Conference Transcript - ENGN 2026-09-08

Yanen Zhu, Analyst — Wells Fargo

Great. Thanks, everyone, for being here. My name is Yanen Zhu, and I'm one of the biotech analysts here at Wells Fargo. It is my great pleasure to be joined by Ron Cooper, CEO of NGIN, here to talk about the company's updates. Thank you, Ron, for being with us.

Ronald H.W. Cooper, CEO

Well, real pleasure to be here. Appreciate the invitation.

Yanen Zhu, Analyst — Wells Fargo

Great, great. I was wondering if you could start us off by giving a quick overview of the company, the initiatives.

Ronald H.W. Cooper, CEO

Yeah, sure. So, you know, NGene is a public company. We are focused on non-viral gene therapies. So very unique platform that we have. It's a company that's well advanced. Our lead asset, deadly limogene voroplasmide, 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're 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 an exception approval next year. This morning, we announced our quarterly. We have $266 million of cash, and that gets us through all of those things. So we're a company that's well capitalized, and that's poised for a real growth period.

Yanen Zhu, Analyst — Wells Fargo

So let's focus on Legend. You released interim data in May. and of course as you said you will have another readout I think that's 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.

Ronald H.W. Cooper, CEO

Yeah sure you know so we're a public company we're also a Canadian company our disclosure requirements are different the study the legend core one study is an open label study and we provided a data update in May which from our perspective of the market grossly overreacted to and I will tell you why so first off when you think about these products the primary endpoint is complete response rate at any time we we displayed a 54% CR anytime 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? And if you look at the products that are approved, that is a pretty tight range, about 40 to 50%, so let's call it half of the patients. We had 21 patients that were complete responders that had not progressed to that point so it's a little bit early for for us another endpoint that is it's a Wall Street focus is 12 month CR landmark number and at that time you know we had again immature data but projected to have around you know 25 percent so that's the efficacy part of it that's always just half of the story right the tolerability part of our medicine is really important 80 percent of the patients are in community practices and community doctors really make want to have products that are efficacious and tolerable easy to use and our tolerability continues to hold even with more more exposures for example you know our treatment interruption and discontinuation is very low 2.4% or many other products are in double digits or high double digits so I think you know We shared what I consider to be a pretty solid data update where our CRN, the primary endpoint, is in line with other products. Tolerability in line with other products, but probably best in class from that perspective. And an immature durability data set, which we'll hear more about in the fourth quarter of this year.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it. So for the fourth quarter data, It 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?

Ronald H.W. Cooper, CEO

Well, I think there are a couple things that we're looking for in the fourth quarter. So, first of all, CR any 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'll have some more data on that but probably not all of that data the 12-month landmark number we will have the majority of though of those patients but we will have that information and then hopefully around that time as well we would have had an opportunity to meet with the FDA and we'll have some insight from our pre-BLA meeting.

Yanen Zhu, Analyst — Wells Fargo

Got it. So, you know, I think you alluded to this earlier. How do you see data limo gene positioned in the high-risk non-muscle invasive bladder cancer space, and 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 do you think you have an edge and can fit?

Ronald H.W. Cooper, CEO

Yeah, our market research suggests that dental imaging will have a very strong position within the NMI BCE high-risk space. Why is that? First of all, when you look at the marketplace, Let's call it, you know, 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. You know, the academics in general would prefer to go to radical cystectomy because removal of the bladder has a 100% CR rate, right? And it's easily accessible to them. But most patients don't want to have organs removed, right? And radical cystectomy for an average patient 75 years of age, you know, 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 your 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, and recently, and Lexo has given them a product that they can actually use. And so that's pretty exciting for them. Where we see dental imaging, dental imaging 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 and so we do market research with community urologists they say to us what do they want well they want efficacy we have efficacy with dental imaging they want something that is tolerable for their patients we're trending towards best and cost 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 dental imaging will be preferable compared to other products.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it, got it. I think you know you just talked about you know what community doctors want right so I think that's a very good framework so you know on ease of use and sliding into their practice this this one you have the best in class right I think you you just stated on safety is that also you know among the best would you say that that's another strong strength another strength for their limo gene on efficacy I was wondering you know you mentioned these doctors do want efficacy right so on what level and how different our community that are community doctors compared with academics when, you know, I guess both of them will want efficacy. But how are these two different and what are investors missing? Can you help us understand?

