For our next presentation, it's from enGene, and we have the pleasure of having Ron Cooper, the CEO, here to present for us. Take it away, Ron. Thank you. Good afternoon, everybody. It's a real pleasure to be here. First of all, thanks to the conference organizers. It's great to be back in Canada. enGene is a company formed in Canada. Our headquarters is in Montreal. Our labs are there. We have our corporate offices in Boston. We're a Nasdaq-listed company. enGene, E-G-E, I didn't forget our even our I should remember our ticker symbol, but at this very moment, it blanked me. We're listed in Nasdaq. Actually, for me, I'm also Canadian, too, so I'm very happy to be back in Canada and Toronto to see all of you today. You know, what is enGene? enGene is a genetic medicines company, a clinical stage company. You know, and I want to talk a little differently today about our company, because when you're thinking about investments in stocks and biotech, you know, as you know, there are always risks in any stock, right, that you invest in. Particularly in biotech, there are particular things that make it more risky than other sectors. I would say in the balance of risk and potential benefit, that enGene is particularly interesting, because what kills biotechs? What kills biotechs? Lack of regulatory clarity kills biotechs, inability to manufacture, clinical and commercial viability, right? I am going to talk about those through my presentation today. At the end, I think hopefully you might agree that in the risk-benefit of a particular biotech, the enGene proposition is quite interesting. As you'd expect, being a public company, I'm going to make some forward-looking statements. We have this poll right in the middle here, so I'm going to move back and forth a little bit because it's a bit odd, right? Let me start by summarizing the opportunity at enGene. It starts with our lead asset, detalimogene voraplasmid, which we're developing for non-muscle invasive bladder cancer, which I'll talk about more so through today's presentation. There are three things that get us pretty excited. The first thing is that this market, NMIBC, is going to take on a fundamental shift. Right now, it is a market with very few agents and with poor prognosis for a lot of patients. With the proliferation of new agents, we see this market moving a little bit like the multiple myeloma market. You might recall when Revlimid was launched in multiple myeloma, it was about a billion-dollar market. With the advent of another dozen agents or so, it's become a $20 billion market, a $20+ billion market. We're going to get it's going to become a prevalent-based market, so a big growing market. The second thing that's exciting is that relative to other companies, enGene and detalimogene is highly developed. We're kind of in a sweet spot right now. Why are we in a sweet spot? This year, we will finish enrollment in our pivotal study. We'll give you a data peek later this year. Next year, we anticipate top-line data and a filing of our BLA. We're hopeful of an approval and launch in 2027. We're kind of in sort of the money period of the organization. The third thing is our product, detalimogene voraplasmid, detalimogene. Detalimogene is a unique product. It is a genetic medicine. It's a lyophilized powder. We've already demonstrated good efficacy, excellent tolerability, and an ease of handling that none of the other agents have in the market and the projected agents will have. We're a real advantage. The other thing that causes biotech companies to implode is a lack of cash. At enGene, we feel pretty good about our cash position, just a little bit below $275 million. We have cash into 2027. When you look at some of those inflection points, it's beyond those inflection points. That gives you the big picture of the company. Let me move on to first NMIBC. What is NMIBC? Non-muscle invasive bladder cancer. Bladder cancer breaks into two parts: non-muscle invasive, which is sort of a slower disease, or muscle invasive metastatic, which is really serious, right? They are both serious, but the time course is different. The majority of the patients are in NMIBC. You see here about 730,000 individuals in the U.S. On the left of this cartoon, you see the various severities of this disease. On the far right, T1 disease is the toughest because it is starting to get closer to the muscle, right? On the far left is CIS, carcinoma in situ. That is a serious disease, too. The problem with that is it is like a plaque. It is like a hard plaque that goes all around the bladder. That plaque cannot be cut out, and that poses real challenges for the urology community. That is really tough to deal with. Now, when you think of bladder cancer, you think, how big is the bladder cancer market? Folks always think about, you know, lung is big, breast is big, or the like. Bladder cancer is the top 10 cancer. It is a cancer that is pretty costly to the healthcare system. The unmet medical need is definitely there. How is it managed? When you think of cancer, you think it's oncology. The first thing I want to dispel with you, bladder cancer is generally managed by urologists. It's not oncology, even though it is cancer. The second thing is you say, you know, it's urologists, but is it academic or is it the community-based urologists? Mostly community-based. The choice drivers and the needs for those community-based urologists is different. 