Okay. Welcome back to the Citizens Life Sciences Conference on day two here in Miami. My name is Salman Turcan, and I cover precision medicines. Right now I'm hosting enGene with Ron Cooper, CEO. Thank you so much for joining us today. Real pleasure to be here. Thanks for the invitation. Yeah, thanks. Yeah, so bladder cancer. Mm-hmm. Can you just set the stage? I think that it's a very interesting opportunity at the time. Clearly, lots of eyeballs, lots of news. Mm-hmm Even this week, last couple months. Can you just set the stage? What's the need in this non-muscle invasive bladder cancer, and why is there kind of like a race right now? Well, I'm really excited for patients actually. Mm-hmm ... 'cause the options for patients who had non-muscle invasive bladder cancer, kind of an earlier form of bladder cancer, were actually pretty poor. Yeah. The options effectively were you'd get BCG, and the AUA guidelines said radical cystectomy, removal of the bladder. Right? Based on that, the FDA put out guidance that if you did, you know, a 100 patient odd study, open label, you could potentially get an approval. I think this is great for patients who- Mm-hmm Who have NMIBC. 'Cause when you think about these patients, these are generally men, you know, 75 years old, you know, and older. Usually have comorbidity. They're usually smokers. They have comorbidities. If you think about the disease itself, it progresses at 20% over a 10-year timeframe. Mm-hmm. It's cancer, but it's slow cancer. To take their bladders out seems pretty extreme to me. The proliferation of new agents that have been approved, I think, really help for patients, and we're pretty excited about our technology 'cause we really think it could be the technology for the community urologists most of the patients are. Yeah. I think you kind of mentioned your asset here, right? It has certain features that make it kind of interesting. How would it fit in that landscape, and like, what are you trying to shift, right? You said cystectomy is not good, obvious reasons. Mm-hmm. Let's just relegate that to as far away as possible, as late as possible. Is that kind of the goal? Wouldn't it be great if it became a surgery that nobody did anymore? Yeah. Radical cystectomy, you know, this is a surgery with first very high mortality and morbidity. You know, it's a major surgery, right? You're taking out multiple organs, you're cutting major things, you're putting things together. It has a mortality rate of 5%-15%, so pretty high. Mm-hmm. The morbidity is really high as well, too. The quality of life for these individuals afterwards, they have, you know, an ostomy. You know, they lose sexual function. Wouldn't it be great if that went away? If you look, you know, technology like our product, detalimogene, could really make a difference, you know, for these patients. When you look at where the patients are, right? If you see the way the market segments, you know, 17% of the patients, around 17% are in the academic centers. The vast majority are in the community. Mm-hmm. 83%, around 83%. Their needs are a lot different. Mm-hmm. We think we, with the next gen product, can make a big difference there. Great. Maybe right now, can you just tell us about the standard of care, maybe with an eye on the community setting, you know, because they are so different. Kinda what is there right now that you think you can, you know, easily displace in some fashion? What can you say about these more recent launch of this, some of these newer assets like J&J's and Adstiladrin? Like, how are they doing, and how are they doing in the community setting? I think the standard of care before it was you had bladder cancer, you know, we really wanna take your bladder out, right? Mm-hmm. They start to realize that this actually while it's cancer, it's slow progressing cancer. The standard of care is a diagnosis in the community. You get BCG, and then you may get, you know, gemcitabine, intravesical gemcitabine. Mm-hmm It's a referral to academic centers. The community urologists are referring quite a bit, actually. Yeah. In an academic center, you would get a combination of things such as Adstiladrin. Maybe you would get Keytruda and then radical cystectomy. Where we see a fundamental shift in the marketplace. Mm-hmm It's these newer products that you referred to, they've done okay. Mm-hmm. They've done okay. You know, there are sales with them, and they do make an impact on patients, but they're clunky to use. Mm-hmm. They're difficult for community urologists to use. They require special handling, right? They require long thaw times. They require complications with insurance. They tend to be relegated to the smaller part of the marketplace. Right now, when you're thinking about the community urologists, though, they have BCG, which has been in short supply, backordered for a decade. Mm-hmm. Maybe gemcitabine and the recently launched, J&J product, the gemcitabine, you know, the TAR-200, right? Mm-hmm. That's where they are right now. We think it's a tremendous opportunity to transform that. When we think about Adstiladrin, what we think is a next gen product, and there'll be a series of these next gen products that really can actually help community urologists because all the things that they need, they need efficacy, they need these patients to wanna take their medicine, and they don't wanna consume resources or change their practice flow. Adstiladrin can actually address those for them. Great. Yeah, talking about some of the data that we've seen, you had an update not too long ago. Can you just summarize, you know, I guess, the good or the high points of that data set and how that fits in or compares to some of these assets out there that are maybe already approved or like close. You know, there are several that are close to commercialization. Yeah. Last fall, you know, from our LEGEND study