BoB@JPM: Ron Cooper, enGene

On this week's episode of the Business of Biotech -- on location at the J.P. Morgan Healthcare Conference -- we're speaking with Ron Cooper, CEO and Board Member at enGene, to unpack how he scaled Albireo from a small research shop to a global commercial company, and why he’s now betting on nonviral gene therapy at enGene to help patients with non-muscle invasive bladder cancer keep their bladders. Cooper talks about the importance of keeping development, financing, and hiring in sync as biotech companies grow, his experiences surviving near-death cash deficits, the importance of investing early in CMC, and what to expect in 2026.  

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Chapters

• 0:00 Meet Ron Cooper And enGene
• 3:35 Lessons From Global Scale At BMS
• 7:45 Becoming The “Fix-It” Operator
• 12:20 Why Leave Big Pharma For Biotech
• 15:24 Albireo’s Science And Patient Need
• 19:43 Syncing Science, People, And Capital
• 24:36 Fundraising Creativity And Storycraft
• 29:20 IPO Detour And Near-Death Moments
• 34:10 How To Get Bought Without Selling
• 39:15 Build Optionality Into Commercial Plans
• 44:00 The Hard Transitions: R&D To Commercial
• 49:10 Pediatric Vouchers And Policy Gaps
• 50:20 Why enGene And Nonviral Gene Therapy
• 54:30 The Community Urologist Reality And Market Outlook

Transcript

Ben Comer: 0:03

Welcome back to the Business of Biotech, JP Morgan Healthcare Conference Edition. I'm your host, Ben Comer, Chief Editor at Life Science Leader. And today I'm speaking with Ron Cooper, CEO and board member at enGene, a clinical stage nonviral genetics medicine company with a lead gene therapy candidate that aims to delay or prevent bladder removal for people with non-muscle invasive bladder cancer. Ron is an accomplished globe-trotting pharma and biotech executive who spent nearly 30 years at Bristol Meyer Squib before joining Albireo Pharma as CEO in 2015, a company he transformed from a small discovery and research organization to a publicly traded global commercial biopharma, which was acquired by Ipsen for up to $1.2 billion in 2023. Ron is also a member of several biopharma company boards, and I'm thrilled to speak with him today about how to grow, scale, and transition life science companies from small research-driven organizations to global enterprises. Ron, uh, thank you so much for being here. I know it's a busy week. Yeah, great to meet you in person, finally. Um I just mentioned that you spent almost 30 years at BMS in increasingly senior roles uh in Canada, in the U.S., across a bunch of European countries, uh including the Netherlands, the UK, and France. Your BMS's European president uh prior to your departure in 2014. What are some of the uh lessons that that you learned working across different geographies uh and cultures for one of the largest biopharma companies?

Ron Cooper: 1:49

Well, I was really blessed to have really a full career at Bristol Meyer Squibb. You know, I would call that my scale experience, right? When you work in in a company where you manage billions of dollars and you and you manage billions of dollars of expenses and thousands of individuals, you really learn about scale. So my in my experience with BMS, as you said, you know, I worked across five different countries, probably close to 20 different therapeutic areas over over the years, launched dozens and dozens of products, right? And I think you know, the theme that kind of goes through all of these things that in working with these different countries, different therapeutic areas, uh, and the like, if you continue to focus on the patient, right, and the benefit that we are trying to bring to patients, and then you then think about the team and the effectiveness of the team, and recognizing particularly that in different countries and cultures that that individuals have deep insights into their local businesses. You treat those individuals like adults, you put those things together, you land up uh with magic. And I think in my time at Bristol Meyer Squib, we had opportunities where we delivered a tremendous amount of uh top-line growth, uh tremendous amount of efficiency and earnings per share, but at the same time made an impact on a lot of patients around the world.

Ben Comer: 3:23

Yeah. And were you kind of the scaling guy? I mean, when you BMS must have identified a, you know, a talent in you that led them to move you around to so many different locations. Was it your ability to scale and grow the businesses in those countries? Was it your ability to, you know, work in different cultures and and you know, get the best out of uh uh your your colleagues in those areas? What what was it, do you think? I don't know.

Ron Cooper: 3:51

You'd have to, you'd probably have to ask some of the senior folks, but uh if I was to hasten the guest, I would say I was the fix-it guy. Okay. You know, and and and because you know, because I you know I'm multicultural, I'm globally oriented therapeutics, you know, I could come into businesses and and help assess the team and fix it, right? So I moved fairly frequently because of that. You know, I'll give you an example. You know, we we had a terrific neuroscience business, really a great business. Uh, but this was a time, you know, after we had a consent degree, we had a number of issues. The product that we had launched was A bilify for schizophrenia. It was successful in partnership with Otsuka. And uh, but then at the time we were launching in the bipolar disease area, sales were a bit flat, right? And we're trying to look for growth. And we made the organization made some changes and asked me to take on that neuroscience business. And I'm not sure I did anything really terrifically magic, right? But at the end of the day, we sat down with the team and did a really good diagnosis of what we needed to do. Part of it was we were just not telling the story correctly, right? Which um which didn't have the same impact that it needed to. So, you know, getting the team together, you know, we said, okay, let's get our strategy and story correct. So that was the first thing we did. The second thing is then we need to get the right people to execute it. So we made appropriate changes to bring in people that were really committed to delivering that story and building a culture across the organization. And then the third thing is we were blessed along the way with some really terrific data and major depressive disorders. And at the time, the company wasn't really sure if this type of product, you know, a heavy schizophrenia product would be good in major depressive disorders. But we had three studies that showed it would it was impressive. So we put together kind of a really great rationale for the company to invest in that. And um and we launched an an MDD, big market. We thought even if we get a small slice of that would be a big opportunity. And you know, it you know, now in revisionist history, we look back at Abilify, it was a pretty good schizophrenia drug. It was an even better bi polar drug, but it was a phenomenal MDD drug, right? So that was but one small example of multiple examples of where I've even gone to countries or therapeutic areas and worked the team to have you know an impact on the business.

