All right. Welcome. My name is Michael Schmidt, Senior Biotech Analyst with Guggenheim. Let's fire up our enGenes. All right, pun intended. Welcome to this next fireside chat with enGene. With us, we have Ron Cooper, CEO. Ron, welcome. Thanks for joining us. Yeah, thanks. Thanks for the opportunity to be here. Good to see you, Michael. Great timing this morning with the news announcement, and we'll talk about it in detail. Before we get to that, maybe just remind us of the value proposition for your lead product candidate, datolimogene hayemab, and how it compares to others in this space. I think it's a really exciting time in just the bladder cancer space, in the NMIBC space. When you think of what standard of care used to be, it's BCG, more BCG, a bunch of experimental things and take someone's bladder out. Now, with FDA guidance, there's going to be a number of new agents. What does that mean? Think about whether it's your uncle or your father or grandfather. These are 75-year-old men, in general, who have a lot of comorbidities, have a lot of doctor's appointments. They don't really want to lose their bladder. These agents now will be sequenced, and we really believe that means the market is going to really grow. The first value proposition is we're going to come into it, I think, a market that's going to explode. The second thing then is that when you think about, I think my dad, a little bit cranky with all of these medicines and all the things that's going on, what is he going to want? He's going to want something that works, that doesn't have a lot of side effects, and that is easy for him to take. When you think about datolimogene hayemab, our profile is really that triangle. It starts off with efficacy. We just shared some information this morning that in patients in this new protocol, that we're showing a pretty competitive emerging efficacy profile. Second thing is our tolerability profile continues to trend into the best in class with very few treatment interruptions. Then three, because it's unique, it's non-viral gene therapy. The handling is easier for the doctors. It's easier for the patients. There's no pre-washes. There's no post-treatment extra things they have to do. You put that all together, the value proposition of datolimogene hayemab is unique compared to those new agents. It really lends itself to being the first choice, first line agent. Right. Are there big differences how NMIBC patients are managed in academic centers versus the community practices? There really is a big difference, right? Because in the academic centers, what are they getting? They're getting patients that have probably had two, three lines of other therapies. They're getting patients where the disease is advancing. Quite frankly, they would probably prefer a radical cystectomy, removal of the bladder, because that has a 100% complete response rate. Many of these gentlemen do not want that surgery because, A, there's a risk of mortality that goes to it, up 5%-10%. The morbidity associated is pretty serious. You'll end up with an ostomy and a stoma bag. Because the prostate is removed, you likely will lose sexual function. Their focus is the patient wants something, give me something that is the most efficacious. I have a big staff around that can manage side effects or handling, no big deal. You go at the other end. If we're in the middle of the United States and the urologist by himself, they have this patient here, what is their incentive? They really would like the patient to be happy with them, and they'd like them to stay within their practice. When you look at market research for what those urologists are looking for, it's really a combination of, and it's almost at the same level of tolerability, of efficacy, and how it slides into their practice. Datolimogene hayemab, given the competitive efficacy profile that we're showing, great tolerability and ease of use, really fits well in that community. Maybe with that, I know you've made an announcement this morning. Just give us a quick overview of the data that you announced this morning and yeah, just talk about that. I think the first thing that we announced, we're delighted that we've actually completed enrollment in the Legend Pivotal cohort. We completed the enrollment at 125 patients, which was above what our target was. That was really driven by the investigators. The interest was pretty high. Twenty-five patients are 25% more. That's very exciting. As a result, our database will be the largest database in this patient population across all the companies that have been approved or in process. That first is pretty exciting. The second thing is that we provided a data update last fall. At that time, we felt that the patients that had been treated up to that date had not been treated at standard of care or in the same way the AUA guidelines were. We implemented protocol amendment. Within that, there were three amendments that were particularly important. We felt that that would help efficacy. In fact, we showed today that at the six-month rate, we had a 62% CR rate. That is very comparable to the agents that have either been recently approved or are in the process. That was pretty exciting. That was a pretty significant increase from what we shared last fall. Right. Maybe talk a bit more about those protocol amendments and what exactly was changed and how the study now compares to what others have done in this space. There are three protocol amendments, and they align with standard of care and AUA guidelines. The first one is in regards to patients even before they get into the study. That is with T1 disease, with cysts. T1 disease, those patients, T1 cyst patients probably have the poorest prognosis. The standard of care before you put them into therapy is to do two procedures, two TURBTs. One, remove the papillary lesion, and then two, make sure it is all out. Previously, we were allowing them to just do it once and put them into the study. Now we ask them to do that twice. If there is T1 still present, they do not go into the study. If they do it successfully, then they