cohort 1, which is the pivotal cohort, we provided a data update. There we demonstrated the 6-month complete response rate of 62%. That's very. It's pretty much comparable to- Yeah All the other agents, right? It's in the same range as the others. We're an emerging efficacy profile. It seems like a competitive efficacy profile. At the same time, you know, we provided an update on tolerability, and tolerability is a really important issue for these community urologists. We have one of the lowest rates of overall AEs. Most of our adverse events are grade one or two. They're associated with the catheterization. Mm. Where you really see the impact of our product, Trent, relative to others, you see the rates of discontinuations and treatment interruptions, and these are low single digits. Mm. Whereas others are, you know, in the 40s or higher or in double digits. That tells me that when we give patients detalimogene, they actually take it on time. When they get the medicine, they actually continue to use it. That's a really good thing. Mm-hmm. We share that data as well. Nice combination of an emerging efficacy profile and a tolerability profile, which we believe will be best in class. Great. Maybe just, you know, we have the six months, you know, the next big important update for you is the 12 months. Maybe already at the six months, you said you're in the range of all the other assets. Is that like 63% seemed like it's certainly surpassed what we expected or our bar? Do you think that is kind of where you want to be at? Do you think there's room like the range like what do you think the range is of an acceptable efficacy for your product with all the attributes it has? Yeah. You know, let me answer your question a little bit in the way that we think about our disclosures. We recently updated to say that we'll be providing a data update in a spring conference, Q2. Mm-hmm. Is where we will be able to update the market and actually update. We'll provide final anytime CR rates. Mm-hmm. CR anytime is the primary endpoint. Most of our 125 patients will be past the six-month timeframe. What is the range of patients with anytime CR? It's about 50-80, in that range. Mm-hmm. That's right. It's a pretty wide range. We feel pretty comfortable. It's an experiment, so we have. Yeah to wait to see what happens. Our CR in the update we gave last year was 63%. We think that we're really, you know, in that range. The next update we'll provide is in the second half of this year. In the second half of this year, we'll be able to provide twelve-month data for every long durability, longer durability and followed by filing and then a potential approval in 2027. Now, in the longer term data, this is where people get a little bit confused, right? Mm-hmm. From an FDA perspective, you look at the secondary endpoint. It is a duration of response, so a DOR. Okay. Right? The secondary endpoint is DOR. If you look at the products that are approved, that is a range of anywhere 40%-50%, so relatively narrow. Where there are some differences is in the 12-month landmark timeframe. Mm-hmm. The 12-month landmark is roughly 20%-14%. As we sit right now, you know, at 62% at six months, very comparable to the others. We have a product that's an immunotherapy. We expect it to be durable. We feel pretty confident about, you know, having good durability. As I said, you know, this is an ongoing, you know, study, so we'll see what the results look like. Obviously we've had discussions with investors around since we're on the topic of you know what's to come and the duration on the duration. This comes up a lot and it's like what can we say about the duration right? When the 12 months data comes later in the year. Looking back you obviously had protocol modifications from before. Is there anything we can glean from that data? Because a lot of those patients have reached 12 months right? Like we got a little bit of a disclosure there but is that important or is that just a very different population that we you know we would just have to do the experiment and see what you put out in the summer. Yeah, because I think we made, you know, three major protocol, you know, changes that brought what we did into standard of care. Plus, we also changed the way that we executed the trial. Yeah. It's not. I don't believe it's a very good comparator. I do think when you think about durability, you know, what are the things that could be predictive of that? Yeah. The first thing being our preclinical model suggests good durability. Second, secondly, this is immunotherapy. In general, immunotherapies have good durability, right? In our update of the fall of last year, you know, we only had five patients who were eligible to be measured at the nine-month mark. Five of five made it, right? Mm-hmm. If you look at all of the other agents, they all have a similar sort of decay curve from the earlier timeframe, for instance, to the later ones. You would have to believe that, you know, for us to have markedly different durability, something very different is happening here. Mm-hmm. That's why I think we feel very confident that we'll have a product that's durable. Great. That sounds good. Can you walk us through the important characteristics, you've mentioned a couple already, for example, discontinuations, outside of safety and efficacy that differentiate the asset, and that will be particularly important in the community setting. Well, let's go to the community. The community doctors, you know, that's over 80% of the market, right? What are they faced with right now? They're faced with the majority of their practices becoming owned by private equity, so they're under pressure, very hard for them to get staff, right? If you look right now, most of the new products. They haven't been able to use them, right? And because it's just too difficult in their practices. We really believe