk of CRLs. Now we always thought because, a, we've been manufacturing at scale. We're pretty much finished our PPQ batches, our validation batches. So we'll be writing module 3 very soon.

And because our product takes readily available ingredients and there is no -- it's not a virus, it's not an LNP, we lined up with a product that has relatively low cost of goods. And because it's not a virus, the handling is a lot easier as well. So it makes it very competitive. So I think CDRP is a real help for us and certainly reduces any risk that we might have on the manufacturing front.

Great. And what type of feedback have you gotten from key opinion leaders in bladder cancer around the detalimogene as well as sort of how it sort of compares to competitors?

Yes. Well, first off, I actually never consider them to be competitors, right? These are complementary medicines. And the reason I say that is if there was a product that had a 12-month complete response rate of 80% to 90%, that would be a competitor. That would be the #1 product that's being used. But most of these products have an anytime CR rate of around 2/3, somewhere in that range. And the products have a 12-month rate of 20% to 40%, which means patients are going to recur.

So all these products are going to be used. They're just going to be used in different places and in different sequence. We just believe that when you think about the needs of the community urologists, the first-gen products, they're not really using very much because they just don't fit their needs. They're just too clunky to use, right? These next-gen products where detalimogene is leading, I think, really fits to where the patients are and are going to -- it's going to transform -- be able to start the transformation of this marketplace.

Yes. Great. And then obviously, for your upcoming data disclosures, if you can just talk through what good looks like in terms of benchmarks or hurdle rates when you think about sort of what is a good data set, what is not a good data set as you think about sort of these upcoming disclosures?

Well, these are experiments, right? So you never know exactly where you're going to land up. But I think in our spring conference, right, if we -- that's where we'll be focusing in on the CR any because most of the 125 patients would have hit the 6-month time frame, right? And if you look at the range of products in that, they range from sort of 50 to 60, 70 range of CR any time. So let's see where we land up. We had a CR rate of any time, 63 on the preliminary.

So if we're within that range, I think that sounds good to me, right? And then in the second part of the year, we expect to have the 125 patients, the majority of them would have reached the 12-month time frame. And again, it's an experiment. And the range there is 20 to 40, right? We think we're going to be competitive on both ends. So I think that we feel pretty confident this being an immunotherapy in our durability as well.

Great. I was beyond CR, right, obviously, sometimes you kind of have trade-offs and efficacy, safety and convenience as well as just think about other parts of sort of this data set that beyond CRs that you're going to be looking at and trying to educate investors about.

Yes. That's a very good point. I almost skipped over probably one of the most important things, right, is the tolerability, right? Again, think of these patients, 75- to 80-year-old smoking comorbid men, right? They don't want to have a hassle, right? And if you look at our clinical trials thus far, we have a discontinuation rate in the very low single digits. We have treatment interruption rates very low, where other products are in the 40s and above. So the tolerability for us is going to be very competitive. And that's going to be important.

And I think what Wall Street is missing is that particularly for where the patients are in the community, these newer products are just too difficult for them to use to get into their practice flow, cost them too much money and too much resource. Our product is going to differentiate so nicely. It's going to slide right into the practices. In fact, it's going to be easier than what they've been using in BCG. So that's going to be a big benefit.

Yes. And it looks like we're up on our time. But, Ron, thank you so much for your time today. Thank you for our listeners, and we'll be back soon with our next session.

Great. Appreciate the opportunity. Thank you.

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.

Welcome to the session of the Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the SMiD biotech analysts. We're excited to have enGene joining us. And let me just go through a quick disclosure before welcoming Ron.

For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So again, thank you for being here. Maybe we just start out for those less familiar with the enGene story. Can you provide a brief introduction to the company and your lead asset?

Well, first of all, thanks very much for the opportunity to be here. We really appreciate it. So enGene is a company that has nonviral gene therapy. And that is unique, unique. So when you first of all, when you think about gene therapies, you think about some of the shortcomings of gene therapies. But in fact, by delivering gene therapy through the mucosa using our Special DDX platform, we've been actually able to solve some of those issues.

So first of all, we're able to give a big genetic cargo. We're not limited by cargo. Our products are redoseable, and we can use them over and over again as needed. And because it's nonviral, our manufacturing is a lot simpler, right? So our cost of goods should be competitive, which allows us to get to many more diseases. So I think we sort of cracked the code in some of the challenges of gene therapy.