Ben Comer: 6:20

You left in 2014, I believe. Is that right? Uh, what can you say about the the reasons for you know, after nearly 30 years um taking off?

Ron Cooper: 6:30

Well, I think you know, like anything great in life, I'm so grateful to Bristol Meyer Squibb. You know, it was, you know, we I learned a lot. I had a lot of professional growth, our family, and a lot of personal growth as we moved from from country to country. And and whether it's Bristol Meyers Squib or any other any other company, as you become more senior in organizations, sometimes you get farther away from the things that you love the most. So, what do I love the most? I love being close to the science, I love being close uh to the team, and I love being close to the key opinion leaders and patients. And I did have experiences like that when I ran our HIV virology business. It was a very tight unit, but I I found I was I was spending less time with that and more time uh with you know other corporate types of types of things. And so the opportunity seems to you know, you know, retire from Bristol Myers Squib, perhaps try something new. Yeah. Right. And that was pretty exhilarating for me. And so I took the opportunity to retire and explore life a little bit and catch up a little bit on life and and think about what chapter number two would be like.

Ben Comer: 7:44

Chapter number two uh was um Albireo. Uh you joined as uh the leader of that company in 2015. It was a small um privately held discovery and early research group at the time when you left. It was a global commercial pharmaceutical organization. Um I mentioned it was purchased for upwards of a billion dollars, over a billion dollars. Um, let let's let's take that step by step if we could. Um, first of all, uh what brought you to Albireo?

Ron Cooper: 8:17

Well, it was kind of the same things what I talked about before. I wanted to get closer to the science, I wanted to build something, and I wanted to have an in in an interaction, impact with key opinion leaders and patients, right? And when I saw Albireo, Albireo was an AstraZeneca spin-out based in uh in Gothenburg, Sweden. You know, it had some swings and roundabouts over time, but the fundamental science was really attractive, right? Very simple science. Effectively, it said bile acids in the wrong place are bad. We have a technology that can take bile acids out of the body. Very elegant small molecule uh approach. When I arrived, we had some early data in a rare pediatric uh disease setting. And boy, oh boy, you know, I don't know, you know, if you know people in the audience or yourself, you have children, but you know, there's nothing worse than seeing children suffer. Yeah. And absolutely these diseases were diseases where you know, these poor young parents have young babies and the babies are like scratching themselves, almost peeling off their skin. You know, the babies don't sleep, the parents don't sleep, you know. It it's just horrible, right? And the only choices they had really for treatment was removal of their liver per se, or you know, uh disfiguring surgery. So that to me was pretty was pretty attractive. So science was attractive, the impact on patients, and frankly, it was just off the radar, right? And off off the radar, I thought, well, we could take this thing, you know, prime time. And so when the board looked at their science and said, we have something here, but we need to kind of accelerate this, you know, I became employee number one in the US. So it was effectively myself and you know, a dozen Swedes, and we got up and going.

Ben Comer: 10:11

Yeah, okay. And then what does it take? I guess for my next question on um Albireo, what does it take to transition the company, you know, from discovery and preclinical work? Uh first, I guess, in the clinical research. What does that process look like?

Ron Cooper: 10:29

Well, it's hard, first of all, right? Because uh I said this is what I wanted to do. Never wish for what you want. Because you may get it you may get it in high doses. Look, I think about biotech a little bit like a fire, right? So you have a fire, you need a log, you need a spark, and you need oxygen, right? And if you don't have one of those, the fire doesn't work. It's the same thing with biotech, right? You need science, right? Uh you you need people, and and you need and you need money. Right. You need the funds to it. And I think what's really important in these companies is keeping those cycles in sync. So in this case, I would say if I was assessing Albireo, the the uh development cycle was well ahead, but the financing cycle was back line, and the human capital cycle was in behind. So the job one to me was how do we fund this company properly and how do we get the right experts for the stage of company uh that we were at. We were you know, we're transitioning into a development company. These are different capabilities, different types of people that you need. So that's what I was focused on, getting things in sync. And I would say that for any biotech, you know, the reality of it is, you know, if you have too much science and not enough money, that's you know, you're probably gonna destroy value, right? Because you're gonna make some decisions that compromise your science. Similarly, if you have you know, if you have not enough science, your science is not developing the way you have, and your infrastructure is too big, you're gonna burn too much cash, right? So keeping things in sync as you're scaling an organization across your your your science and your development science, your uh your your financial situation and the um and the human capital is super important for all these biotechs.

Ben Comer: 12:25

Um a big part of a biotech CEO role is is fundraising, no surprise. Um I suspect that you probably didn't do a lot of that at BMS uh prior to uh joining uh Albireo. How did you and you mentioned you know that the science was in a good place? Uh it was the funding and the human capital pieces that needed to pick me up. Um how did you how did you do that? How did you bring the money in? How did you um, you know, figure out how to be a successful fundraiser?

