Great. Thanks everyone for being here. My name is Yanan Zhu, and I am one of the biotech analysts here at Wells Fargo. It is my great pleasure to be joined by Ron Cooper, CEO of enGene, here to talk about some of the company's updates. Thank you, Ron, for being with us. Well, real pleasure to be here. Appreciate the invitation. Great. I was wondering if you could start us off by giving a quick overview of the company, the initiatives. Yeah, sure. So, enGene is a public company. We are focused on non-viral gene therapies, so very unique platform that we have. It is a company that is well advanced. Our lead asset, detalimogene voraplasmid, is a non-viral gene therapy that we are developing for a form of non-muscle invasive bladder cancer, those patients that are resistant to BCG, who have carcinoma in situ. Our clinical development program is called the LEGEND program. It has multiple cohorts. The pivotal cohort is one of the largest in this space of 125 patients. And we are at a very exciting period for the company, where we expect to have that data maturing near the end of this year. We expect to meet with the FDA later this year, and we plan to file by the end of this year and expect an approval next year. This morning, we announced our quarterly. We have $266 million of cash, and that gets us through all of those things. We are a company that is well capitalized and that is poised for a real growth period. Great. Thank you. Let us focus on LEGEND. You released interim data in May. As you said, you will have another readout, I think that is probably the final readout, right, later this year. Could you start by reviewing for us the data that you obtained so far, and then we can talk about the expectation for the upcoming data? Yeah, sure. We are a public company, we are also a Canadian company. Our disclosure requirements are different. The LEGEND Cohort 1 study is an open- label study, and we provided a data update in May, which from our perspective, the market grossly overreacted to, and I will tell you why. First off, when you think about these products, the primary endpoint is complete response rate at any time. We displayed a 54% CR at any time, which is in line with all the other approved products. That is the primary endpoint. Secondary endpoint is of those 54% of patients, what percentage are durable at the 12-month time point? If you look at the products that are approved, it is a pretty tight range, about 40%-50%, so let us call it half of the patients. We had 21 patients that were complete responders that had not progressed to that point. It is a little bit early for us. Another endpoint that is a Wells Fargo focus is 12-month CR landmark number, and at that time, we had, again, immature data, but projected to have around 25%. That is the efficacy part of it. That is always just half of the story, right? The tolerability part of our medicine is really important. 80% of the patients are in community practices, and community doctors really want to have products that are efficacious and tolerable and easy to use. Our tolerability continues to hold even with more exposures. For example, our treatment interruption and discontinuation rate is very low, 2.4%, where many other products are in double digits or high double digits. I think we shared what I consider to be a pretty solid data update, where our CR at any time, the primary endpoint, is in line with other products. Tolerability, in line with other products, but probably best in class from that perspective. An immature durability data set, which we will hear more about in the fourth quarter of this year. Got it. For the fourth quarter data, sounds like clearly there will be more mature 12-month landmark CR data. Any other incremental learnings do you think we could get at that readout? I think there are a couple things that we are looking for in the fourth quarter. First of all, CR at any time was almost finalized by that point. That will be finalized, right? The durability, the percentage of those patients that are durable 12 months and beyond, we will have some more data on that, but probably not all of that data. The 12-month landmark number, we will have the majority of those patients, but we will have that information. Hopefully around that time as well, we would have had an opportunity to meet with the FDA, and we will have some insights from our pre-BLA meeting. Got it. Yeah. I think you alluded to this earlier. How do you see detalimogene positioned in the high-risk, non-muscle invasive bladder cancer space? How does the data support that positioning? I think you spoke from the safety tolerability perspective. Could you help us take a look at the landscape and help us elaborate on where you think you have an edge and can fit? Yeah. Our market research suggests that detalimogene will have a very strong position within the NMIBC high-risk space. Why is that? First of all, when you look at the marketplace, let's call it 20% are in the academic space, 80% are in the community space. The needs of each of these groups is different. In the academic space, they're getting patients that have been through multiple lines of therapy, been sequenced, and have landed up probably more serious disease. The academics, in general, would prefer to go to