Now from our platform, which we call the DDX platform, our lead asset is a product called detalimogene. We're developing that for non-muscle invasive bladder cancer with cysts that are BCG resistant. That product is currently in a pivotal study. And we are delighted to announce this very recently that we actually hit our target enrollment for detalimogene. So it's a pretty exciting time for our company.

Excellent. So maybe you mentioned the indication for detalimogene. Maybe we start with unmet need in bladder cancer and how detalimogene might address that unmet need.

Well, first of all, bladder cancer is a pretty common cancer. It's a 6-month common cancer. It's about in the U.S., around 730,000 patients and about 83,000 patients each year. It's a growing population that's associated with the agent, right? And the current treatments, the base treatment is BCG, product that's been in a chronic backorder. And then patients have a few other approved agents, but they often land up having their bladder removed, radical cystectomy. So it's a big population, unmet need, pretty high.

Okay. Great. Here's sort of a high-level question with some subparts, so bear with me. There are a number of competing programs in late-stage development for BCG-unresponsive NMIBC. So if each of these competing programs, and we know one, we'll get to market, where does detalimogene fit? And maybe within the answer, can you help us think about the safety and efficacy profile generated to date, how it stacks up and then the streamlined administration process for detalimogene and how that could impact here?

Well, I guess, first of all, let's -- let's talk about the needs of the urologists. First of all, where are these patients? These patients are predominantly in the community. 70% to 80% of urologists are practicing. So their needs are different. What we've done is we've designed detalimogene for the urologists, right? So based on our September data of last year, we demonstrated really good efficacy, 71% CR rate in time, great tolerability. And you pointed to the last point, ease of administration equals beneficial practice economics in these busy practices, right?

So based on that profile, we really believe detalimogene is the product that community urologists will reach to first for all of those reasons. So now how does that compare to some of the other agents? Well, first of all, if you look at these studies that are being conducted, these studies are not very big studies. They're 100-patient studies, heterogeneous protocols, heterogeneous populations, right? The current products, they have a CR rate between about 20% to 40% of approval. Frankly, I don't know how different that really is, right, in such a small population.

When you actually see these drugs being used in real life, you actually see better efficacy over time. So I would say efficacy seems to be similar for these products. We seem to all be in the same range. So then what about tolerability? We demonstrated in our September 24 data that most of our treatment-related AEs are associated with catheterization grade 1 or 2, very well tolerated. Some of the other agents are also similarly well tolerated, but some of the other agents do have some more serious side effects that can occur. They're rare, but they can occur. So there's a risk benefit for some of the other products.

So I would say we have a very competitive tolerability check. So the third part of the triangle is the ease of administration, which really equals practice economics, right? So let's think about these busy community urology practices. Many of them are owned by private equity. Many of these practices are focused in on how they turn patients -- patients through. If you compare detalimogene to the other products, there's no [ prewashes ]. There's no special handling requirements. There is no co-medications required. There is no after usage bleaching -- effectively, the patient goes in, gets the administration at home.

And the number of administration is relatively low as well. So I really believe I'm excited about where we are with NMIBC because I think all the agents that are there now and the new agents all will have a place, right? And hopefully, that will mean that less patients have their bladders removed. But quite frankly, when you look at sort of the efficacy profile was demonstrated in September of last year, tolerability profile and ease of use and practice economics, it really lends itself to enGene being the product that urologists will reach to first.

Okay. And I think one of the competitors have kind of made the point that if your practice is set up to handle BCG, you'd be set up to handle the competing product. I guess, how -- what's your reaction to hearing that? How many community docs would kind of make the differentiation between detalimogene and handling BCG or a competing product?

These are very different products, right? So BCG is a bacteria. It's an older product that people know and the risk that goes with that. Some of the newer products, which are very potent replicating viruses strike, I don't think it's the same. It's the opposite. Now we'll obviously have to wait to see what the labeling says. But for a potent replicating virus, in general, you need BSL-2 handling.

So you need a hood, you need a nurse that's willing to deal with the virus. You -- after you administer that, you need the patient to stay and collect the urine, bleach that urine and you'll instruct that patient when they go home to bleach the toilet after they void as well. If you look at the recently approved product that's chemo, they're asking for similar types of things even for a chemo agent. So I can imagine it's hard for me to say what the FDA is going to say, but a very potent replicating virus is going to require probably some different handling procedures.

