Genprex bets on a one-time gene therapy for diabetes (Part 3 of 3)

0:05Welcome to Beyond Biotech and this third and final part of our series on GLP1s and the future of metabolic health. a series we're calling the metabolic moment in just a few years gop1s have become a phenomenon they've transformed how we treat diabetes and obesity created one of the biggest markets in pharma and sparked a cultural conversation that reaches far beyond the clinic now that market is shifting cheaper alternatives are coming new mechanisms are entering trials and some companies are aiming for something closer to a cure. So what happens next for patients, for the companies leading the field, and for the startups hoping to overtake them?

0:48Across three conversations, we'll follow the money, the science, and the people behind this metabolic moment.

1:13GLP-1 drugs have changed how we treat type 2 diabetes, but they manage the disease rather than repair what's broken. Genprex, a gene therapy company based in Austin, Texas, is taking a different approach. Its candidate, GPX002, uses an AAV vector to deliver two genes directly to the pancreas to restore beta cell function in both type 1 and type 2 diabetes. Earlier this year, the company presented preclinical data at ASGCT showing the therapy reversed high blood sugar in mouse models of type 2 diabetes. Now Genprex is preparing for IND enabling studies and has signed a manufacturing partner to help scale it up.

1:58Ahead of Diabetes Awareness Month, I spoke with Ryan Komfer, president and CEO of Genprex, about the company's move from cancer into diabetes, the reality of making gene therapies at scale, and where a potential one-time treatment could fit alongside GLP-1s. Ryan, welcome to Beyond Biotech. Thank you. Great to meet you. Ryan, you've been with Genprex since 2011, and you've been the president and CEO since 2024. How did you actually come to lead Genprex? What drew you to gene therapy in the first place? Yeah, so my background was in early stage technology investments and got involved in the kind of entrepreneurial startup community in Austin, Texas about 20 years ago.

2:49And happened to know the former CEO of publicly traded biotech at the time. and one of his scientific advisors for their company was a researcher at MD Anderson, Dr. Jack Roth. And so I came to know Dr. Roth quite well, and it was the culmination of his research at MD Anderson. He was a practicing thoracic surgeon and oncologist specifically treating lung cancer. And so he had spent his entire career researching lung cancer. And so this was the culmination of his research efforts. He has over a thousand publications to his name and is just recognized as a leader in the space. And so this project was his baby.

3:44And so I've known about it for some time and myself and a few others had the opportunity to license that technology out of MD Anderson back in 2009. At the time, I was involved in a number of other startup projects here in Austin. And so the original team kind of led the initial strategy, and I had always been kind of connected to it. But the founding CEO ended up getting cancer, unfortunately. and when that happened I spent more time working on the project because I understood the importance of it and you know slowly integrated more and more into the company we raised a lot of money in the in the private market with it and then took it public in 2018 and I've been along for the ride the whole time and you know unfortunately our our second CEO which was a good friend of mine and mentor, also got cancer.

4:49Thankfully, it wasn't life-limiting cancer, but he did have some complications and passed in 2024. And so the board appointed me to take over at that time. I mean, I think primarily because I understood exactly what was going on and I've been building the strategy for the company since inception. Now, as I understand it, Genprex started off in cancer therapeutics, but now you've moved into diabetes. How do you balance two pretty different therapeutic areas? Yeah, it's a great question. And, you know, balancing it is, you know, hard because we are a small team. I mean, we've been kind of a lean and mean operating company since we were founded.

5:33But we've always had, you know, interest in other technologies that could not only supplement our oncology program, but, you know, expand our programs as well. And we partnered with a lot of universities over the years. But balancing the two is certainly a challenge. Although, thankfully, you know, we outsource at this point, have outsourced almost all of the development work with our diabetes program at the University of Pittsburgh. So they've been a tremendous partner for us to explore the research and take the research to the next level. And thankfully, most of our team has been kind of focused on the oncology side, although we have some just really brilliant scientific minded people in our organization that are able to work in both areas.

6:18And so we're now just starting to transfer that technology. We noticed we announced here earlier in the year that we have transferred that technology out of Pittsburgh. Pittsburgh's still doing a ton of research for us to fine tune the diabetes program. But we've worked to expand our network of CDMOs and research organizations so we can optimize the diabetes constructs both in type 1 and type 2, get them through manufacturing channels so we can manufacture a drug in a consistent and reliable way and prep it for our talk studies that we hope to get into here soon. You mentioned the University of Pittsburgh, your gene therapy GPX-002 that was licensed in from the University of Pittsburgh back in 2020.