Ronald H.W. Cooper, CEO

Well, I think it's the combination of things, right? You know, 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 Dental Imaging 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. So that's the first point I would like to make. Yeah, 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? So they are in, you know, areas with not as, you know, not as much infrastructure. They're often, you know, there's, they're stretched for the number of urologists. They're under pressure from their owner's private, they want to deliver very good care, right? So what can a product like dental imaging allow them to do? It is easy for them and easy for the patient, right? So right now, our market research says that they want efficacy, tolerability, and ease of use. You know, the dental imaging journey is one of, you know, the patient comes back, and the doctor would say, sorry, your BCG isn't working. I'm going to start you with dental imaging. 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 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 on to that for an hour and just void it into the toilet right that is really easy versus there are other medicines where you know 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, you know, if it's first six weeks, it doesn't work, then another six weeks. And then there's precautions. And even for alexo, you see these precautions, right, where you need to wash clothes separately, use separate restrooms if you if you spray your leak clean up you need to bleach bleach your urine we don't have any of that right so what does this mean for the experience both for the for the for the practice and for the physician dead eliminate slides in quite easily for both okay got it got it yeah yeah so then um you know there are 20 percent uh you know i think you mentioned 20 percent of the patients are being seen at academic centers and so you know for these places I think are you saying that you know dental imaging is the main

Yanen Zhu, Analyst — Wells Fargo

area of focus is in a community doctor space right so the academic center is not necessarily something that you you want to compete in yeah what's interesting for us, like, we started to get more sophisticated in our market research.

Ronald H.W. Cooper, CEO

Like, everybody first says, well, it's 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 are, you know, that have attributes or needs that fit very well for dental imaging. So our feeling is that we will penetrate more in the community and even in some subsets of the community. For academics, I think, you know, the dental imaging profile is more of one that fits in as being something different, right? Because what they tend to do is if a patient doesn't want radical susectomy, you know, they will give them an immunotherapy, then a chemo, an immuno and a chemo, we would be the only non-viral gene therapy. And so 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's a unique non-viral gene therapy.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it. And for the academic center, I think these are the doctors who really care about 12-month CR rate. So as you were discussing, your data weren't quite as mature at the interim. For the final, do you think that 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's the case, then why is that the case? Because I think for some other companies, is the Kaplan-Meier curve estimate may not necessarily be what they later produce.

Ronald H.W. Cooper, CEO

Yeah, so I think, first of all, when you start looking at these agents, it's exciting for doctors to have new agents, right? I think we're getting a little bit too caught up, though, in the reality is these studies are tiny, right? We have the largest at 125. Some are as small as 70. So if you really put them on top of each other, They're probably the air bars who are on top of each other, right? So when we get into real life, you know, I'm not so sure. A lot of this will start to wash out. And in real life, it will be really about, you know, does the patient tolerate it? What happens to an individual patient in individual practice? As it relates to durability, you know, in our April update, you know, the Kaplan-Meier curve said we'd 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 don't know how long they are going to progress. So the Kaplan-Meier is overweighted by those non-CRs. That's the majority of the data. So I think, you know, we feel, we have to see how the data progresses, but we feel pretty confident that we'll be in the Kaplan-Meier range. And that would be similar to other products that have been approved.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it. You know, in terms of the framing that, you know, these are small studies, error bars largely overlap, I guess that also applies to, like, anytime CR, whether it's, I don't know if, would you consider 54-55% different from 74-75%, for example?

Ronald H.W. Cooper, CEO

I don't in real life, right? that's the nice thing about our so what folks are you know forget that that's the primary endpoint that's the one the FDA would look at we're right in the range of others right I actually see very little differences in these small databases I think what's 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 dental imaging 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 that on the risk part of it is the progression, you know, progression is 3%, very low, right? And it's a little bit of progression, right? So the risk benefit for a doctor to use a product like dental imaging early is very low. Well tolerated, easier on the patients. You're going to know very quickly if it works. If it doesn't work, you're not going to do very much in the way of harm.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it. Let's talk about regulatory paths and filing. so you know have you had had any recent interaction with FDA especially on the point of what patient population or subgroup to include for the pivotal data set yeah so we we have a lot of interactions with the FDA and you know in terms of statistical analysis plan that's a back-and-forth process right That will take a while to finalize.