go into the study. We also know that that second procedure has a therapeutic benefit. We anticipate that the patients that go in would have a higher chance of success. That is a pretty meaningful protocol amendment. That is even before patients get it. Second is, at the three-month time frame, we had doctors saying to us, look, it does not look like the cyst is progressing at all. The patients are doing really well. There is this little growth, the Ta growth. Previously, we would not allow them to remove that Ta growth, but standard of care is to cut that growth out and re-induce the patients. Now we are permitting that. Again, that is a material change. As you said, other companies have done something similar, and that has resulted in a pretty significant improvement in efficacy. The third thing is really about knocking out subjectivity and being more objective in our measurements and the longer term. Previously, we would allow physicians to look in the bladder and say, it looks like there's progression here. We will take them off therapy. That was a visual inspection. You can appreciate that's subjective. The bladder, these are being not bladders. You can see a lot of different things. Now we ask for a biopsy to confirm. Three changes: T1 before, Ta at three months, and requiring a biopsy before a patient comes in. I think that brings us into standard of care. I think you see that in today's numbers, that the protocol changes and the way we've been executing the trial have resulted in improvements in our CRs. Right. Are those criteria similar or the same compared to what others have done in the space recently? It's hard for me to say that because we don't have their protocol. Given that these changes align with standard of care and AUA guidelines, I would surmise that they would be close to that. That makes sense. Yeah. You obviously saw that nice improvement in the six-month CRA. Can you discuss the CRA at any time? It came down a tiny bit. Also, the change in the primary endpoint in the registration cohort from the 12-month landmark outcomes to the best CRA at any time now? Yeah. Let me take the second part first. We had a dialogue with the FDA. We've really enjoyed a good collaboration. We really appreciate their support. We just aligned on the primary endpoint being the same as the other agents that have been approved. That's the CR rate at any time. That's in alignment with other approved products. For the number itself, that's a very sensitive number. We anticipate that number is going to move up and down. If you even look at the confidence interval, it goes up as high as 74%. The reason that that's sensitive is that you could have a complete response either at three months or six months. Patients are still flowing through. Right now, we would have 57 patients that still have to go through. I think we feel pretty good about the six-month rate, the anytime CR rate of 63%. That's in the ballpark of the other agents. We do anticipate that moving around with the 57 patients that are still flowing through, but with the confidence interval that I've shared with you, I think we feel pretty comfortable that we have a product that's active and hopefully will be approved. Right. What do you think is the approval bar, if you will, for the best CR rate? What about duration of response? Yeah. Again, I don't want to speak for the FDA, but all I can do is look at the other agents that were approved. Remember, the first thing the FDA always looks for is safety. That's the number one role. I think for us, given the low rate of treatment-related AEs at 42%, which seems to be trending towards best in class, very low treatment interruptions, less than 2% relative to others, which are 30% or 40%, those are really good indications of tolerability. That's the first thing they look at. The second thing is the primary endpoint. We've already discussed that CR rate any time. Relative to the products that have been approved, we are definitely within that range. I think we feel very good about that. There are always going to be secondary endpoints. Some of those are duration therapy and the like, and we'll sort that out over time. I think we feel like we're in a very good position. Right. How does the tolerability profile compare to others? Right now, anecdotally, when we talk to our investigators, they say the patients don't really notice. It's a very small volume. It's 50 m. They almost say it's like saline. If you look at our treatment-related AEs, they're mostly associated with catheterization. Remember, these are bladders that are really beaten up. Mostly grade one and twos. If you look within the study itself, very few patients have discontinued. Very low rate of discontinuation. Very low rate of treatment interruptions, 1.8%, where the other agents are in the 40s and the 30s. What does that mean? If you dig underneath that, that means that when people take datolimogene hayemab, they're taking it on time. They're not delaying. They're taking the therapy, which really speaks to really favorable tolerability. We're really encouraged by that profile. When we were talking about these community urologists, when they think about these products, they really think about tolerability, efficacy, and how it fits into their practice. This is going to be a big driver of use. Right. As you noted earlier, you did complete enrollment of the Legend study. Yeah. What can you tell us about timing of the top line data and then subsequent FDA submissions? Yeah. We're excited to have enrolled the Legend Pivotal cohort and actually over-enroll that. We anticipate two things happening in the next little while. We're going to be having a dialogue with the FDA. Like any company, once you finish enrolling your pivotal program, you have a dialogue with them on the statistical analysis plan, SAP. We'll go back and forth with the FDA and make some proposals. They'll come back to us, and we'll probably agree with something as we get into the new year. That will give us a bit of clarity on which patients are going to be in the final analysis. Obviously, they'll make the