That's mid-biosec analyst. We're excited to have enGene joining us. 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. Thank you for being here. Maybe you can just start out for those less familiar with the enGene story. Can you provide a brief introduction to the company and your lead assets? First of all, thanks very much for the opportunity to be here. We really appreciate it. enGene is a company that has non-viral gene therapy, and that is unique. It's unique since when you first start and you think about gene therapies, you think about some of the shortcomings of gene therapies. In fact, by delivering gene therapy to the matrix, using our special Dually Derivatized Oligochitosan (DDX) platform, we've been actually able to solve some of those issues. First of all, we're able to give a big genetic cargo, so we're not limited by cargo. Our products are re-dosable, so we can use them over and over again as needed. Because it's non-viral, our manufacturing is a lot simpler, right? Our cost of goods should be competitive, which allows us to get to many more diseases. I think we sort of cracked the code in some of the challenges of gene therapy. From our platform, which is called the Dually Derivatized Oligochitosan (DDX) platform, our lead asset is a product called detalimogene voraplasmid. We're developing that for non-muscle invasive bladder cancer with carcinoma in situ (CIS). They're Bacillus Calmette-Guérin (BCG) resistant. That product is currently in a pivotal study, and we're delighted to announce it's very recently that we actually hit our target enrollment for detalimogene voraplasmid. It's a pretty exciting time for our company. Excellent. Maybe you mentioned the indication for detalimogene voraplasmid. Maybe we start with unmet need in bladder cancer and how detalimogene voraplasmid might address that unmet need. Bladder cancer is a pretty common cancer. It's the sixth most common cancer. It's about in the U.S., around 780,000 patients and about 82,000 patients each year. It's a growing population that's associated with aging, right? The current treatments, the base treatment is BCG, a product that's been on a chronic back order. Patients have a few other approved agents, but they often end up having their bladder removed via radical cystectomy. 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 and a response of NMIBC. If each of these competing programs, and we know one, will get to market, where does detalimogene voraplasmid fit? 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 with detalimogene voraplasmid and how that could impact you? First of all, let's talk about the needs of the urologists. Where are these patients? These patients are predominantly in the community. 70% to 80% of urologists are practicing here. Their needs are different. What we've done is we've designed detalimogene voraplasmid for the urologists, right? Based on our September data of last year, we demonstrated really good efficacy, 71% CR rate anytime, great tolerability. You pointed to the last point. Ease of administration equals beneficial practice economics in these types of practices, right? Based on that profile, we really believe that detalimogene voraplasmid is the product that community urologists will reach to first for all of those reasons. How does that compare to some of the other agents? 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? Current products have a CR rate between about 20% to 40% at approval. Frankly, I don't know how different that really is, right? It's such a small population. When you actually see these drugs being used in real life, you actually see better efficacy over time. I would say efficacy seems to be similar for these products. We seem to all be in the same range. What about tolerability? We demonstrated in our September 2024 data that most of our treatment-related AEs are associated with catheterization, grade one or two, 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. There's a risk-benefit for some of the other products. I would say we have a very competitive tolerability profile to check. The third part of the triangle is the ease of administration, which really equals practice economics, right? Let's think about these busy community urology practices, and many of these practices are focused in on how they turn patients through. If you compare detalimogene voraplasmid to the other products, there's no pre-washes, there's no special handling requirements, there is no co-medications required, there is no after-usage bleaching. You effectively, the patient goes in, gets the administration, and goes home. The number of administrations is relatively low as well. 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? Hopefully, that will mean that less patients have their bladders removed. Quite frankly, when you look at survey, the efficacy profile is demonstrated in the September of last year, tolerability profile, the ease of use and practice economics, it really lent itself to enGene being the product that urologists will reach to first. Okay. 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. What's your reaction to hearing that? How many community docs would kind of make the differentiation between detalimogene voraplasmid and handling BCG or a competing product? These are very different products, right? BCG is a bacteria. It's an older product that people know and the risks that go with that. Some of the newer products, which are very potent, are replicating viruses, right? I don't think it's the same. It's not the same. We'll obviously have to wait to see what the labeling says. For a potent replicating virus, in general, you need BSL-2 handling. You need a hood. You need a nurse that's willing to deal with the virus. 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. 