Ron Cooper: 12:57

Well, again, as I said, never wish for what you want because you may get it, right? You know, when you're in a big pharma company, you say, well, we don't have enough resource. You know, we're we're battling for budget and the right. The reality of it is, you know, with revenues, you're almost you almost have a money tree that you that that you go to. Being a non-revenue generating company, you've got to figure it out. In my first two years at Albireo, I did seven different financial transactions. Probably of those seven, six I'd never heard of before I'd started. Right. Um, and so I I think really the lesson for all of us as as um as as biotech executives and leaders, your job as the CEO is to make sure number one, the company has a good strategy, number two, that you have the funds to continue. And then so to me, I've always lived with the philosophy of you just keep going forward as much as possible. And so I was really grateful to our board, I was really grateful to a number of investors. But at the end of the day, it really is wearing out your shoe leather, right? You just have to really work hard, knock on, knock on doors, continue to refine your story, try and compel individuals and look at just different ways of funding your company. You know, over my career, you know, I have raised well over a billion dollars, but I would say in that billion dollars, you know, around half of that has been non-dilutive capital. So you have to be both creative and you both and you have to actually work hard at these solutions.

Ben Comer: 14:35

You've mentioned uh story a couple of times and refining your story. I think it's a a piece of of company growth and development that is not always talked about as much, but it uh strikes me as crucially important, particularly when you're out, you know, making the case uh to investors. You know, you I think you started out in in marketing. Uh, I think you're probably very familiar with how important the story is. What was the story that um that you wanted to tell with uh Albireo and how did you how did you land on it?

Ron Cooper: 15:09

Well, you're absolutely right, right? You know, if you kind of look for all your stakeholders, right? You know, we all have busy lives, there's a lot coming at us, right? And to break through the noise, you have to be compelling and you have to be clear, right? And I think in the case with Albireo, it sort of starts off with, what is this unmet medical need, right? And if you help people understand, you know, the patient impact, what's happening to these families, what's happening to these children, right? That's the first thing that says, okay, that makes you know, there is an unmet medical need here. The second thing is with clinical data, helping to understand that the technology that you have provides a solution for them. And then I think the third thing, and I and I take a great deal of pride in this, you know, for your stakeholders, you need to have a reputation of somebody that actually delivers. It's one thing to say what you're going to do, but it's another thing to do what you do. If you build a pattern of execution and delivering against your commitments, that makes the story have a beginning, middle, and end. Right. And I always think about stories like chapters in books, right? If I asked you, Ben, to read a book and say, start at chapter 10 and move to chapter two, and then you know, go to one and finish in chapter seven, you're gonna say, I don't understand what's going on here, right? Our responsibilities as CEOs and leaders of organizations is tell the story in a compelling manner, but in a logical manner, where people go chapter one, two, three, beginning, middle, and end.

Ben Comer: 16:44

You also took Albireo public um talking about fundraising. Uh, was that your first experience uh up close and personal with an IPO? And and at what point did you decide that that was necessary? Uh and I guess how did you decide that? Did you know in the process of scaling, you've talked about these cycles, uh moving forward with the science, raising funds, human capital. Um, what are I guess was the the trigger um for you with uh Albireo to take the company public? Well, now I'm gonna really tell you a war story here.

Ron Cooper: 17:20

All right, let's here is the real war story. Um, because it's much more complicated that goes into those seven deals that we did. You know, in in the summer 2015, I started with Albireo. I had my first board meeting. Uh, I'd spent you know, multiple weeks in Sweden. We as a team said, okay, where are we? What are we going, what are we going to do? And I think 10 days in my board said we should go bump again. And I was like, I thought, whoa, I thought we were gonna do that sometime, sometime next year. And to their credit, a lot of the board members were experienced um biopharma folks, and the market was terrific, right? So I was like, boy, that's an important piece, of course. Yeah, which I did I wasn't aware of. The market that at that time was really good, right? So it was naive of me. Uh and so then I said, Boy, boy, you know, what are we we I don't think the company's ready for this, okay? But I understand and you gotta we're in biotech, you gotta seize the opportunity. And so I talked to my chairman and he said, Well, go talk to some banks, right? And see what they said. Uh we talked to some banks and then, yeah, absolutely. You have enough science, you have all this. This is really good. What stage of development were you in at that point? You know, we were we were finished phase one and we had some early phase two data, okay, open label phase two data. See, terrific, right? And then I said, Okay, I'm not still not sure about this, right? So in the summer of 2015, we trot out, we meet a bunch of investors, and they're like, this is a great idea. Okay, we're ready to roll, right? So we said, We're gonna we're gonna become public. Then, you know, you know, now getting back in into history, a little thing happened called Martin Shkreli, right? And a little thing happened called Hillary Hillary Clinton. We got all ready to go public, and those investors that were so enthusiastic in the summer of 2015, in September of 2015, didn't even want to take our calls, right? And uh, and so unfortunately, um you we were get we were ready to go, and we just said there no IPOs are are going through. No IPOs. So we're like, what do we do? Right, getting back to keeping our financial cycle in sync, right? So then we I looked for some alternate um alternate approaches, and they're we they cut us uh you know a very long story short. We uh uh we became public to a reverse merger at the time. And that brought us, we merged into a company that had cash that brought us some cash, and then later on we were able to do a fundraising on the back of that, and that got the company up and going. So we almost our company Albireo, there were two. Times where we almost died. We got down to two weeks of cash, right? And we were like, what are we going to do? But by by being patient focused, by thinking of the urgency of that and being creative with our fundraising, we were able to kind of come through those crucible moments and create a lot of value.