decision at the end, so that's subject to change. That's job one. At the same time, we want to make sure that while our data is very promising at that six-month, and we've got a few patients that are at the nine-month that have looked pretty good as well, we'd like to share with folks some of the longer-term data. In the second half of the next year, that combination of those two things, we intend to share with all of you. Right. How important is the 12-month CR rate at this point, given that the regulatory endpoint is the best overall response, right? In terms of demonstrating durability, how important do you think is the 12-month CR outcome? It's hard to parse out one thing versus the other. The reality is, we interact with the FDA many times. They look at the totality of the data, so all of this stuff is important. As I say, tolerability first, primary endpoint. Durability is going to be a secondary endpoint. It's obviously important, and we will add that. I would argue that particularly with this patient population, this is an elderly population with multiple options. As long as if they recur, they can go from medicine to medicine. As long as they don't progress, durability is always important. In this case, with multiple options, these patients are going to be treated a lot better than they were a decade or two. That's for sure. There's been some discussion of manufacturing process, CMC for some of the other products, and the regulatory aspects of that process. Where are you with your manufacturing process and supply chain and some of the CMC activities that need to be done? Yeah. I think that's really an underappreciated strength of our organization. So having a unique non-viral approach allows us to manufacture using four simple ingredients in no special circumstances. We've been manufacturing at scale for quite some time. We're pleased to report that we're nearly through our FDA validation runs or PPQ runs. We anticipate starting to draft that module, CMC module, later this year, early next year sometime. That should not be a gating factor towards our filing. What is that going to mean from a market perspective? Obviously, we'll work with the FDA. We have the RMAT designation, which helps us to ensure that we reduce the risk of any CRLs. That's pretty important. We'll continue to dialogue with them. When we get to the marketplace, given our relatively low cost of goods, that's a competitive advantage for us because we can look at the marketplace and really thread the needle from a pricing perspective. We probably have more flexibility than most. We feel like we're in a really good position from a manufacturing perspective and a cost of goods. Right. Obviously, there has been a new product priced in the market recently. Is that a good analog? Is that a new benchmark for new products in high-risk NMIBC, in your opinion? Yeah. I don't know if it's a new benchmark, but it gives you sort of the range, right? The newer products of orders of magnitude or 200-ish to 600-700-ish range, right? That's a wide range. I think for us, that shows that this market is going to be a very large market because that suggests that that's what the value of these agents are. Given our cost of goods and our ability to manufacture and given our emerging efficacy and tolerability profile, I think that we'll be very competitive, and we should be able to thread the needle between that. It'll be interesting to see how this evolves. We'll make some good decisions if we're so blessed to be in the situation of where we're launching this product. Great. Thanks. I know you're looking into other opportunities as well with datolimogene hayemab. You have other cohorts enrolling. Remind us of some of those activities and which potential extension opportunities are available to you. What's great about datolimogene hayemab is that it's a product that we're studying in high-risk NMIBC-resistant patients, but it can be used in a wider range of patients and perhaps even used in a wider range of diseases. We continue to do work in the background that we hope to share with you over time. In the meantime, we have three cohorts that are ongoing. One cohort in naive patients, one in BCG-exposed patients. These patients, both, they have cysts and then one papillary disease only. I think what we're trying to do is generate more information so that physicians have a better view of the drug overall and kind of characterize it in some different patient populations. We look forward to providing an update as those data mature. Right. If we fast forward to perhaps next year, subsequent to filing, how do you think about commercializing this in the U.S. and perhaps the rest of the world? Yeah. So we're already doing a lot of work right now on what our go-to-market strategy looks like. I think at the highest level, I think our plans are in the U.S., we are ready to go at it alone. When you think about the target audience, let's say it's anywhere from 40-50-ish sales representatives, which is manageable for a company like ourselves. As we think about Europe, we believe there's a path forward in Europe. I have run a European business before. Our Chief Global Commercialization Officer has a lot of European experience. It may be viable for us to do that, but we will look at the economics versus a partner or not. The rest of the world, we will likely partner. All of that should help generate revenue. From a commercialization perspective, we've already started a lot of the work, particularly market research, market shaping. We hope to share with you some of our insights in the market research as it matures. Okay. Then lastly, just remind us of your cash runway and how far it takes you in terms of some of the upcoming milestones. Yeah. We feel really good about our cash position. From our latest reports, around $225 million, that gets us into 2027. As I've spoken before, the things that are ahead of us is long-term data update post-FDA discussion plus the filing. I think we feel pretty good about where we are. Great. Thank you, Ron. Really appreciate it. Thanks. Appreciate the opportunity.