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 re-ups? From our data of September of last year, as I said, we were pretty pleased about both efficacy and the tolerability. At the same time, we did it with one arm behind our back, right? We were not following any guidelines and standard of care for these patients, right? We implemented three important protocol amendments, and we believe that will help efficacy and be less an efficacy on the table. The first one being is most serious patients are T1 patients, right? Before, we would allow patients with T1 disease to have one resection, and they'd go automatically into the study. Now, the standard of care says you really should do two TURBTs, right? Make sure it's not there. The big difference for us is, if there's still T1, the patient will not be enrolled. If they have had their T1 removed, it's been proven that the second TURBT is therapeutic in nature. What should be the net? You get 14% of our patients that were T1 before. Our competitor, the other companies, are low single digits. We'll probably be low single digits, and I'll probably have patients with a better profile. That's one thing that should make a meaningful difference for us. The second is after three months, if there was a little growth, the TA, a papillary of some sort, we said to the doctors, "You have to take the patient out." The doctor said, "Everything else looks great. We just cut those things out." In fact, now we're allowing resection of TA and allowing those patients to be re-induced. That, for other companies, has made a pretty significant difference in efficacy as well. The third thing is that previously, when a doctor suspected that there was progression, they'd look in the bladder and say, "That looks red. It looks like it's progressing." We would allow them to have them leave the study. Standard of care says you can require a biopsy, right? We believe those three improvements—limiting the number of T1 patients, making sure we have the right T1 patients, allowing resection of TAs and re-induction, 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. 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, also as you outlined in the context of competitor data? A 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. It was chuckled. I would say, first of all, based on what I just talked about, about the protocol changes, I think the number one thing people are saying to us is, "Okay, will they make a difference?" That is where we're really focusing our energies on. Now, given that we made those protocol changes near the end of last year, we'd like to have a big enough cohort of patients, three to six months, where people say, "Okay, yeah, this looks like a difference," right? Given that enrollment had sort of ramped up at the end of the year, early next year, what we anticipated sharing for three and six months data, that'll be the real focus of what we're trying to do. We're waiting for that point where we have a good-sized number of patients where people say, "I get it," right? Yep. That's where we're focused. Where should investors be focusing on? To be honest, I think it's where do doctors focus, right? If I call the community urologists 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. No disrespect, right? Because it's not a focal point. What do they focus on? Does the product work or not, right? That is CR anytime, right? From my perspective, I got to look from a customer perspective. They're looking at, does this product work or not, right? CR anytime is probably the best proxy for that. Okay. That makes sense. A question that I think applies to you guys is not necessarily specific to you, but with some changes at the FDA and some surprise CRLs in this space, single-arm trials in oncology have been called out from time to time. I guess there are some investors that are uneasy. How are you viewing registrational path for detalimogene voraplasmid currently versus maybe in the prior administration? Any color you can share around just registrational path and confidence. Oh, we have a high level of confidence. You might have seen recently that we received that designation based on our September data. That, to me, suggests that the FDA sees the unmet medical need that I talked about previously. They're engaged. I also looked at the proxies for our engagement, and they've only been very supportive and engaging with us. I look at the draft guidance. Draft guidance came out in 2018. They reiterated draft guidance in the summer of 2024. 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. Based on that and based on recent approval, I think we feel pretty good about where we are. Great. 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? Yeah. We are getting ready. We've already made changes to get ready. I think, first of all, we're in the process already of writing many of the modules, right? We will be ready to submit as soon as we get the data. In terms of market preparation, you might have seen some recent announcement where we've added three board members that have been involved in commercial launches. We added a Chief Global Commercialization Officer who's launched dozens of products successfully around the world. We're starting to really dig into the market research and getting understanding of the different physicians because what's really interesting is just a bit of a paradox here, right? This is a disease that sits predominantly with community urologists. Community urologists are busy seeing patients' meds, right? They're also not really tracking the new medicines, right? 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 at three, four, five lines of therapy, where these community doctors are seeing de novo patients, right? What we've been starting to do is trying to quantify and understand their needs. In some of the early work that we've done, the profile of detalimogene voraplasmid based on our September data, efficacy, tolerability, and that's the ease of use and positive impact on practice economics, really makes them attractive. We look forward to sharing some of that data over time. Great. We'll look forward to that. The LEGEND study 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? Yeah. We have three 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're BCG exposed. The fourth cohort are patients, the others have CIS. Fourth cohort, no CIS, and just papillary. I think our thinking there is we're really trying to meet the needs of urologists, right? Trying to provide them as much insight into different patient populations so they understand the totality of the value, you know, of detalimogene voraplasmid. There is some precedent for some of these populations to receive some NCTM guidelines as well, which is also useful for what they're prescribing community. We've provided guidance to say they'll provide an update on those later this year, early next year. Some of that, quite frankly, the priority is in cohort one, right? Enrolling that's going to provide more insight on that as time goes on. Great. Is there any reason to think that commercial dynamics could differ materially in some of these subsequent populations versus your lead indication in terms of standard competing with standard of care or competing with other clinical players in the space? Yeah. I think there are some differences, right? We'll get an indication, and we'll obviously be promoting within the indication for the BCG resistant with CIS patients. However, the BCG naive patients, there's a lot of logic to the profile of the product we