Okay. That's helpful. Moving on to your LEGEND study. You did recently implement some protocol changes there. Can you walk us through those changes, why you made them and what they could mean for future readouts?

So from our data of September last year, as I said, we were pretty pleased about both efficacy and the tolerability. At the same time, we did it with arm behind our back, right? We were not following AUA guidelines and standard -- and standard of care for these patients, right? So we implemented 3 important protocol amendments. And we believe that, that will help efficacy. We left some efficacy on the table.

The first one being is the most serious patients are T1 patients, right? And before, we've allowed patients with T1 disease to have 1 resection and they'd go automatically into the study. Now standard of care says you really should do 2 TURBTs, right, make sure it's not there. And then the big difference for us is if there is still T1, the patient will not be enrolled. And if they have had their T1 removed, it's been proven that, that second TURBT is therapeutic in nature. So what should be the net? We had 14% of our patients that were T1 before.

Our competitor, the other companies that are low single digits will probably be low single digits. We'll probably be in low single digits and probably patients with a better profile. So that's one thing that should make a meaningful difference for us. The second is after 3 months, we -- if there was a little growth, the Ta, a papillary or some sort, we said to the doctors, you have to take the patient out. And the doctor said, well, everything else looks great. We just cut those things out. And in fact, so now we're allowing resection of Ta and allowing those patients to be reinduced.

And that for other companies has made a pretty significant difference in efficacy as well. And the third thing is that previously, when the doctor suspected that there was progression, they looked in the bladder and says, well, that looks red, looks like it's progressing. We would allow them to have them read the study. Standard of care says you require a biopsy, right? So we believe those 3 improvements, limiting the number of T1 patients for making sure we have the right T1 patients and allowing resection of Tas and reinduction and ensuring that there's a biopsy to remove the patients from the study, get us to standard of care and should theoretically at least help us from an efficacy perspective.

Okay. Great. And you will be reporting additional LEGEND data later in the year. What can we expect in terms of the number of patients and follow-up? What are you hoping to see in the context of your own prior data and also kind of as you outlined in the context of competitor data. And the question we get all the time from investors, which CR rate is the right one to think about?

I think I love that last question [indiscernible]. Yes. So I would say so, first of all, based on what I just talked about the protocol changes, I think the #1 thing people are saying to us is, okay, will they make a difference? And that's where we're really focusing our energies on. Now given that we made those protocol changes at the end of last year, we'd like to have a big enough cohort of patients 3 to 6 months where people think, okay, yes, this looks like a difference, right? And so given that enrollment has sort of ramped up sort of at the end of the year, early next year, what we anticipate is sharing of 3 and 6 months, that will be the real focus of what we're trying to.

We're waiting for that point where we have a good sized number of patients where people say, I get it, right? That's where we're focused. Now where should investors be focusing on? But to be honest, I think it's where the doctors focus, right? So if I call the community urologists, right, and ask them about the approved agents, what their 12-month CR rate would be, with no disrespect to them, I'm pretty sure they don't know what that number is in no disrespect, because it's not a focal point. What do they focus on? Does the product work or not, right? And that's CR any time, right? So from my perspective, I look from a customer perspective, they're looking at, does this product work or not, right? CR any time is probably the best proxy for that.

Okay. That makes sense. And a question that I think applies to you guys is not necessarily specific to you, but with some changes at FDA and some surprised CRLs in the space, single-arm trials in oncology have been called out from time to time. And I guess there are some investors that are uneasy. So how are you viewing registrational path for detalimogene currently versus maybe in the prior administration? And any color you can share around just registrational path and confidence?

We have a high level of confidence. You might have seen recently that we received RMAT designation based on our September data. That to me suggests that the FDA sees the unmet medical need that I talked about previously. So they're engaged. I also look at the proxies for our engagement and they've only been very supportive in engaging with us. And then I look at the draft guidance.

Draft guidance came out in 2018. They reiterated the draft guidance in the summer of '24. So -- and the FDA doesn't issue guidance lightly, right? They only do that after they really think it through and that there's a huge unmet medical need. So based on that and based on recent approvals, I think we feel pretty good about where we are.