Ben Comer: 20:18

I want to get to enGene, but before we leave Albireo, I know that some listeners of the Business of Biotech will be interested in hearing about a little bit about the Ipsen acquisition. Maybe just in terms of tips that you would offer to leaders and boards of biotechs who are looking for an acquisition or hoping for an acquisition. Are there things that they can do to help you know give themselves a better chance of that or facilitate an actual deal?

Ron Cooper: 20:51

Yeah, I think there are really two things for for individuals to think about. I think the number one thing is that in any sort of deal, you want to be in a position of strike, right? So if you can find a way that you can do this on your own and create value. So you're not dependent on an acquisition, that's probably the strongest position. So whatever you can do to think of financing the company, DC, find a way to create value to go forward on your own. Because if you can go on your own, that's a greater resistance strike. In our case, you saw you know there were overtures at different time frames, but the real well the reality is when we land up launching in the US, launching in in Europe, had a show-by story, right? So I think it's really important to say you've got plan A. You know, you know, and the saying is, you know, companies are not sold, they're bought. Right. You got to create value, whatever that is, number one. And then I think number two, if you're a public company, you have fiduciary responsibility for both patients and your shareholders to create as much value as possible. Uh but you know, our our big pharma colleagues, they've got a lot to think about, right? And it's also then your responsibility to keep them up to date, right? Because the reality of it is when these transactions occur, it happens very quickly. You want to create the most value for your organization. You want to have multiple companies. In the case of Al bireo, there were four companies bidding for us at one time, right?

Ben Comer: 22:20

So were you updating those companies? Were you providing proactively updates to potential suitors even before you know those talks began?

Ron Cooper: 22:29

You always need to keep as many doors open. And so for companies to act quickly, they need to keep in sync. If a company is way behind understanding, because remember, when companies acquire things, it's not just the clinical data. There's probably five key things they really need to understand. So spending time with help people understanding your patent situation, your manufacturing situation, your preclinical situation, the you know, what your business model looks like, and then what the clinical data is. It's just not the clinical data. And that's a lot to do. So updating people on things like manufacturing and those types of things. So keeping everybody up to date so that when something happens, in the case of Albireo, we didn't have one suitor, we had four. My responsibility is to do the best thing for our stakeholders, including patients, our employees, and our shareholders, that creates knowledgeable individuals to create the most value. So I would say, you know, it's it's sort of a balance. Companies not for sale, because you should be able to do it on your own. At the same time, your responsibility is to make sure stakeholders are in sync with you in case things change.

Ben Comer: 23:37

I've encountered uh several executives just in the course of doing this podcast who have talked about, you know, not wanting to become a commercial organization, you know, taking a drug up and in some cases not even really wanting to do the latest stage trials. Do you do you think that's a mistake? And I I've also talked to others, probably more so, who said, you know, you work, you continue to work as if you're gonna commercialize this drug, at least in the US, or in particular if it's a rare disease, at least in the US, and if something happens, uh you can be opportunistic. Great. But I I have encountered a number of CEOs who who have said, uh, we don't want to do that. You know, we're gonna develop this drug and and we're gonna um partner, we're gonna sell it. Uh what do you think about that as a as a strategy?

Ron Cooper: 24:29

I think your job as a CEO is to create value for your stakeholders. Um and to create value for stakeholders, you need to have optionality, right? And so, you know, I I would be in the camp of you need to see if there's a way that you can launch your product, whether it and there are lots of challenges to go with that. So I think you know, for some folks they find that just too daunting, but that requires a different mindset, it requires different, and maybe the CEO's not the right CEO for that circumstance, right? Which are difficult things for people, you know, to uh to accept. Yeah. However, there are ways to commercialize that are that are viable even in very expensive situations and commercialize with partnerships, right? Uh you can commercialize in in focusing on a niche group of individuals. I think probably to me the issue is more about expertise and about risk management. You know, there are some indications where it's very expensive to phase three and it's almost impossible to do so. But I think our responsibility as CEOs, like I said before, you must have different options to make the company go forward. So I would encourage companies to find ways to have a goal-alone strategy, even if it's a narrow one.

Ben Comer: 25:44

Yeah. I mean, you've spoken about the the real difficulty and challenge of scaling a company, but not just scaling, but transitioning from uh you know a preclinical environment into a uh a clinical uh development operation. Um, I I assume it's it's probably just as challenging uh to transition then into a a commercial organization. That's something you did. Which is which is more difficult, uh transitioning from a preclinical uh uh organization into a company conducting uh clinical trials, multi-site clinical trials, even, um, or uh a company who receives approval for a product and now needs to hit the ground running and and sell it in multiple markets.