that detalimogene fits their needs. What do they say that they need? They need efficacy, they need good tolerability, and they need something that slides into their practice flow. How do we differentiate versus some of the other products? Some of the other products that are on the market or will come over time, right? We do not need any special handling. First of all, our product is convenient as can be. We anticipate that it will be stable in a regular fridge for, you know, many months, in the freezer for many years, whereas some of the other products are ultra cold chain, they'll need to be drop shipped. That's a logistical challenge for practices. Many other products require special handling 'cause they're viruses, right? You need a nurse that's interested. You need to terminally decontaminate the rooms. You will need to have precautions that go with it, in terms of bleaching urine and the like. We don't have any of that. Many of the other products have multiple pre-washes. Mm-hmm. If you use pre-washes, that means you're using nursing time, instrumentation, you're cleaning rooms. We don't have any of that. Many of these products will require procedure rooms to insert and remove devices, right? Mm-hmm. We don't need a procedure room. It's a regular examination room. The Adstiladrin experience actually is one that is easier for the patient, easier for the physician. You know, frankly, if I was your urologist and I said to you, "Salman, I'm sorry, BCG is not working, you know, for you. We're gonna start you on Adstiladrin." I literally will walk out of that room and I'll bill for that visit, but I'll go do some, you know, prostate or stent work, whatever the case may be. Some of my staff will reach in the fridge, mix with water, take a catheter off the shelf, a regular, no special catheter. Mm-hmm. Will instill Adstiladrin, and then, you know, five, 10 minutes later, they're gonna tap you on the back and say, "Try and hold that in for an hour and just void it in the toilet. Come back next week. Come back week five or six." Whereas many other products will be, "You have to be here for two hours," or, you know, for all the multiple, you know, for the bladder washes, "You have to come back every week," or, "You have to come back every three weeks. We have to schedule a procedure room." So you see here, this is a lot more complexity that these community practices just are not equipped to do, and that's why they really have not adapted to these 1.0 products. We really believe a next generation product like detalimogene could really make a difference in this marketplace. Mm-hmm. Certainly, yeah, there's something about the, I guess, the number of steps and things that can go wrong, right? As you integrate that into your clinic with limited resources. Have you done a back-of-the-envelope calculation of maybe for the clinic, how many more patients you could fit in a day or a week? Also for patients, how much, you know, how much less time do you spend at a doctor's office? Well, for dental imaging, let's start with the patients, right? Mm-hmm. Now, in the clinical study, they have to be there for an hour because we collect their urine. Yeah. Right? It's not an active virus, right? So there's no reason, you know, for us, you know, other than the clinical study, to collect urine. So the patient experience for Adstiladrin is you are literally there for five minutes, five or 10 minutes, and you go home. Yeah. You know, and this is interesting, we probably should do some pharmacoeconomic work. We'll do that over time. If you look up when the other agents are gonna be there for multiple, you know, for a much longer timeframe, right? They have to be there at greater frequency. For Adstiladrin, week one or two, week five or six, rinse, repeat three more times, you know, that year. It really is a pretty significant difference in, you know, in time for the patient and for the clinic as well. Great. Now I wanna go back to the point where you mentioned that before it was almost like a race, or you could count the number of days basically before you get a cystectomy, and today that may be changing. Looking at the patients you're currently enrolling in the trial, and they may be more at academic centers, how many pre-rounds of pre-treatment did these patients have, and what does that tell you about, you know, adding more and more treatments to delay cystectomy? Yeah. I think, you know, I think right now, on average, it depends on the patients, but it's somewhere between two and three rounds that they're getting. Most of those rounds are occurring in the academic centers. Mm-hmm. Because the academic centers have staff, they have equipment, you know, they have ultra cold chain storage, they have rooms that they can use, right? That allows for those, you know, two or three, you know, lines. Right now, the community urologists are actually referring a disproportionate number of patients. They're. They have BCG, maybe chemo, you know, intravesical or gemcitabine, but that's about it. Where we see the growth occurring is multiple lines there. We believe that with these next generation products, next gen products, where detalimogene leads, there'll be next generation products that the community urologist can sequence 'cause it slides into their practice flow for them. It's great for patients, it's great for the practice 'cause they retain the patients. Plus, you know, in a buy and bill model, they generate revenue. Patients are happier because they don't have to, you know, drive into the city to go to a major center. They're closer to home. Everybody wins. Mm-hmm. Great. Have you done some research or data sets or do you have some surveys with doctors or particularly in a community setting, kind of seeing if they understand the need or if detalimogene fits what they need for their practice? Yeah. We're in the early part of market research. It's pretty compelling actually. You know, what the market research says, you know, it is efficacy is obviously important, they want efficacy, but tolerability is really important, right? 