Okay. Great. And I think you said you're on track for BLA filing mid next year. You've talked about some key leadership additions as you approach potential launch. Can you help us a bit with go-to-market strategy, commercial readiness, manufacturing, things that we should be thinking about as you kind of prepare to launch the product?

Yes. So we are getting ready. We are -- we've already made changes to get ready. I think, first of all, we're in the process already of [ ready ] many of the modules. So we will be ready to just submit as soon as we get the data. In terms of market preparation, you might have seen some recent announcement where we've added 3 Board members that are involved -- have been involved in commercial launches. We added -- we were able to attract a Chief Global Commercialization Officer who's launched dozens of products successfully around the world.

We started to really dig in into the market research and getting understanding of the different physicians because what's really interesting is this a bit of a paradox here, right? So this is a disease that sits predominantly with community urologists. Community urologists are busy seeing patients, right? They're also not really tracking the new medicines, right? And so when people do surveys and they talk to key opinion leaders, their needs are different. First of all, they don't have as many patients.

They're also seeing patients that are 3, 4, 5 lines of therapy, where these community doctors have seen de novo patients, right? So what we've been starting to do is trying to quantify and understand their needs. And so some of the early work that we've done, the profile of detalimogene based on our September data, efficacy, tolerability and that's the ease of use and positive impact on practice economics really makes it attractive. So we look forward to sharing some of that data over time.

Okay. Great. We'll look forward to that. And the LEGEND trial also has some other cohorts that are enrolling patients with other types of NMIBC. Can you tell us about how you think about those cohorts, how they fit into the development plan for the drug and maybe any data we should be looking toward in the relatively near future?

Yes. So we have 3 other cohorts -- in addition to the pivotal cohort, which I said, we've reached our enrollment target. We have a cohort that has BCG naive patients. We have another cohort where they are obesity exposed and the fourth cohort are patients -- the others have cysts -- fourth cohort, no cyst than just papillary. And I think our thinking there is we're really trying to meet the needs of urologists, trying to provide you as much insight in different patient populations, so they understand the totality of the value of detalimogene.

There is some precedent for some of these populations to receive some NCCN guidelines as well, right, which is also useful for the prescribing community. And we provided guidance to say we'll provide an update on those later this year or early next year. But some of that, quite frankly, the priority is in Cohort 1 and enrolling that. So we'll provide more insight on that as time goes on.

Okay. Great. And is there any reason to think that commercial dynamics could differ materially in some of these subsequent populations versus the lead indication in terms of standard -- competing with standard of care or competing with other clinical players in the space?

Yes. I think there is some differences, right? So particularly, like we'll get an indication, and we'll obviously be promoting within the indication for the BCG-resisted with [ Cis ] patients. However, BCG naive patients, there's a lot of logic to the profile of the product would have. And in a country where there is a problem of access to BCG, it becomes a viable alternative theoretically, right? So providing information on that could be interest of different dynamic, right? Obviously, the price point for BCG is quite different. So the unmet needs are different in those spaces. The competitive sets are a little bit different, but we'll really focus on promoting the BCG-resistant patients, right?

Okay. Makes sense. And then just on the DDX platform more generally, where might there be opportunity for enGene outside of bladder cancer? What can you share with us in terms of thinking beyond bladder cancer? Or is that just where you're focused on it right now?

We are focused, right? But below the line, we're doing a lot of work, right? So our team invented this platform. We continue to do work on the platform. And I think what we think about is using the platform, number one, detalimogene, we believe, is a really interesting product, but we always want to life cycle manage that, right? So how can we make it even more convenient? How can we make it even more potent. So there's some thoughts that we have on that. Secondarily is, could we take it to some other cancers, other forms of cancers. And certainly, there's a range of GO cancers where a profile of that product makes a lot of sense.

And then third, we cracked the code for delivering nonviral gene therapy through mucosa, think about it in your body where there's mucosa where we could have good dwell time. And there's some logic for a product like ours or a product from our DDX platform. So detalimogene is the beginning of the story. We continue some really good work that I'm pretty excited about. And then over time, hopefully, as that matures, we'll be able to share more details.

Okay. Great. And then can you just remind us of cash runway and what that runway will fund in terms of clinical catalysts or maybe as we head toward commercialization?