7:10Tell me how that deal actually came about. How did you come to learn about it and how did the deal get put together? Yeah, so it was actually somebody who was previously a consultant and friend of the company. We've had a lot of friends of the company over the years as being kind of a lean and mean entity. when we went public, we had, you know, four employees. And so, you know, we couldn't have really gotten to where we were today without some, you know, people that really believed in our science and some people that helped, you know, nudge us along, make connections, etc. And one of those individuals was a investor early on with us, invested a lot of money to get us to the point where we could go public.

7:55But he was also, he's just a brilliant, kind of a tech evaluator and has identified a number of new emerging and disruptive technologies in the market. And I honestly don't know how he came across the research at the University of Pittsburgh, but he was rather excited by it, presented it to myself and our former CEO. And we really did a deep dive on it. We dug into it and really, really liked the potential. And so we started talking with the University of Pittsburgh with Dr. Gittes in his lab and ultimately decided that we would like to pursue it. And so we initiated a license agreement with Pittsburgh, but also an important component of that license was to ensure that Dr.

8:44Gittes had all of the resources he needed at Pittsburgh to continue the research and expand it. And so one of the important parts of our kind of research agreements that we do with universities is giving some of these really brilliant scientists the opportunity to continue their work and expand on it. And once it gets to a point where, you know, there's a critical point that we can take that technology and transfer it and try to commercialize it, we will do that. But really, it's been valuable for us because we don't need to have, you know, scientific, you know, lab space. We can really rely on these, you know, brilliant scientists at universities and their labs to be able to do all the research that they need to.

9:34and then we helped kind of guide it from a strategic standpoint. And so that's how that came to be and we've continued that relationship, like I said, so they can fine-tune it. And now we've gotten to the point where they've handed off a lot of the research and we're ready to take it to the next level. You know, you also mentioned diabetes. When it comes to metabolic disease, it seems that GLP-1s have taken over the market in a lot of ways for metabolic disease, in particular for diabetes. What can a gene therapy offer that existing treatments can't? What sort of needs, patient needs, is it going to be able to meet?

10:08Yeah, it's, you know, I get that question so often when we're out at different conferences and investor conferences and even the general retail investors. And certainly GLPs have been hot. And, you know, Eli Lilly and Nova Nordisk, who traditionally are the two biggest insulin makers in the world, have been developing a number of these GLP-1s that have been very successful. Unfortunately, they really don't do much in the way of supporting type 1 diabetes. I mean, that's an autoimmune condition where the immune system is attacking your insulin cells. And so, you know, these GLP-1s really don't do anything to counteract that immune response.

10:56For type 2 diabetes, the fundamental issue there is that the insulin-producing beta cells have been so worn out and depleted from overusage from years of poor diet that they're just not producing insulin effectively. And so the GLP-1s are great in that most diabetes treatments and technologies that have existed out there are really related to trying to manage your type 2 diabetes. And GLP-1s assist in managing because they're limiting your dietary or they're essentially helping with dietary restrictions and requiring the body to need less insulin than they would otherwise. And so they're not really addressing the core issue with the beta cells being kind of exhausted.

11:52Rather, those beta cells just don't need to produce as much insulin as a result of the GLP-1s. And we believe that there is still a need fundamentally to be able to correct diabetes through a gene therapy process. And we know that industry shares that too. I mean, Novo Nordisk and Lilly, if you look at some of their acquisitions, they've spent a lot of money on stem cell-based approaches to try to bring new beta cells into the body to produce insulin. So the need to address diabetes at a core still exists. The GLP-1s are just kind of taking off the significant burden of insulin requirements in the type 2 market.

12:36Now, when it comes to your gene therapy, GPX002, you use an AAV vector to deliver genes directly into the pancreas. Can you just walk us through it? How does this target glucose levels? How does it address diabetes? What's the actual mechanism of action there? Yeah, that's a great question. So we have two different genes, the PDX1 gene and the MAF-A gene. And those two genes together have been found to be able to rejuvenate and create brand new insulin-producing beta cells. And they do this through taking alpha cells, which predominantly regulate glucose, and they trans-differentiate them. They convert them into these insulin-producing beta cells.

