...Welcome to the Morgan Stanley Global Healthcare Conference. I'm Jeff Hung, one of the biotech analysts. 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. For this session, we have enGene, with CEO Ron Cooper and CMO Raj Pruthi. Welcome.
Thank you. Real pleasure to be here.
So for those who may not be as familiar with enGene, can you provide a brief introduction?
Sure, happy to do so. What is enGene? enGene is a non-viral gene therapy company that is in a pivotal trial, so it's a clinical stage company. We have a proprietary platform called the DDX platform for Dually Derivatized Oligochitosan platform. And that is unique technology of where we've been able to create compounds, and our lead compound is a compound called detalimogene voraplasmid, formerly known as EG-70. We're pretty excited about that compound because we think it could really be the cornerstone therapy for non-muscle invasive bladder cancer. That compound is currently in a pivotal study that we're actively enrolling, so we're pretty excited about that. And plus, we have it in some other cohorts as well.
In addition to that, from our platform, you know, we're looking at some other models to perhaps pursue some other urological cancers as well. So enGene, you know, I think the thing to remember is non-viral gene therapy, so to crack the code on that, and actually a clinical stage company in a pivotal study that we're pretty excited about.
Great. Before we jump into detalimogene, I wanted to ask Ron a couple questions. You started in enGene in July. You know, first, can you just talk about what attracted you to this opportunity, and what does enGene do well?
I think there really are three things that got me excited about enGene. I think the first thing is the market itself, right? So I did not know a lot about NMIBC, but if you look at the current treatment, it's pretty grim for patients, right? It is a number of products that are really hard to access, right? So not very easy to access, or they rip out your bladder, right? That does not seem like a great treatment. The other thing that really attracted me is, I love it when the industry and the FDA partner really well. So the FDA guidance, where they said, "Look, you know, instead of double blind placebo, a single open label study should be sufficient for approval," I think that speaks to the unmet medical needs, so that bar changed.
And then the third thing within that is, I think I'm excited that there's complementary therapies, right? And, you know, to me, this is analogous to some other markets, you know, like for instance, multiple myeloma, Revlimid was launched. You know, the market was about $1 billion-ish, right? And that's become a $20 billion market with the advent of all sorts of great technologies, which is really great for patients. I see us at the forefront of that in NMIBC, right? So roughly a $2 billion marketplace, projected to be a $20 billion one. So to be at the front of something exciting like that, where we can make an impact on patients, very exciting. And to be in something that has great momentum at the beginning of something large, very exciting. So that's the first reason.
Second reason is detalimogene, to me, is a highly differentiated product. So I, in my experience, have launched dozens of products all over the world, all sorts of different products. You know, some products first in class, others probably me-toos. I look at this product here and wow, what a profile! Fantastic profile for both the physicians and for the patients. From a physician perspective, we, you know, this medicine really is consistent with their current practices. They literally can open up the fridge, take it out of the regular fridge, put a little water in it, you know, administer it to patients, one hour later, patients can be gone.
That, to me, is so patient-friendly and so physician-friendly, and when you consider that 80% of NMIBC patients are managed by community urologists who are very busy and very focused on chair time and productivity, it's just a gorgeous fit. The second thing within our clinical program, getting back to the first point, from a risk factor perspective, we're an open-label study, right? So we have good phase I data, we have a phase I study, and we feel pretty confident that we have an approvable drug here. So unlike when you're doing a double-blind placebo-controlled study, the risk is a little bit higher because you're waiting to the very end, I think we're tracking towards a product that's gonna be really important. So that's the second reason.
The third reason, you know, when I look at the company itself, way under the radar, right? Coming public through a de-SPAC, and then if you kind of peel it back, you look at the capabilities in the organization, you know, Dr. Pruthi has come in as our CMO, fantastic, really good CFO in Ryan Daws and the rest of the organization. But one aspect that when you do diligence on new companies that sometimes gets lost is the ability to make the material, right? And, you know, here we have a manufacturing process that, you know, it's a four-step process, four commonly available agents, right? We've manufactured at scale already. This has been a tripping point for other companies, right? I think we feel pretty confident in that.
