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Presented by Kymanox, Life Science Solutions is dedicated to accelerating understanding and advancing expertise in the life sciences industry. Focused on bringing industry insights to light, our podcast offers a platform where regulatory, scientific, and engineering experts share practical knowledge on overcoming the challenges of product development and commercialization. Episodes equip listeners with the latest on regulatory updates, market trends, cutting-edge technology, and more. Join us as we explore the journey of modern medicines, ensuring every product reaches its full potential in safety, quality, and accessibility.
Announcer- 00:00:04:
Welcome to Life Science Solutions, the podcast presented by Kymanox, where we explore the challenges, innovations, and future of our industry. In this episode, host Chris Adkins is joined by Gerry Farrell, a seasoned expert in the CDMO space with over two decades of experience, including leadership roles at Fujifilm Diosynth Biotechnology. Now, as an executive advisor at Kymanox, Gerry has seen the evolution of bioprocessing firsthand, from monoclonal antibodies to the complexities of gene therapy. To start, Chris is wondering about the general understanding of the manufacturing process in gene therapy and where early-stage companies often struggle. Here's Chris.
Chris - 00:00:46:
You guys obviously worked a lot in in the gene therapy space whenever you were you were down in College Station. What do you see, in terms of the products and the processes that were coming through from the various sponsor companies? Where were they at from kind of a process understanding, process characterization perspective? What was your kind of broad base observation for those folks?
Gerry - 00:01:13:
They run the whole gambit. I think a lot of the early stage companies, they have little characterization of the product or of the manufacturing process. And you know, they just believe that the product works and want to get into patients ASAP A lot of times, you know, they don't really have the funds to gather that information. So, you know, a lot of the process we saw, you know, were coming out of academia, some of the larger companies are more well-defined, but very basic processes. The big challenge we saw was on the analytics. The company's not being, as I said, don't have the funds to gather all of that initial data. So they end up with a mismatch of... Unreliable assays that don't tell them everything. And, you know, then with that amount of assays, it creates a burden for them. And for the CDMO. The analytics are the most critical part of the process. Having that data, a lot of people underestimate the time it takes to get those methods in place. I think for us, initially, we basically just need methods that are fit for purpose. But need to be robust enough that can be transferred to CDMOs.
Chris - 00:02:43:
Yeah. And it's tough because it doesn't feel like your analytical development directly, you know, it doesn't directly correlate to outputs of, you know, grams of protein or, you know, loaded capsids or whatever it might be. But it has such a such an impact on the understanding and the characterization of your manufacturing process.
Gerry - 00:03:01:
Yeah, it does. I think early on, it's important that you identify and document those CQAs, or what the quality attributes of your product are, and what methods are going to help you manage those through the process. You know, initially for many companies, this could just be potency and tire and safety. I think, what happens is people would just, you know, put a whole, you know, just shotgun approach and generate a whole lot of, you know, methods that. Generating conflicting information. Not really. It's not really adding a lot of value. And then add them to the timeline. Because, you know, to do analytics, you have to have products. So the analytics are always lagging behind the process. The more methods you have, the more maturity you need to develop these methods. Um, I think it's important just to follow your process. And as a quality evolves, as a technology evolves, then you get a better view. To where you stand. With your methods and, and but what they're telling you. Like you said initially, for us, too many methods are worse than too little in a sense because it's just the churn that it creates and the time that it adds to your own process.
Chris - 00:04:34:
That's really interesting on the analytical side. I'm curious. Obviously, you've been in the space long enough to be before gene therapy and even back to some of the earlier days of monoclonal antibody, not the very, very beginning. But do you see a parallel with where gene therapy is in terms of kind of the average development program that you see versus maybe what we saw for MAP processing 30 years ago? Or do you think it more just has to do with... Really kind of tight funding versus maybe a little bit more availability to do some of that requisite development work.
Gerry - 00:05:11:
I think the challenge with gene therapy at the moment is and just from attending the advanced therapies conference back in, back in January that there's. The processes are still being defined. Today, there's five or six different flavors of car keys. What are the best capsules? What are the best self-sorting devices? What tools are you going after? What expression systems are you using? With the antibodies. Not that the antibodies now would be considered a simple process, but back 20 years ago, it was more straightforward. You know, you had... You had your DG44 cell line and you had a couple of different variations on that. But your target was, well, we're at 500 megs. We need to get a gram and then we get four grams, five grams. So I think there's, you know, from... Development point of view. It's probably going to follow the same path, but I think there's a lot more moving parts, on the gene therapy side and the cell therapy side. Than what you had on the antibody side.
Chris - 00:06:19:
We've really just kind of ratcheted up the complexity, right? And, you know, I tell folks it's that the easy drugs to develop all got developed, you know, whether 20, 40, 50 years ago, right? Now we're left with harder and harder and smaller and smaller patient populations generally.