'Cause when you think about these, you know, more elderly patients, they've already had, you know, some, you know, heavy duty BCG, right? BCG is, you know, six weeks in a row, and then maybe another six weeks after that, right? As you know, with BCG, you have increased, you know, toxicity that goes with it. To go to a medicine that is really well-tolerated, as it's been seen within the LEGEND program, it's almost easier to convince a you know, elderly patient to take that, right? Mm-hmm. I think that, you know, that's what the market research. Then the market research talks about the non-clinical benefits and just the difficulty of integrating things that change their practice flow. Products that slide into their practice flow don't consume incremental resources, really make a difference there. Great. There's one more question. We had data from one of your competitors or early competitors, Protara, which I would put in the chemo bucket. There's, you know, a few assets that are kinda like the chemo side and then the IO side. When I think about the space, like, which one would I pick? Would I get chemo on my bladder or IO, right? I would probably tend towards IO. Your stocks sold off a little bit when this news came out. Like, what's your take on that? Like, it is not a direct competitor and there are no, to me, obvious outsized benefits. How do you view that? Well, I would agree with you, this is not a direct competitor. This is a product that will be complementary, but it's, you know, quite a ways away from a timeframe of when it would be approved. I agree with you. I believe that it may be one of those next gen products, right? That when a doctor goes, "Okay, now I have the opportunity after BCG to use detalimogene," and I talk about next gen products, then it you go to a chemo, they'd have the choice of gem, right, on its own, which is, you know, it's not comfortable for patients. It takes up a lot of practice time. It's not good economics. They could use the J&J product, TAR-200. That comes with some challenges 'cause, you know, it's a you know, there's. You know, it takes time to put in and out. You've got to be there every three weeks. Maybe the new product from Protara could be useful there. Mm-hmm. However, you know, I believe what they announced is that, you know, they're just starting their pivotal program, and the FDA guidance has changed a little bit, right? When we went to the FDA, when the new products were coming, it was if you fail BCG, then you get your product. Their clinical study will have BCG, any of the new products, then they'll be used. They'll be a third line product, right? Mm-hmm. You know, having just recently enrolled our study, you know, it's gonna take a little while to find those types of patients if they're just starting right now and then by the time you get their approval. I think it's a long way away. In the data that they shared, you know, not one of those patients actually fits that criteria. You've got to make a bit of a leap from the data they shared towards, you know, the data that are gonna be in their pivotal program. You know, in summary, I don't see that as a competitor. I actually see it as a complementary medicine. It's gonna be great if we have that, you know, that medicine for patients, but it's gonna be a little while before it's there. Mm-hmm. Great. Then you guided to a new update in the second quarter, where we'll get the incremental data on the six months, all patients having reached six months. Is there anything else? I mean, people will obviously look which way that six months data shifts, but is there anything else that you wanna point investors to in that data set that could be of interest? Well, I think it's pretty exciting for us to actually be finished and say that here's the primary endpoint, this is where we're gonna be, the anytime CR rate. I think that's gonna be good news. Then, you know, again, I kind of explained to you how important tolerability is for this patient population relative to other patient population. We'll give an update on that. Then we'll try and characterize as much as possible, you know, some of the long-term effects. You know, we're gonna have an incomplete data set, so we'll probably do something similar as to what we've done previously. I think all of those things I hope are of interest to our investment community. Great. Then, looking ahead, there's many other settings, right? In LEGEND, you got cohorts 2AB, B- BCG naive, exposed or various other settings. Can you just, you know, sum those up where they are maybe and maybe order them in terms of magnitude or importance to the, you know, the overall opportunity for the program? Which ones should we be watching? Yeah. We have, you know, cohort 2A is for naive patients, 2B exposed, and then we have a papillary only. These are patients, you know, without CIS. I would say all of you know, we've deprioritized those. Yeah. We've really focused 'cause we're a little bit behind on recruitment in cohort one, but then we really got at it, and you see that actually, you know, it over enrolled by 25%. We've gone back to those, because they're not as valuable if you know. Yeah If the product doesn't get approved. All of this will be, you know, supplementary information to help inform prescribing decisions, right? Yeah. Of those three cohorts, there is some precedent that papillary would go into NCCN guidelines, right? That could be particularly useful to us. Mm-hmm. Nice. Well, Ron, we're at time, but thank you so much for joining us today, and thanks for the discussion. Well, really enjoyed it. Thanks, Gene, for the invitation. Yeah. I look forward to the data. Yep. Thanks. Be good. Thank you.