70%-80% of the patients present to community urologists. The other thing to note about NMIBC compared to, say, stage four lung cancer or the like, it has a 20% chance of progressing over a 10-year time frame. It is a different disease to be managed. Just to summarize, managed in the community by community urologists. It is a very serious disease, but you have time. Now, when you think about the treatment of NMIBC, it is usually BCG, right, which is in short supply in the U.S., or you land up with a radical cystectomy, which is effectively removal of your bladder. That, you know, it is as bad as it looks in this particular picture, right, because it is a long surgery, six-eight hours, has up to 10% chance of mortality, but the morbidity is probably just as bad. You land up with an ostomy bag. The prostate is removed, so you usually lose sexual function. The morbidity is absolutely horrific as well. Then you think about, well, what about the medical treatments? As I've indicated to you before, BCG, at least in the United States, has been backordered for almost a decade. It's an effective agent, but it's hard to get. That's the first-line therapy. Because there's a shortage of BCG, individuals have been using different forms of chemotherapy, which they administer intravascularly. Those have had mixed results, both from an AE perspective and from an efficacy perspective. There have been three new agents that have been approved for the management of NMIBC. These three agents, though, while they have some attractive qualities and they do have a place, they're just not ideal agents for the management of the disease. You think of Keytruda, which is a wonderful drug that has saved so many individuals around the world and so many diseases. In NMIBC, unfortunately, if you look at the efficacy rate and the adverse event rate, they are very comparable almost, right? The adverse events are very difficult for urologists to manage for a disease that is sort of a slow-burn disease, 20% progression. There is a product called Adstiladrin, which is a viral gene therapy, which has, again, some challenges because it is a virus, requires thawing. There are some challenges that go with that. There is a product called Anktiva, which is a combination product with BCG. It needs BCG to really work effectively. You are in a world where BCG is short. If what I've described to you is an area of high unmet medical need, NMIBC, that is a disease that progresses to 20%, that the real treatment right now is removal of someone's bladder, when you look at some of the pharmacological medicines, while they have a place, they have some limitations. That's why we're pretty excited about detalimogene, because what has detalimogene demonstrated thus far? Demonstrated really interesting efficacy, 71% complete response rate at any time, really interesting tolerability. Our AE rate in some data that I'll share with you shortly, the AEs are grade two or below. Most patients say they don't really notice the product. It's almost, you know, saline-like, right? Very little that's administered, 50 mL at a time. From an ease-of-use perspective, because it's not a virus, it's not a device, it's actually a product that can be sitting in the doctor's freezer, refrigerator. It can be handled. There's no special handling or the like. It's just very easy to use and slips into the practice quite easily. You know, why one of the reasons these companies, these biotech companies fall apart? Manufacturing, right? And there's been some history in this category and manufacturing challenges. I've talked to you about the BCG shortage, etc, etc. The nice thing about what we are doing at enGene, we're already manufacturing at scale. Our manufacturing process is already well characterized. We actually believe this will be a commercial advantage of ours. We'd likely have, you know, the lowest cost of goods to work with in the marketplace. That is why we think that detalimogene voraplasmid has the potential to really be the cornerstone therapy for the treatment of NMIBC. What is detalimogene voraplasmid? This is where our Canadian-developed platform really begins to shine. Because when you think of gene therapy, what is the problem with gene therapies that we have? Toxicities, the amount of genetic material, so the package size and manufacturing challenges, right, are but three of the many sort of challenges with a therapeutic area that is so interesting, can be so good for patients, right? What we do is our drug product fits into what is called a DDX nanoparticle. I will show you what the components are. Effectively, what we have is technology that takes that plasmid. We administer intravesically. You see that on the far right. We bathe the bladder. We're able to get across the bladder lumen and to deliver a really interesting genetic material, three actual large genes, two RIG-I and one IL-12. I think many of you are familiar with some of these genetic materials, particularly IL-12, known to be a pretty effective anti-cancer product, but unfortunately, high level of toxicity. That together gives us a really one-two punch that's really interesting. We're able to impact both the innate and adaptive immunity with that. Now, getting back to what I said before, how about making this detalimogene? What's beautiful here is that detalimogene is made of four ingredients. These four ingredients are readily available on the marketplace. We don't have any special sort of solvents or air, you know, air that we have to use, purified, anything like that. Just really straightforward. What we do is we create a plasmid DNA. The secret sauce is the proprietary sugar polymer, the DDX, which was, as I said, that's our platform that was developed here in Canada. Together, we mix those together. That forms the nanoparticle. We dump in some PEG, right, some PEG in bulk mixing. Then we line up with our non-viral drug product. Literally, it's a lyophilized cake, right? So easy to handle. You just put water in it, syringe it out, and then administer it to the patients. As I said, already manufacturing at scale. There's no special handling or anything fancy like that. Now, what does our program look like for our development program of detalimogene? Our pivotal program is underneath what we call the Legend program. The pivotal cohort is a cohort of about 