Ronald H.W. Cooper, CEO

So we have not finalized that as yet with them, but we do know of the 125 patients that we've reported, our final number will be a subset of that.

Yanen Zhu, Analyst — Wells Fargo

And given that you're planning to submit BLA second half of the year, is there a pre-BLA meeting scheduled? and, you know, and also just in general, what has been the area of focus in your interaction?

Ronald H.W. Cooper, CEO

Yeah, so we announced this morning that we're on track for pre-BLA meeting in the fourth quarter of this year, so we're pretty excited about that. You know, and I think when you think about, you know, the modules that go in, just to give you a perspective of things, the manufacturing module is probably five to eight times the size of the clinical module. So in fact, having RMAT designation and CDRP allow us to have a lot more dialogue with the FDA. And the nice thing about our product from a manufacturing perspective is we've 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. And so that's probably the biggest focus of our dialogue with the FDA to make sure that we're on track from a manufacturing perspective. And I think you know that most CRLs of late have been for manufacturing, not for clinical. And particularly in this category, that's been an issue. That's 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've had a really robust dialogue with the FDA. and I think we can provide to them what we want. So I think that minimizes the risk in that space.

Yanen Zhu, Analyst — Wells Fargo

Okay, got it. And maybe looking ahead for potential commercial opportunity, I think we talk about this community offices kind of focus. I think at your investor day recently, you talked about 8,200 patients in, I guess, every year in a community setting, right? But you also further carved out 41% being, I guess, the most addressable opportunity for data limergy. Can you talk about that level of focus and help us understand what might be your penetration, your positioning in that very specific group?

Ronald H.W. Cooper, CEO

Yes, let me just correct that a little bit. So if you think about it, what we believe is the incident population is around 20,000 patients per year. Some would say it's as high as 40,000, depending how you define that incident. So there's enough patients there. The numbers that you were quoting, the 41%, the 82%, 100%, that's a subset of the incident population where we believe the dental imaging profile is particularly attractive. For instance, in our segmentation, we identify a group of practices that are called resource constrained practices. And in a resource constrained practice where they don't have a minus 80 fridge, a BSL-2 hood, don't want to purchase a bunch of PPQ, PPE to administer the product, or don't have a nurse that will handle a virus, right? That type of practice is really ripe for a product like dental imaging right where anyone in the you know any qualified medical individual can can administer dental imaging dental imaging will sit in a regular fridge freezer for many years probably and multiple months in in the regular fridge so again I think we define the market opportunity overall about 20 to 40 depending on the definition 41% of that we think are really super super targets for for dental imaging itself so it's a 41% of the 20,000 not of the 80,000 yes yes roughly about that after the 8,000

Yanen Zhu, Analyst — Wells Fargo

right yeah okay okay thank you for clarifying that can we also touch on re-induction I think you touched on on it when you talk about the competitive landscape, some other therapies require re-induction. How do you think about re-induction? I think the rate of response in the LEGEND trial is, you know, like 14%. In light of that, in the commercial setting, do you anticipate there will be re-induction use or, you know, essentially there shouldn't be re-induction use?

Ronald H.W. Cooper, CEO

Yeah. Unfortunately, that word re-induction is used a little too loosely right so for other agents where you get the medicine six weeks in a row if it doesn't work then you get another six weeks in a row that's a very intense therapy for the average age patient 75 years old right the way to think about dental imaging is we actually re-induced through the whole year right so you think about it is because we get it in week you give dental imaging 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's a very different approach. And that's deliberately designed for community urologists and patients in the community. Rather than, you know, as it is, these patients are frail patients. They've gone through a tough course of BCG, depending on how it's administered, right? The idea being is that then you go to dental imaging, week one or two, you take a break, week five or six, then you take a break, and you spread it out over time. So we do anticipate that, you know, doctors will go through that, you know, that phase of, you know, induction, re-induction before they get into the maintenance phase I see I see I see so patient who are not responding by the first you know after the first three months of treatment yeah they just go on to to receive additional therapy yeah they would get they would get the three month treatment and the six month treatment and I think there's a big difference in real life versus first the clinical trial for us at the six month time frame if there's a lesion that you know a growth of some sort the patient comes out of the trial more likely than not in real life that legion will get resected and they'll just continue on therapy for the patient right so again you got to be careful of these small trials heterogeneous patient population heterogeneous protocols versus real life I think in real life you'll see dental imaging usage be a lot different.