Ron Cooper: 26:33

And you're effectively asking me which of my two hours I love more, right? They're both equally difficult for different reasons. And I think as you trans, you know, as you transition from discovery to development, right? I think to me the first pitfall is translation, right? Those companies that where you have separation and the folks in discovery create compounds and they throw it over the fence for development, they probably are not going to work out very well. Having really great translational capabilities to really understand which indication you're going to go to, having models to help predict the efficacy and humans and that sort of stuff, there's a lot of science and a lot of arts to that. And and the reality of it is we're in a smart person business, right? We have a lot of smart individuals, and smart individuals can often figure things out and scale with a company. However, it's a minority of individuals that can actually learn different capabilities and expertise. And the expertise to go from discovery to development, that mindset of clinical trials, right? Uh that mindset of going from more I'd call more of an innovation ideation culture to an engineering culture. And that that that goes with both your clinical development and your manufacturing. Manufacturing starts out a chemistry experiment. You're making one gram of something, but when you're starting to make you know hundreds of liters of something, that's a lot different, right? That's an engineering exercise, it's a different type of capability. And then then the transition from commer from from develop you know research development into commercial is even different, right? Because research and development is super complicated. There are so many things that can go wrong. Again, it's all about the science of doing it and the art of doing it. But commercialization is the exact same. There's no playbook that works all the time, right? And so you need a different sort of mindset that's much more externally focused, that's able to really, really understand the science of what you're doing for commercialization, the metrics, but also the art that goes with it. These are very difficult for organizations to transition. And so you need the right type of leadership each of these stages.

Ben Comer: 28:58

Uh, I'm going to follow up with you on manufacturing when we uh start talking about engineering and a uh unique uh FDA pilot program for manufacturing. So I want to ask you about CMC. Uh last thing on uh Albireo, though, and this is a business of biotech listeners will know this is something of a hobby horse of mine, but the priority review voucher program for rare pediatric diseases. Uh Albireo received one uh with the approval of Bylvay, I believe. Is that that correct? It's correct, yes. Um, sold it for, I think, $105 million. That's undiluted capital, a fantastic incentive uh for companies to develop um the drugs for these diseases that you're talking about that affect children uh that are so devastating and and many of them uh don't have um any available treatment. Uh that program, unfortunately, is not operating right now. It needs to be reauthorized uh by Congress uh and hasn't yet. So um I think you'll agree, Ron, uh here's to to hoping that that Congress can can get that done um sooner than later. Uh all right, we'll we'll move on to to enGene. Um what made you decide to join enGene? So uh Albireo was sold uh to Ipsen. Um you take a very short amount of time off, I think. Uh uh by 2024, you were installed as the leader and CEO uh of Engine. What made you decide to join uh that organization?

Ron Cooper: 30:31

Well, I guess for me, you know, as I think about my career right now in three chapters, right? Blue Bristol Meyer Squib, who's Big Pharma, it's my scale experience. I look at my Albireo, you know, and then retirement one, right? And then my Albireo experience, what I was what I would call a soup to nuts, uh real interesting soup to nuts entrepreneurial experience, right? Right from the sort of early private to selling the company. You caught the entrepreneurial bug. Yeah, I did, I did. And then, you know, frankly, retirement two, I really enjoyed it. It was a little, it was, you know, it actually landed up being 15 months, right? Okay. Um however, however, you're right, an entrepreneurial bug, right? And you know, in that time frame, I took the opportunity to kind of reflect on on what gives me energy, right? And and there are two things that give me energy, right? The the magic of drug discovery, development, and commercialization to me is a combination of the Easter Bunny and Santa Claus. Even to this day, I do not know how we go from the whiteboard with those chemical structures to helping a helping a child, helping a family, helping a community, helping a nation. I just think it's magical what we do. And knowing what we actually do and the risks that go with it and how many mistakes we can make, it excites me to make anything back to the patient. The second thing is, you know, I grew up playing team sports, right? When my team sports guy, the ultimate team sport is drug development, right? And frankly, I just miss being part of the team and looking at those big mounts and saying, how are we gonna get there and getting at the top of that mountain going, we did it. And then saying, Oh, there's another mountain, let's do it again. Yeah. As a related to enGene, what really got me excited was similar to Albireo. Number number one, I didn't know very much about bladder cancer. I was shocked at how poor the treatment options were. And then I was so delighted that the FDA said, look, we're gonna give guidance to say, let's lower the bar, one 100-ish patients study open label, you can get approval for. And I saw that this was a market that was going to go from analysts say from you know 2 billion to 20 billion. You want to be in something that's growing. I mean, we could be second thing is I looked at the profile of Dental Imaging. Like I said, I've launched dozens of products all over the world, right? And I looked at this profile and I said, boy, this product has efficacy. It it you know has a really good efficacy, it it looks like it's really well tolerated, and the handling and manufacturing aspect of this could really make a difference, right? And then the third thing was that you know Albireo was a little similar, sorry, the NG was similar to Albireo, in that this is a company that's an older company that had spent a lot of time really perfecting the platform, right? But wandering around a little bit, not in sync with their science, human capital, and financial really well-known opportunity to take it prime time, right? So that's what got me off the beach, and it's been terrific.

Ben Comer: 33:38

Did you how did you connect in with uh with enGene at that time? Did they reach out to you? Did you proactively find them and say, this looks like a company, you know, that I could really, really change and and help? Uh how did that happen?

Ron Cooper: 33:52

Well, you know, I've been in the industry for multiple years, right? Pretty big network, I bet. Pretty large network. And uh you look at the supply-demand curve for CEOs, favorite CEOs, and the supply-demand curve for experienced CEOs also tips in the it in in favor. So an opportunity to look at lots of interesting things. And then I think through through the network of individuals, we found each other, and it's worked out to riven.