So to me, it really, you know, three things, explosive market opportunity, highly differentiated product, Jeff, and then the third thing is this is a company below the radar and has a real opportunity for growth.
Now that you've been at the company for about seven weeks, any aspects of the strategy or approach that you think might need to be adjusted?
I think, you know, if you characterize the company, the company almost went from a Series B company to a public company really quickly. So I think there are really two things that need to be. One occurred as I arrived. You know, having Dr. Pruthi as our CMO, we're a urology company, having a urologist, you know, with his pedigree and his experience as our lead scientist is really important for our company, for us, to actually serve urologists, but also to make sure we execute on our programs. I think the second thing is, the reality is we're a pre-commercial company, right? It's not very far for commercialization. So I think a lot of our work now is, you know, getting ready to file the BLA, getting ready to launch the products.
For a small company that's been focused on research and platform development for a long time, that's a big shift. That's where we're focused in right now.
Great. Well, let's start with the treatment landscape. You know, multiple treatments are approved that face meaningful headwinds. You know, cretostimogene grenadenorepvec or TAR-200 could be on the market before you submit your BLA. You know, how do you see the landscape evolving, and how do you view detalimogene voraplasmid fitting into the treatment landscape?
I think it's, you have to step back a little bit and think about this disease, right? So non-muscle invasive bladder cancer, if you look over a 10-year timeframe, it's a 20% chance of progressing to muscle invasive, right? So I think the first thing we have to get our heads around is, yes, it's cancer, but it's not oncology cancer, it's not breast cancer, it's not lung cancer. You've got time, right? That's number one. The second thing is, this, while it's cancer, it's urology cancer, and it's not teaching hospital urology, it's mostly community urology, right? So that makes the choices different, right? And so that's why I'm pretty excited about these new advances. I think they're complementary therapies, and what I see occurring, much like in multiple myeloma, there'll be sequencing of these agents. And that...
There's a real incentive to do that, both from a patient perspective and from a doctor perspective. Why is that so? From a patient perspective, you know, most of these patients are in the community. So we're in New York today, but they're in, you know, Summit, New Jersey, right? They wanna stay close to home. Their local urologist is, you know, twenty minutes, twenty minutes away. If they can get multiple treatments there, that's gonna be better than having to come into the city and go to Sloan Kettering and the like. So I think these agents being delivered closer to the patient here is gonna be good for them. But it's also there's an incentive towards these urology practices because they want to avoid cystectomy, right? You know, that's, you know, cystectomy has 100% CR rates, right?
But, you know, that 10% mortality in that surgery, 68-hour surgery, high level of morbidity, it's not a great solution. So for patients' satisfaction, I think urologists would like to try different things, right? And there's also an economic aspect of it. I think urologists wanna keep those patients within their practice. So then how does that fit in to detalimogene? Well, as I said earlier, wow, what a profile, right? You know, we all have a product that is easy to transport, easy to store, easy to administer for the doctor, easy for the patients. You know, what we've seen thus far from an AE perspective, you know, really well tolerated, actually. Most of the AEs are attributed mostly to administering the product, right?
So I think that lends itself to a profile that, you know, makes it sort of a first choice, first product that folks reach to. And because we have these great manufacturing capabilities, we think that we can have a competitive cost of goods, cost-effective therapy. So when they go to reach for it, it's gonna be there as well.
You've been talking about some of the features or aspects that help to differentiate, you know, or position detalimogene, but can you just talk about the mechanism of action and how that's unique?
Yeah, maybe, Raj, you can talk to that.
Yeah. Thanks, Jeff. Some of the key aspects to the differentiation relate to its product form. As Ron mentioned, it's a non-viral, non-integrating gene therapy, where storage, administration, development is all relatively easy and avoids some of the infrastructure that may be needed with current products or in development. The advantages is it has a two-pronged kind of tactical approach. One is related to innate immunity in a RIG-I agonist. So the plasmid encodes for RIG-I, which is an intracellular receptor, to stimulate natural killer cells and to kinda tamp back the suppressor cells to allow for tumor kill. The other is IL-12, encodes for IL-12, and IL-12 is a well-established immuno-oncologic mechanism. The problem with IL-12 has been it's tough to deliver systemic doses at therapeutic levels.