100 patients, which are patients who are BCG unresponsive NMIBC patients with cysts, right? They've had BCG. They haven't responded. They've got those plaques. We're looking for about 100 patients or so there. We also have three other cohorts. One is for patients who have never been exposed to BCG, one who've had exposure to BCG, and one who doesn't have cysts but has papillary only. That's the little growth. We're not a one-trick pony. This is a beautiful platform where we have potential to actually deliver genetic material to any mucosal area. Our team is actually working on, you know, multiple other applications for dental imaging or multiple applications for the platform as well. The other nice thing about it, what's another thing that blows up these biotech companies is lack of patent protection. Because we have invented this particular platform, we have IP into 2040 and hopefully beyond. That is where we are from a development perspective. Let me go a little bit more detailed into the Legend program and the pivotal program itself. As I said before, it is BCG patients who are unresponsive that have cysts. This is a global study where we have sites in the U.S., here in Canada, in Europe, and in Asia-Pacific. The dosing for detalimogene is the patient comes in week one and two, week five and six, rinse repeat three times a year. After you make it a year, you just come for week one and two. This is a lot less than some of the other agents, including BCG, which is six weeks in a row. That is a big difference. Our endpoint is a complete response rate at 12 months. I'm going to show you some data that we shared last fall, which we thought we were pretty excited about. It's the first time that we had shared data at a consistent dosage and a consistent dose. The first thing to note here, I'll just give you a couple of things to note in the baseline characteristics. The first thing is that NMIBC is predominantly a male disease, and the average age is usually in their mid-70s. We're pretty close in that perspective. The other thing I'll have you note on this chart, go down to the third last column, and you see there are 14% of these patients that are T1 patients. You might recall from my earlier comments that T1 patients are those that are the most severe, right? We had a disproportionately high number of that, and I'll come back to that in a second. First thing, remember what I said about tolerability? Here is the total database of all the patients in the phase II program. You can see here that anything above grade three, four, five, there are all zeros in that. It's all grade two or less. Nobody's dropped out of the study. Most of the adverse events are related to the catheterization. Really well tolerated. As I said, when we talk to the investigators, patients say, you know, it's almost like they get saline. They don't really, really notice it. Now, how does that tolerability compare with some of the other available agents and some of the agents in development? If I take you to the third line down, we had 48% treatment-related AEs of any grade. You see how that compares against the CG product, the J&J product, and the three products that are on the market. I would just draw your attention to the last column, which talks about grade three or above. These are now, you know, AEs where potentially you might be hospitalized and the like, where we have zero. You see that some of the agents where you have to make a risk-benefit decision in regards to using, you know, those medicines. How about efficacy? Here we were delighted to show, and I shared with you earlier, a 71% complete response rate at any time, three-month response rate at 67% and 47% at six months. In Kaplan Mark, if you'd project the ones that went to three, we're at three months. That would get you to 51%. We have an active compound, an active compound with really good efficacy. I will say we believe that with this data peak, that this is probably for us that we've the low bar for efficacy. We believe we've left some potential efficacy on the table. Why is that? Our protocol previously was very oncology-focused, and it did not really reflect the AUA guidelines for management of patients with NMIBC. We have made a number of protocol changes, and we think they're going to have a material impact. The first one being, remember that T1 thing that I pointed out to you? The other companies, most the percentage of T1s in their studies is usually in the low single digits. Ours is in double digits. One of the things that we were doing is with the T1, you see that was a growth. We were allowing folks just to cut it out and then put people into the study. Now we asked them to cut it out twice, so two TURBTs. If there's still T1, they do not go into the study. If there is, if there's no T1, it's known that that second TURBT actually is therapeutic. The patients that go into the study then should have a response. You know, those that, you know, were more problematic will probably not go into the study. The net is we should have fewer T1 patients going forward, and those that are in the study should have a higher chance of responding. The second thing is you'll note in that previous slide, at three months, the number of patients dropped out. Some of those patients had what are called TA disease, so a growth. Our doctor said, you know, we just want to cut that out and keep them on therapy. We didn't allow them to do that. In fact, standard practice is to cut out that TA lesion and keep them on therapy. We think that's going to have a material difference. The third thing is that we allowed people to come out of the study if the doctor looked into the bladder and said, oh, it looks like it's progressing. That adds a bit of subjectivity. Now we ask for a biopsy to confirm whether there is progression or not. We believe these three changes, which are consistent with AUA