Ben Comer: 34:19

Um you've talked a little bit about what's unique about uh enGene. I wanted to ask you about the significance of nonviral gene therapies. You also referenced handling, which I think is a big potential differentiator uh for this this product that you're developing. Um what can you say about that?

Ron Cooper: 34:37

Well, I have to say that first of all, you know, gene therapies and viral gene drip therapies have been a big advance. Big advance. Unfortunately, though, it's been a big advance for a limited number of patients with some shortcomings. So when you think of gene therapies, as terrific as they are, where are you limited? You're limited to how much genetic load you have package size. You're also limited because they cause immunogenicity and you can only, you know, it's a one and done situation. And then if you look at the commercial model, both the manufacturing costs and handling, you know, become almost prohibitive, right? Come to you come to enGene and you think about non-viral gene therapy, we solve all of those issues. Um and and we solve all these issues by going to the bladder as well. So in our case, we're not limited on packet size. We have three big genes in our payload. Very powerful. We re-dose our drug um because it's non-viral, we don't have the immunogenicity problem, and we deliver through through the bladder. So we re-dose our drug our drug week one and two, week five and six, rich repeat three times a year, and if you respond week one and two, you know, for the subsequent years. Fantastic. And then from a manufacturing perspective, our product uses four readily available ingredients. So as a result, we have relatively low cost of goods, and we're already manufacturing at scale. But because it's non-viral, we don't need any special circle, you know, special plant, we don't need any special solvents, uh, it's easy for us to handle. And when you think about the cost of the supply chain going from our manufacturer all the way to the practices, there's nothing special that we need, right? It's already there. And then when the doctor has it, they can take our product, it's just in the fridge in the freezer, right? So the so the non-viral aspect of Detalimogene and our platform making really unique, it's the only one, and it confers some really important advantages.

Ben Comer: 36:41

Um there are a couple of the, I think four maybe available therapies for bladder cancer. Uh you've suggested that that they're lacking. What um what is uh would you say is the key differentiator? And I know it's it's early, early days in clinical development for this product. I think you've hit probably hit on some of it already. Uh the the issues that make it easy to deliver. Um, in terms of, you know, from a patient perspective, uh, what what makes it different, do you think, or what's the potential there? Well, let's step back and let's think about these patients.

Ron Cooper: 37:16

Who are these patients? These patients are, you know, our dads or our grandfathers in general. Non-muscle invasive bladder cancer is on average 75-year-old men, smokers with comorbidities, right? Our market research says that the majority of these patients sit in the community. So they're not sitting in the big centers, they're sitting in in a in a community in a community setting. Standard care before was take your bladder out. Take your bladder. So you're talking about, you know. It's not an appealing process. Not an appealing process. You know, there you know, there's a high level of mortality associated with that surgery, 75-year-old corn or co-morbid gentlemen, anywhere 5-15% mortality. Yeah, um you land up with an ostomy s so so these are gentlemen now that that urinate through a bag, you lose your prostate, you probably lose sexual function. Nobody wants that. Nobody wants that. That's why the FDA kept up this guidance, right? Now, what's exciting about this guidance is you got new drugs. Excellent. The problem with these new drugs is that if you look at after a 12-month time frame, they have a complete response rate of somewhere between 20 to 40 percent. So none of these drugs have 80 to 90 percent efficacy, right? So better than taking your bladder out. So what's really exciting to me though is uh for these patients, it's you know this disease is a is a very serious disease. So carcinoma and situ is very bad, right? But it's slow. 20% progression over 10 years. Okay. About about in that range. So what are you trying to do? Recurrence is actually okay, still having cysts. You just don't want it to progress into the muscle or become a metastatic disease, right? So where the the market is transforming is then sequencing these agents, right? So people ask me, you know, what about your competition? Go, there's no competition. These are complementary medicines. All those medicines are going to use, we're gonna go from a $2 billion market to hopefully a $20 billion market and beyond, we're gonna help a lot of these individuals keep their bladders and hopefully die of old age, right? And what they will do, well what we anticipate happening is when one product burns out, the next one goes on, the next one, and we prevent uh progression. So then getting back to where does dental imaging fit in this because of the emerging competitive efficacy profile, which we have an open label study, so we have a good sense that you know uh that our anytime CR rate looks terrific. So we know it's an active product. Think about it from from in from a you know, so that's the first thing. Want a drug that works. Second thing, though, in the community, the community doctors value three things efficacy, so we're talking about efficacy, second thing, tolerability. Our product is AEs, or mostly are grade one and two, associated with catheterization, very few treatment interruptions. Most patients really don't notice that they have the product. And then the third thing goes back to the manufacturing handling part. If as a doctor, all you have to do is reach in the fridge, mix with water, instill the product, and on a clinical trial, they need to keep it in their bladder for an hour and they stay in the in the clinic because we need to collect their urine. But now you tap them on the back shoulder, go home, and you can urinate uh in into into your in your into your home restroom somewhere. Very easy for the patient, right? Whereas some of the others require pre-washes, they require bleaching because they're viruses, they require an insertion and removal of different devices. So dental imaging has this beautiful triangle that fits where the patients are in the community, you know, really a great emerging efficacy profile, tolerability profile, and then just an ease of handling that works great for the patients and for physicians.

Ben Comer: 41:20

Let's talk about manufacturing. Um, enGene was one of nine companies selected to participate uh in the FDA's chemistry, manufacturing and controls development and readiness pilot in manufacturing. Um, how how did that come about?