13:24This is particularly useful in type 1 diabetes because in type 1, as I mentioned, it's the body's immune system that's attacking those insulin-producing cells and wiping them out. And so for type 1, we are creating brand new beta cells that did not exist before, and those beta cells are able to produce endogenous insulin. So this is rather significant in the development of and treatment of type 1 diabetes. For type 2, and this goes to some data that we recently announced at ASGCT earlier this year, we've been saying for years that our thought, based on what we're seeing in the data, is that we're able to restore some of this loss function that these beta cells are missing because they've been overused for so long and they're not producing insulin quite effectively anymore.

14:20And so we didn't quite understand that as much as we do now. We've done a lot more research in type 2 over the last year. And the data that we have out specifically shows that if you take an animal and you're able to essentially induce type 2 diabetes and hyperglycemia through a significant high-fat diet. And so you're able to do that in an animal model. And then we're able to give our two genes, the PDX and MAF-A genes together. Even with that high-fat diet, they're able to produce insulin much more effectively and reduce and reverse hyperglycemia, which, you know, the high-fat diet continues, but we're able to reverse it.

15:11And so for us, the way we look at this is we've been saying for some time that we believe that we're restoring these insulin-producing beta cells, but we believe now that this data shows that we're actually restoring their function and are able to produce insulin effectively again. So these are the results that you presented at ASGCT this year. You must be preparing now for some future studies. Can you give us a peek into what these studies might actually look like, what you're hoping to prove? Yeah, so this recent study at ASGCT was really helpful for type 2. We haven't had a lot of type 2 data out up until that point.

15:56And so this was really important for us to show how we are actually restoring function in type 2. We have really strong data so far in type 1 showing that we are able to create new beta cell mass that didn't exist there previously. And also that that beta cell mass is producing insulin and is able to normalize glucose levels in type 1 diabetic animal models. And so now our focus is trying to refine the specific drug products. So we have the two genes, PDX1 and MAF-A. They will be part of the drug product. But in addition, we've been selecting the exact serotype for AAV and also the promoters that will help the PDX1 and MAF-A genes essentially do a much more efficient job of either converting the alpha cells to beta cells for type 1 or for type 2, restoring beta cells more effectively.

16:59And so we've been focused on a lot of research internally and with some CDMOs to determine what the optimal product constructs look like for both type 1 and type 2. And that's something that we hope to be able to share with the world on both what our product will be for type 1 and type 2 in the coming months. you know one of the other announcements that you had this year was a deal with a cdmo to start manufacturing your diabetes gene therapy program um there's all sorts of challenges that come with that we've spoken to people on the podcast before you've got problems of scale you've got problems of cost uh with gene therapies what are the sorts of things that you're keeping in mind as you're building this program as you're working with the cdmo particularly when you're talking about something like diabetes?

17:50Yeah, no great questions. So with our diabetes program, you know, the two genes that we are producing, we're producing essentially DNA plasmid for both. And that is very similar to how we produce in our oncology program for TUSC2, the tumor suppressor, we develop a DNA plasmid. The manufacturing associated with DNA plasmid is something that we understand very, very well, something that we've been doing and refining for the last 20 years. But we also knew that we would need to find an AAV manufacturer, which has become more commonplace in the CDMO space, but then also develop this specific construct in a way that is optimized with the DNA and with the promoters.

18:38And so we've worked with a CDMO that is able to allow us to fine tune some of these key components, the DNA plasmids, the promoter, and to optimize those constructs. And then we have identified CDMOs that have the scaling capability as well as the fill finish capability to produce in GMP standards that we will need for a clinical setting. And so we spent significant time finding, interviewing, checking out facilities for the right CDMO. And we believe that we have the right CDMO in place for our diabetes program to not only take us through the tox studies that we will be doing next once we select our constructs, but to move into actual clinical trials in humans.

19:30And to do that, you need to be able to find a manufacturer that can reproduce your material on a consistent level and do it in GMP standard for the FDA. And so it took us some time to figure that out. But we believe that the CDMO announcement that we made is really significant for the progress of the program. I want to come back to something you mentioned a couple of minutes ago. This is the state of GOP1s in the market. really they dominate headlines. We get pitches about them all the time. It's always in the news. And it also takes a lot of investor attention as well. How does a company like yours get people's attention with a gene therapy for diabetes in a space that just seems to have a whole lot of noise around GLP-1s?

20:18That's a great question. I think it's harder for us to capture attention out there, but ultimately there still is no functional cure for diabetes. And I think you feel that pain the most in type 1, where patients, they require insulin to survive, and GLP-1s will never touch that. So I think the biggest pain point in the market is certainly type 1. And you see a ton of investment poured in by the Eli Lilly's of the world, the Nova Nordisk of the world because, you know, there is a market there of patients that are completely underserved. And so I think it doesn't matter what the technology is, I think type one will always have that pain point that the market will, you know, look to try to solve.

