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 non-viral 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. 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." Those challenges being packet size, redosability, and the manufacturing challenge. enGene was discovered to build non-viral gene therapies, and then, through the discovery process, translated a product called detalimogene, which is the first non-viral 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. We're heading 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. Sitting with $266 million in cash, we're all capitalized to achieve all of those things. Okay, great. Like you said, you're developing detalimogene, and the indication is BCG unresponsive, non-muscle invasive bladder cancer with CIS. 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 is removal of your bladder. So, t he radical cystectomy, and then when I learned more about radical cystectomy, four- to six -hour surgery, multi-organ, 5%-15% mortality, and horrific morbidity as well, individuals landing with an ostomy, loss of sexual function. So, treatment's not very good. When you think about the epi, there are about 90,000 in the U.S., in the instant 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- 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 number six 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. 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 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. Part of the challenge is when you look at the market overall, let's call it 20%-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, 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 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. Then, they have gemcitabine, which they can use, but there's some questions about efficacy, and it's not really financially viable. Then of the new agents, gemcitabine on the pretzel may or may not be viable. 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. With these dynamics in mind, and clearly, 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 does 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 three or four lines of therapies at least, right? That's a big change. 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 was a $1 billion market. Yeah. 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. 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%-50%. What does that mean? At the end of a year, half the patients need another medicine. Medicines like detalimogene can make a really big difference there. Okay, great. 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 factors into detalimogene? So, detalimogene is quite simple, but quite elegant how it's put together. Because, actually, it starts off with a simple generic plasmid. We have two 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 inline 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 matches. We're manufacturing at scale. So, this is a product, detalimogene, that is easy to handle. It 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. 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? Yeah, I think we're excited to show 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 non-viral gene product, quite safe, as described, sitting in your refrigerator. But from a tolerability standpoint, we seem to have one of the lowest levels of AE s. In particular, if I draw your attention to treatment interruptions or treatment discontinuation, real measure of our people taking the medicine. Right. Ours is 2.4%. Yeah. 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 three 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. What we're waiting for is our data to mature from a durability standpoint. We're very early 12-month data, 12-month landmark data, and we have very early durability, the percentage of patients that are durable 12 months and beyond. That's what we'll get later this year. Okay, great. Speaking of that, you've guided to that 12-month data later this year, and it sounds like BLA submission could come after that. 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? Yeah. The FDA first looks at the risk benefits in any category, right? What's the risk? For us, first of all, as I said to you, 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. Yeah. The FDA likes to have, t hey've approved four different agents, types of agents. This would be totally different. That's on the risk part, which I would say relatively low. The primary endpoint is CR any time. Yeah. 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? Right. Because if you have a 54% CR any time and you have three 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. I think you said you have a planned FDA interaction later this year, so ahead of the BLA. Is there any insight you can give us into maybe key points you will be looking to discuss with the agency in that meeting? Then, again, I guess just how much of this 12-month data do you think you will have, or do you think would be helpful to have for the meeting? Yeah. The meeting itself, you covered two topics. You covered manufacturing and clinical. Yeah. The FDA has given us CDRP. This is a special program for manufacturing. We are always in dialogue with them, but we will go and ask them a couple of questions about our manufacturing. Is this sufficient? Then, on the clinical stuff, it is pretty simple. Does the FDA believe we have sufficient enough data to initiate the filing? Right. I think at that time, we feel pretty confident that we will have a sufficient amount of data to be able to do that. Okay. I think you have talked about alignment with FDA on the SAP to potentially exclude some patients for the efficacy analysis. 