radical cystectomy because removal of the bladder has a 100% CR rate, right? It's easily accessible to them. But most patients don't want to have organs removed, right? Radical cystectomy for an average patient who's 75 years of age, it's a pretty heavy surgery. It has high mortality and has high morbidity. Multi-organ surgery from a morbidity standpoint, you land up with an ostomy, you land up losing a prostate, you probably lose sexual function. So it's a big surgery, right? But that's the domain of the academics, and there's some products that lend themselves to the academics. If you go to where the patients are, where 80% of the patients are, the community urologists are screaming for new agents that they can use easily. Right now, they get BCG if they can get it. They use chemo, gemcitabine off-label. Recently INLEXZO has given them a product that they can actually use. So that's pretty exciting for them. Where we see detalimogene is the first non-viral gene therapy. It's unique. The reality of it is we're going into a world with multiple options where sequencing for community urologists can actually begin, and that's going to start building the prevalent population as well. When we do market research with community urologists, they say to us what do they want. Well, they want efficacy, and we have efficacy with detalimogene. They want something that is tolerable for their patients. We're trending towards best-in-class tolerability, and they want something that slides into their practice flow easily, and we probably have best-in-class in that area as well. So we really believe there are some unique segments within the market where detalimogene will be preferable compared to other products. Got it. I think you just talked about what community doctors want, right? I think that's a very good framework. On ease of use and sliding into their practice, this one you have the best- in- class, right? I think you just stated. On safety, is that also among the best? Would you say that's another strength for detalimogene? On efficacy, I was wondering, you mentioned these doctors do want efficacy, right? On what level, and how different are community doctors compared with academics when I guess both of them will want efficacy, but how are these two different, and what are investors missing? Can you help us understand? Well, I think it's the combination of things, right? Many of us take medicines or family members take medicines. What do you want? You want a medicine that works. You want a medicine that doesn't cause a lot of side effects, and you want a medicine that's easy for you to take. That's pretty general, right? If you then think about the attributes that detalimogene have, we offer all three of those things, and there's not one product that gives all three. We're the only one that gives all three of those attributes. That's the first point I would like to make. The second point that I would like to make is that when you go to these community urologists, right, let's think about what they're faced, right? They are in areas with not as much infrastructure. They're stretched for the number of urologists. They're under pressure from their owners, private equity. They want to deliver very good care, right? What can a product like detalimogene allow them to do? It is easy for them and easy for the patient, right? Right now, our market research says that they want efficacy, tolerability, and ease of use. The detalimogene journey is one of the patient comes back and the doctor would say, "Sorry, your BCG isn't working. I'm going to start you with detalimogene." And literally, that doctor will walk out of the office. Someone from the staff will be able to reach into the fridge, mix it with water, instill it. In the clinical trial, we keep the patients there for an hour, but in real life, they don't have to do that. They will then say, "Go home, hold onto that for an hour, and just void it into the toilet." Right? That is really easy. Versus there are other medicines where you have to schedule a drop shipment in. There's a long thaw time. There would be multiple pre-washes that the patient has to have, and then there's much more intensity of the treatment. If it doesn't work, if it's the first six weeks it doesn't work, then another six weeks. And then there's precautions, and even for INLEXZO, you see these precautions, right? Where you need to wash clothes separately, use separate restrooms. If you spray or leak, clean up. You need to bleach your urine. We don't have any of that, right? What does this mean for the experience, both for the practice and for the physician? Detalimogene slides in quite easily for both. Okay. Got it. Yep. So then, I think you mentioned 20% of the patients are being seen at academic centers. For these places, are you saying that detalimogene 's main area of focus is in the community doctor space, right? The academic center is not necessarily something that you want to compete in, right? Yeah. What is interesting for us is we are starting to get more sophisticated in our market research. Everybody first says, "Well, it is just this big group of NMIBC patients." Then it is a big group of community patients and academic patients. We started to even segment within the community practices for