Ron Cooper: 41:36

Well, it's a real honor for us and really very helpful, right? So we so having received RMAT designation, which is the Regenerative Medicine designation, um CDRP is based upon, first of all, what is the innovation your technology and what is the clinical benefit? And as you said, it's one of nine, right? And the FDA in looking at our application granted us, so we're very grateful for that. We've enjoyed a really great, you know, uh uh partnership and dialogue with the FDA. And when you think about uh uh yeah, when you think about this therapeutic area or even drug uh development overall, manufacturing is something that people overlook. If you look at the most recent complete response letters, not been for clinical reasons, it's been manufacturing reasons. And so making sure that's in sync with your clinical cycle is important. So for us, what this allows is um a better dialogue with the FDA. Rather than waiting at the last minute, we sort of open everything up with them, we tell them what we're going to do, they look at it and they say more of this, less of that. We work back and forth through issues so that when we have the CMC pre-BLA meeting, we're all in sync when we give them exactly what they want, right? That to us reduces our chances of a click complete response letter. The other thing for us at enGene, this is a huge advantage for our organization because we have already pretty much completed our FDA validation batch, is otherwise referred to as PPQ. So we will be writing module three, which is submission document for manufacturing. So between getting through PPQ, having CDRP, it just lowers the risk of having a complete response letter. And then we land up with a product, as I said before, that has low cost of goods, easy to handle, very competitive manufacturing circumstance for us.

Ben Comer: 43:33

I want to ask you uh a follow-up on CMC for listeners of the business of biotech, um, you know, perhaps you're a a a leader of a a small startup, uh growing, progressing candidates. How should those folks think about CMC uh and you know when to invest in it?

Ron Cooper: 43:53

Early and take it serious, right? Because both if you're gonna commercialize to yourself or if you have a potential acquirer, the the worst thing that can happen to you is that you that a doctor likes your product, goes to prescribe it, and he can't get it. Yeah. You'll never change that out again. Second to that is if you if you land up with a CRL, you build your whole organization getting ready to launch, and on that last day you get a complete response letter because you are not fulfilling the FDA's requirement for manufacturing, they're both in disaster. That can break a company. That'll break a company, right? Because you're spending so much money to get ready, you're you're anticipating revenue. So while while while you know stakeholders don't really look as closely at your CMC, in reality, in the early parts of and particular depending on the technology, you're almost spending more money on CMC than you are on research or development. In fact, the CMC, and that's the problem sometimes, right? The CMC spend exceeds your clinical spend. And then as you as you get in later in development, you know, that starts to fade, right? Clinical goes up and then commercial goes up. So that's really tough for an emerging biotech to swallow. But I would encourage, first of all, making that investment. I would also encourage making sure that you understand that it goes from a chemistry experiment to an engineering exercise very quickly and you get the right expertise to get you there. I mean, in circumstances where you've had very smart, you know, usually what happens is you're a discovery person in a very small company, knows the chemistry, helps you with the manufacturing and can get you to a certain point. But professionalizing your CMC approach as early as possible, I would highly recommend it.

Ben Comer: 45:47

Okay. Um We are uh at JP Morgan, as I mentioned. Um one of the reasons I like attending this conference uh is because I I feel that it helps to set the agenda for the entire life sciences industry uh for the coming year. And I wanted to ask you, Ron, you know, at a macro kind of broad industry level, um, what are your thoughts right now about the health and life sciences sector uh going into the new year? I'm pretty excited. I'm actually really optimistic.

Ron Cooper: 46:18

Um and I'm optimistic for you know for for a number of reasons. You know, I I think it starts with if I if I if you kind of look at the last number of years, you know, they have been barren winter years for for the XBI, right? Yeah. Yeah, and and and you say, well, well, why? And why was, you know, particularly last year. I consider last year to be in two parts almost. Part one was the beginning part of the year. Right. And and the reality of it is, let's be honest, you know, we have big pharma and we have emerging biotechs, and big pharma sort of sets the table for our for the biopharmaceutical industry. And I really feel for my big pharma colleagues, because at the beginning of the year there were so many new things that they had to contend with. You know, remember, we have we have a we have a business that has a long life cycle life cycle. So you have to sort of assume that when you get to a stage, the situation is going to be something that will be conducive for your business. And I think a lot of our friends at Big Pharma, you know, were trying to figure their way through tariffs, MFM, R IRA and the like and getting a take on that. So I feel from the guy that was really tough to do. And they have to be careful about creating value for their business and making sure they take care of the business. Once I think they had a better sense of kind of what that would impact their business, they got back to what they really are good at, right? And what they're really good at is, you know, creating big drugs impacting patients, right? And and and creating growth in their companies. Most of our of our big pharma companies have created such beautiful products, but you know, they are coming off patents soon, and they've got to fill those patents, right? So I think they got back to what they do well, driving top-line growth, right, being more efficient, but then filling their pipelines. And I was really encouraged to see the number of acquisitions that occurred in the second half of the year. That gets the flywheel going, right? Those acquisitions with the biotech investors that are that are involved in those companies have to redeploy capital. That helps the rest of us. And then I think then that allows birthing of new companies and IPOs to come. So I I'm feeling very excited about 2026.

Ben Comer: 48:36

Are there any uh issues or or market dynamics that that you're watching uh um that you're kind of keeping track of, maybe um that could present a challenge this year? Tempering the optimism, but still optimistic.