21:11Now, you know, we're doing it in a slightly different way. If you look at the landscape and what, you know, the investments that Lilly and Novo and Sanofi and others have made in the space, and Vertex as well, a lot of the technologies right now that are being explored are stem cell-based approaches. They're essentially taking stem cells, converting them into insulin-producing beta cells, and then they're inserting them into the pancreas of the patients. And usually that requires some type of implantable device to do so. And Vertex has gotten some really great results from their stem cell-based approaches.

21:52And we think that it's likely stem cell-based approaches are the next kind of technology iteration or revolution in diabetes. But we think that gene therapies are the next iteration beyond that and really have the potential to be curative at some point in the future. And one of the key pieces of evidence that we point to of the impact of gene therapy is the mice models that we did for type 1 diabetes. You actually take an animal model and you induce type 1 diabetes by essentially wiping out all of the animal's insulin-producing cells. And so they don't have any functional beta cells in the animal to be able to produce insulin, and they require insulin to even survive.

22:38And so once we did that and we inserted our gene therapy, we found that immediately the insulin requirements essentially dropped and glucose levels normalized and they stayed normalized for a duration of about 15 to 16 weeks. that length of time in animal testing was really significant because if you look at comparable animal testing and stem cell based approaches, usually the stem cells that are placed back into the body are attacked by the immune system and killed within about 16 to 18 days. And so the fact that we're talking weeks as opposed to days, we believe already gives us a leg up. Now, Now, the question that everybody asked is, well, if you're delivering with an AAV, it has to be perfect, right?

23:29And so that's part of what we've been working on in the last year in kind of like a stealth mode is how do we optimize the constructs to be able to get more longer term durable responses of our gene therapy? And at American Diabetes Association last year, we announced that we are exploring the use of lipid nanoparticles, which we've done in our oncology program for years. But the data we announced there was really significant, and we believe that we're the first to be able to deliver an LNP directly to the pancreas and get a gene therapy exactly in the pancreas where it's meant to go in the islets and convert those islet alpha cells into beta cells.

24:15Now, we know that we need to increase conversion and do it in a way that, you know, we have much more longer term effects, like I said. But we believe that we are already dealing with kind of a leg up or step up on stem cell based approaches. And now it's about refining it. And so I think our AAV is the first step. You know, that's probably version 1.0 for our type 1 and type 2 treatments. But we're hopeful that down the road, you know, an LNP can be a version 2. because at least with an LNP-based approach, we can redose in type 1, and that gives us a leg up on the immune response. So tell me then about the positioning of what you're doing because the GLP-1s, they can help manage type 2 diabetes, but like you say, they're not going to the cause.

25:03They're not addressing that cause there. Do you see your therapy as a competitor? Is it a complement to GLP-1, or does it just target a very specific patient group within that type 2 diabetes world? Yeah, I mean, I think there could be arguments made that it probably could be viewed as a competitor. The way I see it is because GLP-1s are not addressing the core, ultimately, you know, something has to if we're going to create a treatment that cures, you know, type 1 or type 2. I do think that, and from a positioning standpoint, there are likely ways that we can come into the market that may be a little considered not as competitive focused or maybe more friendly to play with existing treatments.

25:55So for an example, there would be, you know, patients that are severely type 2 diabetic. While GLP-1s may help with, you know, curbing appetite and managing weight to produce, you know, less strain on the existing beta cells, that may be a population where we can actually make an impact to restoring some of their, you know, beta cell potential. And so I see that as a group where GLP-1s could be used in combination with a gene therapy like Genprex to really provide a much more comprehensive treatment outcome for a patient. For type 1, it's just a completely different story because the GLP-1s are never really going to have an impact on those patients.

26:42But there are treatments out there in the type 1 world, for instance, that are targeting patients that haven't completely become type 1 diabetics. They still have a few beta cells that are producing, but they're in kind of like a weakened state. And so Sanofi acquired a technology from PreventionBio about a year, maybe two years ago now, that essentially delays the onset of type 1. They're protecting those beta cells that have survived thus far. And they're essentially giving those beta cells another 15 to 18 months survival before the patient is completely dependent on insulin. Um, those are patients where we think that we could, you know, potentially combine our efforts with those drugs.