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 are fairly confident could be excluded? Where does that discussion stand? Yeah. With any pivotal program, you have a discussion with the FDA on the statistical announcement. It is quite normal. If you see within some of the other products, they have a publication number with X, right, and in their label, Y. This is the process that we are under. We have made a proposal to the FDA. The FDA has come back to us. We are in that back-and-forth. Okay. 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. Again, the 125 patients makes it one of the largest programs, so to lose some patients is not going to have. Okay. Much of an impact. Okay. That's helpful. 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. I guess, just any thoughts on trial design and how the evolving nature of staffing at the agency could impact receptivity? Yeah. Actually, our interaction with the FDA has been nothing short of phenomenal. Yeah. 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. Ours is BCG, then our product. Any new product is a BCG, a new product, and the third product. They've been pretty clear with that. 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 designations. Right. CDRP. We've had the same project managers. We've had the. Yeah. Exact same clinical reviewer. I feel pretty confident that. Yeah. If we deliver the package that we're planning on delivering, we're in very good shape with the FDA. Okay. Great. 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. 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? The market is, let's call it 25% academic, 75% community. Detalimogene was designed for community urologists. 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 discontinuation rate, patients will stay on the medicine. In fact, detalimogene is probably even easier than BCG to integrate into the practice, given that it'll 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 pre-washes. You don't need to have urologists administer it. It just needs to be a medical professional, reach it in the freezer, mix it, instill, send the patient home. So that, to me, is a pretty compelling proposition for those community urologists who have very few options. Okay, great. So, maybe just diving a little bit deeper into that, is there further segmentation you'd highlight between 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. Our market research shows that there's a unique position for detalimogene. So, if you, you know, i t's easy to characterize all urologists the same. Right. 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 attracted to detalimogene. There are practices, if you look at it from a numbers perspective, that's 20%-25% academic, 75%-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. These are resource-constrained practice, economically focused practices. Right. Where the profile of detalimogene differentially could be very special there. Okay. That's helpful. Thinking about efficacy as these urologists are considering their profile here, w e've broadly talked about CR rate at any time and durability, h ow are those data points weighed in different practice settings so that urologist thinks differently about those endpoints? Yeah, market research is pretty clear. A CR any time is in the land of community urologists. Does this product work or not? Right. And with no disrespect to any community urologist, if I ask them about the 12-month number for them, they likely will not be focused on it. Because remember, they're treating a wide range of patients, right? Does the product work or not? CR any time. For the academics, they're much more focused in on patients that are very experienced, right? 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, b ecause as I indicated to you before, works fast. If it doesn't work, there's very little damage, right? You can continue on to something else, and quite frankly, our early signs show pretty good efficacy and pretty good durability. Where we talk to the academics, their use would be more focused on the fact that it's non-viral. So, they're juggling different types of chemo, immunotherapy, having a non-viral approach for a patient. So, we probably would see more third or fourth line usage there. Okay. And one more, just on 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 roughly? Yeah, that is the. Okay. That is the patient number, right. Okay. If you think about it, 75% of the practices are community. Within that, detalimogene could be attractive to all 75%. Where 40% of the patients are, there are differential attributes of detalimogene that unlock that practice that other products just cannot do. Okay. That is a real differentiating point where something special like detalimogene can make a big difference. Okay. You touched on it, sounds like depending on practice setting and the patient, obviously, where detalimogene could slot in terms of treatment sequencing might be different. I guess, is there an overall profile you're thinking about? Will this also depend on where the patient's treated? Well, I think, like in multiple myeloma. Yeah. These doctors now have the opportunity to have a real dialogue with their patients, and it'll be very practice- specific and patient- specific. The combination will be something along the lines of, "I am sorry, Judah, your BCG is not working. Right. I have two or three. Here are the pros and cons of these agents." Right? "You have to come in every six weeks. If it does not work, it is another six weeks intense therapy. I am going to insert a device into your bladder. You have to be here every three weeks. You have to drink 1.5 L every day. You are going to feel that." Right? "Or I can start you with something like detalimogene where we are going to know within three months whether it is working. You come in week one and two, week five and six. It is very well tolerated. Yeah. 