Yanen Zhu, Analyst — Wells Fargo

Okay. Got it, got it, got it. And maybe just in terms of lines of therapy, right, so how many cycles, you know, do you anticipate patients to go through bladder sparing treatments, right?

Ronald H.W. Cooper, CEO

And I think I hear you, if I interpret this correctly, in a community setting, dental imaging probably earlier in the line in academic setting maybe late maybe later in the line do you view like the different lines of opportunity as roughly the same or it greatly diminishes as you go up line after line so to answer your first question our market research suggests patients will get three to four lines of therapy and well 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 gonna see a boom of sequencing and a boom in in the in the prevalent population if you then if you then you know you 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 you know about a quarter of the patients have prior therapy before other than BCG and we are still showing overall pretty good half of efficacy numbers so given that these patients don't progress very progress very slowly but they reoccur relatively relatively frequently all the agents have about a 40 to 50% reoccurrence rate at 12 months we're going to need new medicines got it got it let's talk about the surfactant

Yanen Zhu, Analyst — Wells Fargo

cohort so you know obviously you you started this effort recently yeah can you talk about the you know the why you're you know adding a step right you know you have talked about convenience and that for a while but this is the extra step. So, you know, help us understand that.

Ronald H.W. Cooper, CEO

Yeah. So, the design principle for dental imaging, design 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. And 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 Dettolibagene, without a surfactant bladder rinse, we actually get pretty good transfection. But if we add the surfactant bladder rinse, we get both greater depth and breath. IL-12 expression increases around 10 times. So we're pretty excited about that. We wanted to select the right bladder rinse, though. We selected polydokinol, which is a readily available product, lots of safety behind it. But then we also wanted to see if we could find a way to make this more convenient to patients. So 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. So it'll help with the flow of patients, but also remember, you know, these are average age 70, 75-year-old patients. Incontinence is already an issue. The ability to hold it in is a difficulty. So reducing that's going to be a big patient benefit. The trade-off is it's a short five-minute installation of the surfactant. So the patient gets catheterized, five minutes of the surfactant, removal of it, then you add dental imaging, and then you tell the patients to hold it in for half an hour. So overall it's a net savings of 25 minutes for the patient. So we think at the end more efficacy hopefully and durability we'll see how the data 20 you know 25 minutes saved for the patients in the practice that's a net win great 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 one so it's BCG unresponsive patients high-risk patients with with cysts. Because polydocanol, 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 polydocanol, it looks very well tolerated, very little to none systemic exposure. However, like a proper company, you 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 right so uh that's really great news for patients and for the trial itself so now it's a matter of now starting to recruit patients and uh you know and generating the data of dental imaging plus the surfactant that will sit beside the dental imaging on its own data will this then become a s uh bla situation or Or will you need a separate trial for this setup? Yeah, I think what we anticipate is we expect an approval for dental imaging on its own next year. And we'd like to shortly thereafter follow up with a supplementary with this data. And 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 dental imaging, we have the potential to have all of the above. best-in-class product.

Yanen Zhu, Analyst — Wells Fargo

How big is the surfactant cohort?

Ronald H.W. Cooper, CEO

We're still in dialogue with the FDA as to the size of that, so that's to be determined. But we can enroll up to 85 patients.

Yanen Zhu, Analyst — Wells Fargo

And you would expect the efficacy to be greater than the current regimen or any expectation along that line?

Ronald H.W. Cooper, CEO

Well, the preclinical data shows that you get greater expression. And in the mouse model, what we did is we took a sub-therapeutic dose of dental imaging, right? And with the sub-therapeutic dose, we had sub-therapeutic efficacy. We added polydocanol, 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 dental imaging. But as it is, dental imaging on its own has demonstrated good efficacy, great tolerability, and great ease of use.

Yanen Zhu, Analyst — Wells Fargo

Got it, got it. Great. I think with that, we're out of time. Thanks, Ron, for a very, very enlightening session.

Ronald H.W. Cooper, CEO

Enjoyed it. Thank you, Yana. Bye-bye.