Ron Cooper: 48:52

Yeah, I I would say, you know, to me the macro headwinds worried me. Yeah. You know, I I I I would say that you know you hear about the the potential AI bubble. Everybody believes it's gonna happen. They don't know if it's gonna be slow or big. The reality is of the magnificent that are dominance in the SP. You know, if there's a problem in that space, you know, in days gone past, money can be redeployed to other sectors or other geography, but they're so dominant across the percentage of the um the SP, I think that can have a major impact. Of course, some of these political geographic skirmishes can have an impact on the market. And some of the policy changes of the government are things that are our concern to me. Because long lead times, life cycle, we're assuming then we get to a particular stage and we will have to do something, but if the environment changes an awful lot, that's difficult. So policy changes. So when you start looking at policy changes that could affect the FDA, Medicaid, Medicare, reimbursement, these are very difficult for us to manage, right? Um things that could happen, you know, with um you know a bubble or these skirmishes can have an impact on our stock market and can have an impact on perhaps creating a recession and the like, and that funding environment becomes really difficult. But I think you know, on the other end of the scale, I feel really optimistic about you know the fact that big pharma is back to what they do well, that's got the wheel turning. I'm also very excited about you know the advances of AI. I think AI for us is going to help us, you know, we're an information industry, right? We need data and information, and we're just getting better. And you know, as I say to my team, you know, as we think about what we do, you know, I love our team and they're just so valuable. I want them, you know, anything where it requires their great minds and their beautiful emotions, I want them doing that. If you don't need emotion or big mind, we need AI to help us in that. So I'm pretty excited about these advances as well.

Ben Comer: 51:04

Uh well, just back to the, I guess, funding environment. You we we spoke last week, Ron, and you mentioned um that there can sometimes be a disconnect between raw Wall Street and reality. Uh and I wanted to ask, and I forget the exact context uh that you said that, but I wonder if you could explain what you meant that uh meant by that or or maybe why that is.

Ron Cooper: 51:27

Well, I I just believe Wall Street has a different job, right, than the job that we have about bringing drugs, drugs to market. And we coexist together, and I'm really grateful for our investors. But in the case of NG, you know, Wall Street is really good at math. Really good at math, right? And when you think about math, you know, in our case, folks are very focused in on response rates, complete response rates. And like good mathematician, higher is better. More is better. More is better when there's going to be a clear winner or loser. So in our case, where I said these drugs have about a 12-month complete response rate of somewhere between 20 to 40 percent. If there was something that was 80 to 90 percent, sure, you were also in a disease of where you had three months to live and nothing else matters. Sure, right? Um but for in our case, I think there's a disconnect from Wall Street to understanding that um obviously efficacy is important, but for where the patients are, now that we understand 80% are in the community, if you actually look at the choice drivers for community urologists, it is efficacy, it's tolerability, and it is how it fits in the practice flow for the patient and for and for the practice.

Ben Comer: 52:45

Um they're equally weighted. Meaning it's not overly cumbersome to administer.

Ron Cooper: 52:50

Administer, and it doesn't cost them a lot of money, it doesn't change the way you know these urology practices, you know, are increasingly are are owned by private equity, right? Yeah. They look through flows in their financial, if it costs them a lot of money, if they change, they need new personnel, they need more equipment, they have to use different rooms, they have to use PPE, that costs them money. Yeah. Right. Whereas if they ask them that slides in their flow, they really value that. So I think that I think you know what Wall Street thinks about is that you know, doctors are very focused on higher is better and efficacy is the only choice. In our case, if I ask with no disrespect to you know 10 community urologists, what is the 12-month CR rate of the four approved products? Uh likely none of them will get that correct, because they just don't think in those terms. Does this product work, right? Or not? Can I get it? Yes or no? Is it going to be easy for my patient and for me? When they think about one therapeutic era, they got to think about 50 of those, right? So that's why dental imaging with a you know emerging efficacy profile, really great tolerability, ease of handling in EUs, I think it's just gonna be a real asset for these patients. So that's a disconnect with Wall Street, and that's reflected, I think, in the evaluation of our company.

Ben Comer: 54:09

Final question. Um, your your top priority for for JP Morgan, and then maybe your top priority more generally for the company this year.

Ron Cooper: 54:18

Well, for JP Morgan, you know, there are some people that are bulls or bears for JP Morgan. I'm a real I'm a real bull for JP Morgan. Like you, it's the beginning of the year, and we have two pods of individuals here uh because it's just efficient. We have one pod that's really focusing on our investor stakeholders, making sure their updates in a very big year for us at NG. Right. Because this year we'll complete our pivotal uh study, have a day to read on the second half. We'll file the drug and we anticipate approval in 2027. Then we have a second pod that's focused on business development, to the point I had earlier. It's really important to have partners working with us to sustain the organization. So we've had a great JPM thus far, and I'm looking forward to putting another great JPM in the books.

Ben Comer: 55:06

Well, I'm glad to hear it. And uh, Ron, I'm glad to have met you in in person and had this opportunity. Really appreciate you taking the time to come on the show.

Ron Cooper: 55:14

Really enjoyed it. Uh, thanks for the opportunity to tell you a little bit more about enGene and the promise of detalimogene.

Ben Comer: 55:21

We've been speaking with Ron Cooper, CEO at enGene. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at life scienceleader.com. We'll see you next week, and thanks as always for listening.