ones that have attributes or needs that fit very well for detalimogene. So our feeling is that we will penetrate more in the community and even in some subsets of the community. For academics, I think, the detalimogene profile is more of one that fits in as being something different, right? Because what they tend to do is, if a patient does not want radical cystectomy, they will give them an immunotherapy, then a chemo, an immuno and a chemo. We would be the only non-viral gene therapy. We would probably expect later line use in the academics, not earlier line use where they would want to have something new. So the majority of our business should come from the community urologists and from some particular segments, but we will still have a significant portion of business from the academics for a different reason. More because it is a unique non-viral gene therapy. Okay. Got it. For the academic center, I think these are the doctors who really care about 12 months CR rate. As you were discussing, your data were not quite as mature at the interim. For the final, is there necessarily a bar of 20%, for example, or a different bar? Or I think your Kaplan-Meier estimate is 24.5%. Do you think your actual data will come out similar to that? Or if that is the case, then why is that the case? Because I think for some other companies, the Kaplan-Meier curve estimate may not necessarily be what they later produce. Yeah. I think, first of all, when you start looking at these agents, it is exciting for doctors to have new agents, right? I think we are getting a little bit too caught up, though, in the reality that these studies are tiny. Right? We have the largest at 125. Some are as small as 70. If you really put them on top of each other, probably the error bars are on top of each other. Right? When we get into real life, I am not so sure. A lot of this will start to wash out, and in real life, it will be really about, does the patient tolerate it? What happens with individual patient in individual practice? As it relates to durability, in our April update, the Kaplan-Meier curve said we would get close to 25%. But remember, within that database, we have all of the non-CRs, the non-responders. We have 21 patients who are CRs. We just do not know how long they are going to progress. The Kaplan-Meier is overweighted by those non-CRs. That is the majority of the data. I think, we have to see how the data progresses, but we feel pretty confident that we will be in the Kaplan-Meier range. That would be similar to other products that have been approved. Got it. In terms of the framing that these are small studies, error bars largely overlap, I guess that also applies to anytime CR, whether it is I do not know, would you consider 54%, 55% different from 74%, 75%, for example? I do not in real life. Right? What folks forget that that is the primary endpoint. That is the one the FDA would look at. We are right in the range of others, right? I actually see very little differences in these small databases. I think what is going to happen in real-life usage is individual patients will respond to different technologies. Doctors will have the luxury of having individual products. The nice thing about detalimogene as our product is that there are two things. For the responders, that usually occurs within three months, so they know very quickly if the patient will respond or not. The other flip to it is then on the risk part of it is the progression is 3%, very low, right? It is a little bit of progression, right? The risk-benefit for a doctor to use a product like detalimogene early is very low, well-tolerated, easier on the patients. You are going to know very quickly if it works. If it does not work, you are not going to do very much in the way of harm. Okay, got it. Let us talk about regulatory path and filing. Have you had any recent interaction with FDA, especially on the point of what patient population or subgroup to include for the pivotal data set? Yeah, we have a lot of interactions with the FDA, and in terms of the statistical analysis plan, that is a back-and-forth process, right? That will take a while to finalize. We have not finalized that as yet with them, but we do know of the 125 patients that we have reported, our final number will be a subset of that. Right. Given that you are planning to submit BLA second half of the year, is there a pre-BLA meeting scheduled? Also just in general, what has been the area of focus in your interaction? Yeah. We announced this morning that we are on track for pre-BLA meeting the fourth quarter of this year, so we are pretty excited about that. I think when you think about the modules that go in, just to give you a perspective of things, the manufacturing module is probably 5x- 8x the size of the clinical module. In fact, having RMAT designation and CDRP allow us to have a lot more dialogue with the FDA. The nice thing about our product from manufacturing perspective is we have totally completed our PPQ or FDA validation runs. CDRP allows us to really open up our dossier to them early, and they give us feedback on, they want this, they want that, they want less of this. That is probably the biggest focus of our dialogue with the FDA, to make sure that we are on track from a manufacturing