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? What is that thought process as it's evolving now? I think that's more in the realm of the academics. Yes. Right. So, the academics, because remember, let's step back a little bit. This is a disease. It's cancer. It's a very serious cancer. However, it progresses at about 20% over 10 years. Right. It is a slow cancer. It is also a cancer that is affecting, the average age is around 70, 75 years old. These are people that are getting a little older, and they have comorbidities. Generally, they are smokers. The treatment choices and objectives are different. How can we control this bladder cancer so the patient may pass from something else? For the academics, I think they like to go immunotherapy, chemo, immunotherapy, chemo. If one of these products is not working, then, I think the mechanism makes a big difference. Right. Non-viral 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? In both cases, detalimogene can be a useful product. Okay. You mentioned you think two, three, 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 willing to accept? Yeah. Market research says probably more than that, three or four lines of therapy. Given that a radical cystectomy is such a severe. Yeah. Outcome. In our payer research, if you have NCCN guidelines. Right. In general, you are going to be reimbursed. So, this is not a large barrier to uptake for detalimogene. Okay. I guess speaking of the competitive dynamic here on 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? In those payer conversations, do you have any insight into where pricing could head? The range in pricing for these products is $220,000 to about $700,000 a year. As we have had dialogue with payers, our payer research, goes back to what I said before, i t's cancer, it's serious. If it's on the NCCN guidelines, it's generally going to get reimbursed. Right. Okay. That's helpful. And what's interesting that it kind of changes the picture a little bit, because at the new benchmark pricing at $700,000. Right. That's 2,000 patients that you need to hit $1 billion. Right. Which when I talk to you about incidents of 20,000-40,000 patients per year, there's lots of room for lots of agents. Right. That makes sense. 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 quite viable for a company like ours to launch the product. We'll need about 40- 60 sales reps as a proxy. When you think about these community practices, these LUGPAs, say there's 30 doctors, 30 urologists, three or four are focusing on bladder cancer. Right. We're able to target those individuals with that sales. So, very much well within the abilities of a company like ours. Okay, great. 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, a t what point in the clinical or commercial kind of launch of the drug would this factor in? Yeah. So, when we designed detalimogene, we designed it for community urologists. Unlike other products, no pre-washes, very few installations, 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 pre-clinical 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 pre-clinical models, we see IL-12 expression going up as much as 10 times, w ith a pretty mild surfactant called polidocanol. We selected polidocanol. It is an approved drug. It has got a lot of safety information. It is actually used at up to 1% in a lot of shampoos. What we have done is to still, again, we are always trying to make our drug more efficacious and simpler. What we have done is we have 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. Right. This will be easier to hold it in. Very simply, what occurs is you put polidocanol in. Let it sit for five minutes with the catheter, take it out, 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. Right. 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 pre-clinical data is. We are already up and going with the cohort. We have just gotten through the safety run-in. So, w e will have data very soon, and this has been an important part of the urologists' armamentarium. Okay, great. We will look forward to that. So, maybe in the last couple 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. 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 has China gone? China used to be a place to go for manufacturing and manufacturing things very quickly and inexpensively. Now, they have just moved up the curve. Right. On innovation. Right. I think, for us specifically, as it relates to detalimogene, it has relatively little impact. Yeah. For us because we are so far along the line for commercialization. But as we consider business development and building out the platform, the technology that is available in China becomes very interesting. Right. For us. Okay. So, I really, at the end of the day, we are 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 on the early part of it. And wh en you think about AI, AI in our industry really started it in the discovery part. Yeah. Right? In identifying compounds, we've already developed a platform. Yeah. We've already translated the platform. Now, the AI is probably more about how do we commercialize. Again, there's a lot of interesting agents to help our commercialization. Yeah. 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's been doing. Okay, great. Last, we touched on it, but on the regulatory side, it sounds like FDA has been relatively stable in your interactions. 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 front, you're always wondering. Yeah. Because things can change, but I would say, even in the stormiest times, our stuff has been absolutely boring, w hich is fantastic. Yeah. Boring is good. Tariffs are again, something to think about, but again, as a company that's not commercialized yet, it's still around the edges, right? Unfortunately, as we commercialize, it's something we have to think about. And MFN, that's the one part where you think about a product like detalimogene really is an attractive drug for the globe. Right. Easy to handle, right? Right. 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. All right.