The beauty of this is it allows for encoding of the local bladder urothelium to develop that IL-12 and derive efficacy with local T cell response, which has T cell response, as well as some memory.
Great. And you talked about the ease of use in the community setting with single-step administration. You know, how are you thinking about the commercial strategy, and, you know, what kind of sales footprint would you need to cover community setting?
I think we're pretty excited about the commercial potential. One of the things that attracted me to the company is I think it's something manageable for a company like ours. So I think our go-to-market strategy in the U.S., we're probably gonna need 40 - 60 sales representatives, very manageable. And when you think about it, there's about 12,000 urologists in the U.S., but not all of them are involved in NMIBC, right? So, you know, we were in a chat yesterday with a community urologist. They have 30 urologists there, but four of them manage it, right? So it'll be a nice targeted effort. Then, as we think about the rest of the world, our go-to-market strategy be, we'll assess that, right? And so I think when we think about Europe, Asia- Pac, and rest of world-...
You know, likely we'll talk to partners, but we'll also evaluate if it would make sense for us to go it alone or not. But I think, you know, this is something that's pretty manageable for a company of our size.
Now, in terms of manufacturing, you know, what remains outstanding on scale up, and, you know, what is the manufacturing capacity that you have now, and any plans to increase that, you know, post-launch?
Yeah, I think, you know, there are two things about manufacturing. We want to be able to submit the BLA, and we want to be able, on day one, when, when Dr. Pruthi's colleagues go to reach for it, it's there, right? So those are the two things we need to do. I feel that we're in very good shape for both things, right? So getting back to our manufacturing, you know, it is four steps. It's four different products. They're all readily available. We use water, right? It lyophilizes the compound, so it's all simple to handle, right? We've already manufactured at, at scale, right, you know, to be able to do our pivotal program. So, you know, we have the regular stuff that you have to do to fulfill FDA requirements, and we will do that, but we're on track for that.
So I actually feel this could be a real competitive advantage for us. And as I said, because the raw ingredients are relatively common, at the end, I think our cost of goods is gonna be, you know, very competitive, and I think we'll be able to deliver a cost-efficient product at a high volume that the community urologist can reach for, and it's gonna be there.
Now, your interim results are expected by the end of the month. You know, what should we expect to see?
Yeah, first of all, I would characterize them more as preliminary results because interim connotes a big statistical analysis. But, you know, let's think about we're in a study of a 100 patients, right? It's an open-label study. You know, what we've committed to, you know, is around 20-ish patients. That 20-ish patients represents 20% of the study population. We'll share with you six-month CR rates and the three-month CR rates. And as well, we'll obviously share with you the tolerability data. You know, I think if you compare that to our phase I data set, so we had a phase I data set, I think that was pretty promising, sort of similar-ish size data sets.
I think it should give reassurance, you know, to the folks out there that we have a compound that's active, that we have a compound that I believe a product candidate that will fulfill FDA requirements and we'll have an approvable product. So we're excited to share that preliminary data with you.
Now, should investors be thinking about the results in the context of what we've seen with cretostimogene grenadenorepvec and TAR-200, or, you know, is that the right bar, or, or does differentiation on ease of use change that bar?
I think, first of all, you know, look, in the absence of head-to-head comparisons, I get that people will be looking at individual CR rates. So I get that. The reality of it is, and then, Raj, maybe you could expand on this a little bit more, that's not exactly how the community urologists look at things, right? It's much more complicated than that. You know, it is: Is this product approved, right? Can I get it? Will I be able to get reimbursed for it? And is it going to be relatively easy for us with, you know, within our clinic? So I think we're gonna demonstrate good efficacy, but I think if you add that efficacy up with some of the other advantages, it makes it compelling.
Maybe, Raj, you can talk a little bit about, you know, when a patient comes in, what urologists are thinking about for these different agents.