perspective. I think you know that most CRLs of late have been for manufacturing, not for clinical. Particularly in this category, that has been an issue. That is going to be a real advantage for us because we should have low-cost manufacturing, low cost of goods relative to the other products. With CDRP and RMAT, we have had a really robust dialogue with the FDA, and I think we can provide to them what we want. I think that minimizes the risk in that space. Okay. Got it. Maybe looking ahead for potential commercial opportunity, I think we talk about this community offices kind of a focus. I think at your investor day recently, you talked about 8,200 patients in, I guess, every year in a community setting, right? You also further carved out 41% being, I guess, the most addressable opportunity for detalimogene. Can you talk about that level of focus, and help us understand what might be your penetration, your positioning in that very specific group? Yeah. Let me just correct that a little bit. If you think about it, what we believe is the incident population is around 20,000 patients per year. Some would say it is as high as 40,000, depending how you define that incident pop. So there are enough patients there. The numbers that you were quoting, the 41% and the 8,200, that is a subset of the incident population where we believe the detalimogene profile is particularly attractive. For instance, in our segmentation, we identify a group of practices that are called resource-constrained practices. In a resource-constrained practice where they do not have a -80 fridge, a BSL-2 hood, do not want to purchase a bunch of PPE to administer the product, or do not have a nurse that will handle a virus, right? That type of practice is really ripe for a product like detalimogene, right? Where any qualified medical individual can administer detalimogene. Detalimogene will sit in a regular fridge, a freezer for many years, probably, and multiple months in the regular fridge. Again, I think we define the market opportunity overall about 20,000 to 40,000, depending on the definition. 41% of that we think are really super targets for detalimogene itself. Super targets. So it is 41% of the 20,000. Yes. Not of the 80,000, right? Yes. Roughly about that. Of the 8,000. Right? Yeah. Yeah. Okay. Got it. Okay. Thank you for clarifying that. Can we also touch on reinduction? I think you touched on it when you talk about the competitive landscape, some other therapies require reinduction. How do you think about reinduction? I think the rate of response in the LEGEND trial is like 14%. In light of that, in the commercial setting, do you anticipate there will be reinduction use or essentially there shouldn't be reinduction use? Yeah. Unfortunately, that word reinduction is used a little too loosely, right? For other agents where you get the medicine six weeks in a row, if it does not work, then you get another six weeks in a row. That is a very intense therapy for the average age patient, 75 years old, right? The way to think about detalimogene is we actually reinduce through the whole year. Right? When you think about it is, because you get detalimogene week one and two, week five and six, right? Rinse, repeat for three more quarters. Then you go into a maintenance phase, right? So it is a very different approach, and that is deliberately designed for community urologists and patients in the community. As it is, these patients are frail patients. They have gone through a tough course of BCG, depending on how it is administered, right? The idea being is that then you go to detalimogene. Week one or two, you take a break. Week five or six, then you take a break, and you spread it out over time. We do anticipate that doctors will go through that phase of induction, reinduction before they get into the maintenance phase. I see. Patient who are not responding after the first three months of treatment, Yeah. they just go on to receive additional therapy. Yeah. They would get the three-month treatment, then the six-month treatment. I think there's a big difference in real life versus the clinical trial. For us, at the six-month timeframe, if there's a lesion, a growth of some sort, the patient comes out of the trial. More likely than not in real life, that lesion will get resected and they'll just continue on therapy for the patient, right? Again, we've got to be careful of these small trials, heterogeneous patient population, heterogeneous protocols versus real life. I think in real life you'll see detalimogene usage be a lot different. Okay. Got it. Maybe just in terms of lines of therapy, right? How many cycles do you anticipate patient to go through bladder sparing treatments, right? I think I hear you, if I interpreted this correctly, in a community setting, detalimogene probably earlier in the line. In academic setting, maybe later in the line. Do you view the different lines of opportunity as roughly the same, or it greatly diminishes as you go line after line? To answer your first question, our market research suggests patients will get three to four lines of therapy. I think what Wall Street is missing is that that's occurring in the academics. It's not really occurring in the community yet because they don't have the right