27:32So not only are, is, you know, Sanofi's drug, you know, allowing some protection around these existing beta cells, but what if we could, you know, add to the beta cell count? And so, you know, I, in those situations, I see our therapies as being a good complementer in some, something that could be potential collaboration opportunity for us in the future. You know, as this episode comes out, we're heading into Diabetes Awareness Month. You know, what do you, working in the field, what do you wish people understood a little bit more about diabetes and treating that disease today? Yeah, it's really complicated.

28:14I think one of the things that isn't talked about a lot that we see is that everybody experiences it a little bit differently. And I think that's also what makes having kind of an end-all, be-all, perfect, you know, silver bullet solution challenging, right? Because, you know, in the type 1 diabetes, as we talked about, there's patients that still have a little bit of beta cells. There's also patients that have no functioning beta cells and they require insulin every single day. And so there is kind of a big, wide range of people that have different types of diabetes. And because of that, I think there's a case to be made that there's a number of different treatments that need to be on the market to be able to give patients the exact treatment methodology that works for them.

29:14And so I'd argue that, you know, while a lot of people say, well, you know, you're competing with one drug or the other or the other. You know, the way I look at it is that every single company that's out there developing, we're all developing towards the same goal. You know, we want to see diabetes completely cured. And we think that we're not going to be the magic company that does it. I think we're going to be working together collectively with industry to move treatments forward so patients have, you know, the perfect recipe out there that they can go and find. And that's what, you know, I hope that we all strive towards.

29:52And, you know, a lot of times you just, you know, you hear people with this competitive mindset of, you know, who's going to be the winner. I would love to see the mindset shift to focus on the patients being the winners. It doesn't matter what the drug is. We need to find options for every single patient that has different conditions. So what sort of message then can you give to someone who's maybe recently been diagnosed with diabetes? Where's the treatment heading? Is this an optimistic time for you right now? I mean, I feel like, you know, I'm an optimistic person. And I think a lot of the people that we work with are very optimistic.

30:33And we have some just brilliant science minded people in our organization and our partners. You know, I also think that the nice thing about the diabetes community is there are just a ton of groups that offer support and connection. And, you know, You see that in diabetes and you don't see that in some other disease indications. And I think the biggest thing for the community is just increased awareness and education about what's out there. I hold a lot of optimism about where we're going. I think the GOP-1s have been absolutely great for the market. Competition is great for the market. You want to push people to try to get other drugs out there and see what works.

31:30Innovation is great ultimately for patients at the end of the day. A couple of times while you've been talking, you've used that word cure as if it might just be out there. Can you see that on the horizon? Is that something that we'll be looking for sooner rather than later? You know, I hope we get to it in diabetes. I think it's challenging because everybody has a slightly different bout with diabetes. But, you know, functional cures, I think, will happen in our lifetime. But it's just going to look a little different. I don't think there's going to be a silver bullet approach, but I think what will happen is we will have treatments that will get you 90, 95 percent of the way.

32:18And from a cure standpoint, that's good enough, at least for now. At some point, hopefully we can get that from 90 to 100 percent. But in my experience in developing technology, sometimes that last 5 to 10 percent takes the longest period of time. So if we can make the biggest impact on the front end and get people in the right direction, then we're really making an impact on the industry. And I think that's where GLPs have actually really helped a lot because they are part of this kind of diabetes management, weight management situation that reduces the burden or reduces the stress on the insulin-producing cells.

33:02and that's important, certainly. And so, you know, I think GOPs will continue to play a role there. We're just looking to do, you know, in a different way. Ryan, where can people learn a little bit more about the work that you're doing at Genprex? Yes, well, our website has a ton of information, genprex.com. You know, I think our investor relations slide deck, which there's actually an investor relation portion on our website, has a lot of information about our diabetes program and our oncology program. I'd even say that it's probably overwhelming because our slide deck is like 60 slides at this point.

33:46But we have just a ton of research supporting our science and our technologies. And so I'd encourage that to be kind of the first start. And then we also have a bibliography section on our website. If you're a science nerd, like some of the people in our organization, there's just tons of papers that you could follow up on. But we enjoy talking with different groups, industry partners, you know, about our science. We, you know, me or some of our scientific minded people, our chief medical officer or others, love to geek out on this stuff. So always willing to talk about it. Ryan, we'll add those links to the show notes.

34:26I want to thank you for joining us today on Beyond Biotech. All right. Thank you. Appreciate you having us. That's it for this episode. Don't forget to check out all the latest news and analysis at labiotech.eu. I hope wherever you are in the world, you have a great week ahead. Thanks for listening, and I hope you'll join us again next time for another Beyond Biotech.

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