have. In a country where there is a problem with access with BCG, it becomes a viable alternative theoretically, right? Providing information on that could be interesting in a different dynamic, right? Obviously, the price point for BCG is quite different, right? The unmet needs are different in those spaces. The competitors' stats are a little bit different, but we'll be focused on promoting the BCG resistant patients, CIS. Okay. Makes sense. And then just on the Dually Derivatized Oligochitosan platform more generally, where might there be opportunity for enGene Holdings Inc. outside of bladder cancer? What can you share with us in terms of thinking beyond bladder cancer, or is that just, you know, laser-focused on it right now? We are focused, right? Below the line, you know, we're doing a lot of work, right? Our team invented this platform. We continue to do work on the platform. I think what we think about is using the platform, number one, you know, detalimogene voraplasmid, we believe it's a really interesting product, but we always want to lifecycle manage that, right? How can we make it even more convenient? How can we make it even more potent? There's some, you know, thoughts that we have on that. Secondarily, could we take it to some other cancers or in other forms of cancers? Certainly, there's a range of GU cancers where the profile of that product makes a lot of sense. Third, since we cracked the codes for delivering non-viral gene therapy to the mucosa, think about in your body where there is mucosa where we could have good dwell time. There's some logic for a product like ours or a product from our Dually Derivatized Oligochitosan platform. Now, you know, detalimogene voraplasmid is the beginning of the story. We continue some really good work that I'm pretty excited about. Over time, hopefully, as that matures, we'll be able to share more details. Okay. Great. 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? Yeah. The guidance that we've given is provided 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 2027. That's what's ahead of us. We're kind of in an exciting period. The nice thing is that we're well capitalized. We have a little over $250 million in cash, and based on our current plans, that gets us into 2027. I feel pretty good about our cash position. We feel pretty good about where we are from a development perspective, detalimogene voraplasmid. Okay. Makes a lot of sense. Maybe just last company-specific question before I get into a survey we're asking all of our management team. Anything we didn't discuss that you'd highlight around the enGene story? I think there's one point that we did not talk about, right? When you think about these products and getting them launched, manufacturing has been an issue of course for these products in general, and particularly the ones, you know, just viral products in general. I think this is 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 voraplasmid is really four ingredients, right? The ingredients that are readily available, and you know, with those four 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, and they are looking very good. I think we feel really confident in our ability. There's always work to be done. Some caveats, you never know exactly. I think we feel pretty good about wrapping up our manufacturing CMC module, even before the clinical data comes, right? When the clinical data comes in, putting together our filing package should be pretty straightforward. 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 three thematic topics. The first one is on China. With China's rise in biotech innovation, how are you thinking about your competitive position here? Will this influence your R&D or business development strategy? I think, first of all, the proliferation of new agents and technology from China is a good thing because more good drugs are good for patients overall. I think we sit in a unique position. Our Dually Derivatized Oligochitosan (DDX) platform is proprietary, and it's taken a long time, actually, to build that. I don't feel very, you know, not that concerned about that. Of course, from a China perspective, as we go forward from this development perspective, it gets interesting for us as well, too. I think it's a real opportunity for us. Okay. Great. 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? I, in general, think that AI is really going to be a boom for our industry, right? If you look at it at the various different stages, I think the discovery folks have probably been using a form of AI for quite some time, actually, right? It's just gotten better and better. We'll 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 the same stage as the development folks, starting to dabble into things around the edges that are moving our commercialization. I think the last part in the GNA functions, particularly in working with our vendors, this is going to be an opportunity to reduce costs, actually. I think as we go, and you already see that, right? We're not a commercial, but I can see some of the things that traditionally we would pay a lot of money for, AI will replace. That will actually help us with our commercialization. Overall, I think AI is going to have a pretty big impact on the totality of our industry. I'm looking forward to seeing it in sort of these latter stages and how it begins to help us. Great. The last topic that's been most relevant to most of our Smithcap biotech companies is on the regulatory side of things. We didn't touch on this specific to enGene, but changes at the 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 of things now as we contemplate filing for, like, right. You know, we already talked about the fact that we have RMAT, the fact that there's already guidance. I think, to me, the most important, what do I look at from the regulatory perspective? I look at, number one, how responsive is the FDA? Number two, do we have consistency with individuals? Those are the soft parameters I look at. We have the same project manager, and that project manager has been really engaged. Number two, the FDA has been just terrific. They've been right on time or early on things. I mean, they're very responsive to us. I think from a regulatory perspective, we feel pretty good. We're actually grateful for the support from the FDA. On the other two, being a pre-commercial company, there may be things that are down the line to think about, but they're not really impacting issues for us right now. Okay. Really helpful. I think if there are no questions in the room, we will leave it there. Thank you again for the participation. Really appreciate it. Pleasure to be here. Thank you.