agents for that. So we're going to see a boom of sequencing and a boom in the prevalent population. Then you say, "Well, do you have to be first, second, or third?" I don't think it matters that much, to be honest. If you look at our study, in the LEGEND study, about a quarter of the patients have prior therapy before, other than BCG. We are still showing overall pretty good efficacy numbers. Given that these patients don't progress very-- They progress very slowly, but they reoccur relatively frequently. All the agents have about a 40%-50% reoccurrence rate at 12 months. We're going to need new medicines. Got it. Let's talk about the surfactant cohort. So obviously, you started this effort recently. Can you talk about why you're adding a step? You have talked about convenience and that for a while, but this is an extra step. Help us understand that. Yeah. The design principle for detalimogene is designed for community urologists. Unlike other agents, no pre-washes, nicely spaced out installations, nice and easy, and no post-treatment actions to take, right? That's the design principle. With that, you see that we've shown great efficacy, best-in-class tolerability, best-in-class handling. We had always thought about using a surfactant bladder rinse for some other indications, but we wanted to select the right one. We know that other gene therapies have used a surfactant bladder rinse, and if you look at their preclinical data, there's very little transfection without a surfactant bladder rinse. Whereas with detalimogene, without a surfactant bladder rinse, we actually get pretty good transfection. If we add the surfactant bladder rinse, we get both greater depth and breadth. IL-12 expression increases around 10x. We're pretty excited about that. We wanted to select the right bladder rinse, though. We selected polidocanol, which is a readily available product, lots of safety behind it. We also wanted to see if we could find a way to make this more convenient to patients. Right now, the dwell time for our agent and other agents is an hour. We're going to cut that dwell time in half, making it easier for the doctor and for the patient. It'll help with the flow of patients. Also remember, these are average age 70, 75-year-old patients. Incontinence is already an issue. The ability to hold it in is a difficulty. Reducing that's going to be a big patient benefit. The trade-off is, it's a short five-minute installation of the surfactant. The patient gets catheterized, five minutes of the surfactant. Removal of it, then you add detalimogene, and then you tell the patients to hold it in for half an hour. Overall, it's a net savings of 25 minutes for the patient. We think at the end, more efficacy, hopefully, and durability. We'll see how the data, 25 minutes saved for the patients in the practice, that's a net win. Great. Can you then explain the design of the surfactant cohort and give us any update that you might have for that effort? Yeah, the surfactant cohort is very similar to Cohort 1, so it's BCG unresponsive patients, high-risk patients with CIS. Because polidocanol, while it's been used in other diseases, it's approved, we've not put it in the bladder. If you look at our preclinical work with polidocanol, looks very well-tolerated, very little to non-systemic exposure. However, like a proper company, we want to be cautious with patients, so we just recently completed the safety run-in, and I'm delighted to report, we reported this morning that there were no dose-limiting toxicities. That's really great news for patients and for the trial itself. Now it's a matter of now starting to recruit patients and generating the data of detalimogene plus the surfactant that will sit beside the detalimogene on its own data. Will this then become an sBLA situation, or will you need a separate trial for this setup? Yeah, I think what we anticipate is we expect an approval for detalimogene on its own next year, and we'd like to shortly thereafter follow up with a supplementary with this data. I think at the end, right now we're tracking towards best-in-class tolerability, best-in-class handling, best-in-class cost of good, and in-class efficacy with the surfactant and detalimogene, and we have the potential to have all of the above, best-in-class product. How big is the surfactant cohort? We're still in dialogue with the FDA as to the size of that, so that to be determined. And- We can enroll up to 85 patients. And you would expect the efficacy to be greater than the current regimen or not? Any expectation along that lines? Well, the preclinical data shows that you get greater expression. In the mouse model, what we did is we took a subtherapeutic dose of detalimogene. With the subtherapeutic dose, we had subtherapeutic efficacy. We added polidocanol, and bang, the efficacy went right back up. So we have to see what the data says, but we would anticipate greater efficacy and potentially better durability as well with the combination of surfactant and detalimogene. But as it is, detalimogene on its own has demonstrated good efficacy, great tolerability, and great ease of use. Got it. Great. I think with that, we're out of time. Thanks, Ron, for a very enlightening session. Enjoyed it. Thank you, Yanan. Great. Bye-bye. Thanks.