guidelines, actually will help us with our efficacy and that we've actually artificially handicapped ourselves for those first 20 patients. The next 80-odd patients will benefit from these changes. Now, how does our efficacy compare to some of the agents that are on the market and those in development? I think it's pretty competitive. If you look at a CR rate at any time, 71%. You know, if you look down to the second column, second row down, very competitive. Our CR rate at six months at 47%. The comparator, the best comparator for that is the CG Bond 2 study, where 47 and 44 were kind of similar study designs. What you see there that the good folks at CG actually made some protocol refinements, and that actually helped boost their six-month CR rate. We are making protocol refinements as well, which I talked about earlier, and that's why we expect our rates to go up. You can see here, very competitive rates. Now, you look at the bottom line. The bottom line is, you know, the CR rate at 12 months. And that's what you get approval from. Based on what we've demonstrated thus far, we feel pretty good about our chances of approval. Because if you look at the FDA guidance, they issued draft guidance in 2018. They reiterated that guidance last summer. You see three drugs have been approved, and the monotherapy products, 19%-24%. Getting back to what I said before about risk, regulatory risk relatively low. Clinical risks, we can see that we have, you know, an active compound relatively low as well. What do we land up with a product with detalimogene voraplasmid? Here's the profile that we have, which I think is a marvelous profile, right? We have a product that's actually quite practical and differentiated, right? It looks like we have clinical activity, right? So it looks like it's actually doing something kind of special. Patients seem to tolerate it very well. As we talk about the handling of these busy urological practices, particularly these community practices, the barrier to usage is lower. Now let's look at it from the lens from the doctor and then look at it from the lens from the patient. What does the doctor experience with detalimogene voraplasmid relative to the other compounds? You get efficacy, right? You get good tolerated, and you know, they don't have to change their practice. In the event that they use the BCG product, right? In that case then, you know, their offices likely will need a - 80 fridge. This is an active virus. It's a non-attenuated virus. They probably need a hood. They need a nurse that will administer this. They're going to need to do some decontamination. In their study flow, because the patients need pre-washes, there's four pre-washes right now, it just takes up more time in their offices. The J&J product TAR-200, you know, that's a product where you use a device to deliver gemcitabine. Patients have to come in every three weeks. They need a procedure room. They need people to help them with the procedure. I talked earlier about the trade-off, having to have that discussion about AEs every three weeks. That's TAR-200. It's a product that's on the market. Again, you know, this is a virus. It has some handling. You have to handle it carefully. It takes a while to thaw as well. In terms of their impact of their practice, these other agents take a significant amount of time. If you then look at it from a patient perspective, right? If you came into my office and I said to you, your BCG is not working, you have NMIBC, bad news. I would say, look, do you have an hour? Because our medicine is right there. It's right off the shelf. There's nothing, there's no pretreatments for detalimogene at all. When you're done, because it's not a virus, you can just go home. There's no need for bleaching urine and the like. Whereas for the CG product, you know, it is a virus, right? That means that there's care that's needed. It is a product that requires four pre-washes. There is detergent and dwelling. And then, you know, afterwards, you know, the return to home is different than what would happen for dental imaging. Similarly, for TAR-200, it is a piece of plastic. It is a foreign body. There is a sensation of when you void that you have that piece of plastic there. We talked about the AE profile. And then third, Adstiladrin, as I said before, you know, these are patients that often have to spend, you know, a good part of the day in the clinic. That being, you know, oops, wrong direction. You know, that being said, we are actually quite excited about all these complementary agents because we believe that physicians will be sequencing these products. Given that the data suggests most of these agents have a recurrence rate, you know, sorry, a CR rate of 20%-40%, that means a recurrence rate of 60%-80% in one year. Patients will go from medicine to medicine to medicine to help them avoid muscle invasive bladder cancer or avoid removal of their bladder. These are all complementary therapies. That being said, with the profile of detalimogene, we really believe that could be the cornerstone of therapy. We also have a terrific team. You see here, these are individuals that have a lot of experience in biotech or in big pharma, have brought drugs, you know, to the marketplace. Let me close by again talking about sort of, you know, risk within biotech, right? What causes these companies to implode, right? If you look at enGene and detalimogene, in the balance of risk-benefit, you can see here there are some really nice advantages, right? The first being, you know, hopefully what you see is clarity in the regulatory path. What you see here is that we already have clinical data. We can manufacture and we have good patents. From a commercial perspective, this is a market that's going to grow. Yeah. With that, I will again thank the conference organizers and say, really appreciate you all being here. Thank you.