Yep. Thanks, Ron. I think that conversation that happens in that clinic room, Jeff, is much more nuanced as far as the patient and the doctor and what that conversation... Often what's asked is: What are the goals of your therapy? Is it to maximize cure? Well, we have something, right? We have cystectomy, that's near 100% cure rate, but it obviously comes with a lot of adverse events to that. Is it ease of delivery? Is it traveling back and forth? Do you want to go to an academic center? Is it quality of life? So I think there are these other new aspects that go into decision-making. Well, I'll tell you what I'm excited about is I've taken care of these patients for 25 years. 15 years ago, the treatment paradigm was BCG, more BCG, cystectomy.
Now, we're talking about three, four, five, six different assets in this area. I mean, that's music to my ears to have that. I think what we'll see is likely them being sequenced, as we talked about before. I think with our ease of use, that kinda speaks to potentially being the first one that they grab off the shelf.
Great. Now, there's been some confusion among investors on which measures are most important in the end. So I guess, as you're thinking about, you know, ultimately, like, the final data that you might present, can you just talk about your views on the relative importance of CR at any time, CR at 12 months, and duration of response? Like, which matter most to the FDA?
What we can look at, what is most critical, and is what we've agreed upon with the FDA, is our primary endpoint, which is a landmark 12-month CR. So that's really what we're working towards, is that 12-month CR. There is precedent with FDA approval with that 12-month CR, with Adstiladrin and Keytruda at somewhere around 20%, so I think that's something that people can start, you know, comparing to. I think CR anytime is valuable and useful. It's a secondary endpoint to us, but still valuable nevertheless. As I alluded to, I think at the end of the day, Jeff, like, these things are important. I think the landmark numbers are important. They're clear, they're as far as what that endpoint is.
I think they are ultimately at that, you know, where real-world practice. I think that's taken in context with all of those other aspects about ease of use, travel, toxicity.
... Okay, and then another sticking point following the AUA data for cretostimogene and TAR-200 was the use of Kaplan-Meier estimates for CR at 12 months. And I'm just curious, what is enGene's view on this, and do you plan to report Kaplan-Meier estimates like CG and J&J?
We also were a little bit confused about how the data was reported. We're gonna keep it simple and straightforward as possible and stick to that 12-month CR.
Okay. Now, enGene has indicated that the phase II is registrational. Can you just talk about the guidance you received from FDA that gives you the confidence for this approach, you know, versus what others have done in, in running a phase III study?
I think there are two things, right? We've had a good dialogue with the FDA, and, you know, they've confirmed to us that this program that we have is registrational, so that's check one. But I was also encouraged that in August, the FDA issued new draft guidance, and that draft guidance has come after other products have been launched on the market. And they reaffirmed in that the draft guidance that a single open-label study would be sufficient for approval. So I think we feel pretty confident that we're on the right track with the LEGEND study, so we're looking forward to getting the final results and submitting it.
Okay. And once those initial results read out, you know, can you just talk about what happens between, you know, September and then 2Q or 3Q of 2026 when you file the BLA? You know, will we get a final readout next year? And, you know, how might that differ from what we see this month, besides the obvious of more patients?
Yeah, I think, Jeff, you know, I'm relatively new at enGene, right? And so, you know, right now we're working with our current guidance. But I think what we're going to do is we're gonna sit down with the team and kind of plot out what's gonna happen between now and BLA filing. You know, so we... You know, the other thing that we have is we have multiple cohorts of data. Of course, we have, you know, Cohort 1, which is a pivotal cohort. We'll share a bit of data, some preliminary data with you by the end of September. We're excited to share that with you. But we also have Cohort 2 A, which is BCG naive, Cohort 2B is a BCG exposed.
We're also pretty excited that we're bringing up a third cohort of papillary patients as well. I think all of these cohorts expand the treatment-available population and will actually really help urologists inform them of their treatment. What we're going to do as well is you know step back and kind of look at you know when this information will be available to us. You know, those other cohorts will start by the end of this year. You'll see a stream of information you know from us you know coming into the filing timeframe, where it's still a bit of work in progress with Pruthi.
Great. Well, it looks like we'll leave it there. Thanks so much for your time.
Jeff, thank you very much to chat about enGene and where we are with detalimogene voraplasmid. We're pretty excited about where we are as a company.
Thank you.
Thank you.
Thank you, Jeff.