Yes. So the guidance that we've given is we provide a data update in Q4 of this year. We expect to file in the second half of next year, and we potentially will have an approval in '27, right? So that's what's ahead of us. So we're kind of in an exciting period. The nice thing is that we're well capitalized. We have a little over $250 million of cash. And based on our current plans, that gets us into 2027. So we feel pretty good about our cash position. We feel pretty good about where we are from a development perspective, detalimogene.

Okay. Makes a lot of sense. And then maybe just last company-specific question before I get into a survey we're asking all of our management teams. Anything we didn't discuss that you'd highlight around the enGene story?

Well, I think there's one point that we did not talk about, right? So when we think about these products and getting them launched, right, manufacturing has been an issue for these products in general, particularly the ones just viral products in general. And I think it's a place where I think we can reassure folks. In that we've been manufacturing at scale for quite some time. The other nice thing about detalimogene is, really 4 ingredients, right, new ingredients that are readily available.

And with those 4 readily available ingredients, in fact, we're already manufacturing at scale, we will have a pretty competitive cost of goods, right, which allows us probably to do more and to go to other areas. Currently, we are in the middle of our PPP campaigns, right? And they are looking very good. So I think we feel really confident in our ability. And there's always work to be done. So it's some caveats. You never know exactly. But I think we feel pretty good about wrapping up our CMC module even before the clinical data comes, right? So that when the clinical data comes in putting together our filing package should be pretty straightforward. So we're making a lot of progress in that area as well.

Okay. That's helpful color. As I mentioned, we do have a sort of a mini survey we're asking all of the biotech teams at the conference trying to get kind of an overall view of 3 thematic topics. So the first one is on China. So with China's rise in biotech innovation, how are you thinking about your competitive position here? And will this influence your R&D or business development strategy?

Well, I think, first of all, the proliferation of new agents acknowledged from China is a good thing because more good drugs is good for patients overall. I think we sit in a unique position. Our DDX platform is proprietary and it's taken a long time actually to build that. So I don't feel very -- not that concerned about that. And then, of course, from a China perspective, as we go forward from this development perspective, it's interesting for us as well, too. So I think it's a real opportunity for us.

Okay. Great. And then AI is the next theme. How is enGene leveraging AI or thinking about AI's future disruption potential, either on the positive or negative side of drug development?

Well, I, in general, think that AI is really going to be a boom for our industry, right? So if you look at the various different stages, I think the discovery folks have probably been using a form of AI for quite some time actually, right? And it's just gotten better and better. When we get into the development stage of things, not as far along as discovery, but starting to really get into things, particularly biomarkers.

I think we're going to be able to do our clinical studies even better by using AI. From a commercial perspective, I'd say they're probably at the same stage as the development folks starting to dabble into things around the edges that are improving our commercialization. And then I think the last part of the G&A functions, particularly in working with our vendors, this is going to be an opportunity to reduce costs actually. And so I think as we go -- and we already see that, right? We're not a commercial, but I can see some of the things that traditionally that we would pay a lot of money for, AI will replace. So that will actually help us with our commercialization. So overall, I think AI is going to have a pretty big impact on the totality of our industry, and I'm looking forward to seeing in sort of these latter stages and how it begins to help us.

Okay. Great. And the last topic that's been most relevant to most of our SMid-cap biotech companies on the regulatory side of things, and we did touch on this specific to enGene, but changes at FDA, MFN pricing, tariffs, is there anything on the regulatory side of the equation that's generating significant internal conversations at enGene?

I guess the most important one for us is regulatory, right? Because we're at sort of the sharp end [indiscernible] now as we contemplate filing and we already talked about the fact that we have RMAT, the fact that there's already guidance. But to me the most important -- what do I look at from a regulatory perspective? I look at, number one, how responsive is the FDA? And number two, do we have consistency with individuals. Those are the soft parameters. We have the same project manager and that project manager has been really engaged.

And number two, the FDA has been just terrific. They've been right on time or early on things have been very unresponsive to us. So I think from a regulatory perspective, I think we feel pretty good, and we're actually grateful for the support from the FDA. On the other [indiscernible] being a pre-commercial company, there may be things down the line to think about, but they're not really impact issues for us right now.

Okay. Really helpful. I think if there are no questions in the room, we will leave it there, and thank you again for the participation.

Really appreciate it. Pleasure to be here. Thank you.