Gerry - 00:06:35:
Correct. And the antibodies are still a growing field as well. We've seen from the amount of capacity that's been put on the ground, like 3G plants put $8 billion on the ground. Samsung continue to grow and here in North Carolina, J&J and Amgen are putting big tanks in. So there's a... It continues to grow there.
Chris - 00:06:59:
Yeah. That's a good point that I want to touch on in a few minutes. I'm curious to kind of loop back. And as we're talking about, you know, early stage and startup companies, and, you know, we were, we were both at advanced therapies week, not that long ago. There's... There's a lot of kind of... Interest and growing optimism, I would say, right? You know, I mean, we're recording this here in early 2025. We still kind of feel like we're thawing out from an investor appetite perspective. You know, so do you think there's parallels with the need for better characterization and better development with what investors are looking for? Or do you think it's a bigger issue than maybe the specifics within the science and it's more just on the commercial and the kind of economic realities?
Gerry - 00:07:52:
I think a lot of it is the economic reality. You know, there was a lot of optimism at the conference, like people said, stuff's going to turn around, it's turning around. But, you know, you talk to individual people, they're also fighting, looking for funding. It seems that if you have something that's ready to be flipped, then you're getting the money. I think still there's not much money going into early stage.
Chris - 00:08:16:
Yeah.
Gerry - 00:08:16:
And I think part of, just from at the conference as well, A lot of people there were different tools, different approaches, different cell lines. Different ways for manufacturing capsids. So a lot of maybe not directly going out for indications, but building out those platforms. We have a platform that they can offer. I think it's going to be interesting over the next couple of years, how those platforms develop and which of those move forward. I think one thing I'd seen at that conference as well was the, I think it's the Gartner's hype cycle for gene therapy. So, you know, we've... I guess we've gone through the peak of inflated expectation. We had that, and now we're just coming out of the trough of disillusionment. On the slope of enlightenment, heading towards the plateau of productivity. Yeah, I think that was one of the – I don't know. I should probably get the credit of the person that put that together, but I'm not sure who they were. I just remember – It stuck in my mind, but you know, 5, 10 years ago it was, yes, it's great. It's great. Then we had COVID and we just, everything dropped away. Now I think it's starting to come back.
Chris - 00:09:35:
Yeah, yeah, yeah. And we have products on the market. We have successfully commercialized. Assets, you know, that there's a good number of them out there and we're seeing life change that's happening from them. Right. And especially they make incredible stories, right. It's much more convincing to put forth a curative story than maybe a vaccination based one, right. Where it's your success is someone not getting something, you know, or your success is controlling a chronic disease, right. Versus your success is truly curative and someone living who otherwise wouldn't.
Gerry - 00:10:12:
Right. Yeah, and I think there's a piece of marketing to be done around that as well. You've got the cost to go with that and how you sell that with the payers. It's good stories. But we've seen as well with a lot of the... Gene therapy Manufacturers have been cutting back. Thermal Fisher have closed down plants. Rensselaer have closed down plants. We're Resilience. I think some of that maybe goes back to that peak of that inflated expectations for a lot of people, you know, invested for a lot of CDMO space. On the ground. And some of this is probably just a normalization of capacity to meet the true demand that's out there. It's a tough field to be in. We saw that. Because you're treating such a small patient population, and then the process, the yields are so low from these processes still. So, you know, until we get to that stage where we've got to the, you know, process optimization that... You know, there's a big push towards platform. So if you have this platform, you've got the same expression system, your same character process is gone. After different indications. You're going to minimize your costs, minimize your development time.
Chris - 00:11:36:
Yeah, no, that makes sense, right? So, I mean, I think that's an interesting segue. You commented on the difficulties in the CDMO space. And it's interesting because you listed off some local, your local to kind of, let's say, the North Carolina ecosystem and some of the growth that's going on. And we've seen, you know, I can't remember how many, I want to say it was $10 or $11 billion in investment that came in last year for sites and expansions and things like that. Some of which is, you know, Fuji right here in Holly Springs and some of the other ones that you mentioned earlier. And then at the same time, we see CDMOs shuttering some capacity, right? We have seen over the last maybe half a decade here, again, just even locally. Folks, you know, shifting away from building out internal manufacturing capacity and shifting to CDMOs because funding got tight. What do you make of that in the current kind of assessment in the CDMO landscape where we see some folks growing in capacity? Some of this gets into, you know, traditional, you know, monoclonal antibody protein manufacturing versus gene therapy or cell therapy. But what's your kind of take on why we're seeing some folks be so successful and then some really having to reel things back in?
Gerry - 00:13:00:
So I think the success has been on the antibody side. Like all of the capacity and all the major investment in North Carolina in the past like that eight ten million dollars that you said There's all been into large tanks to produce anybody's Some of it's been the CDMO space with Fujifilm. A lot of it's two big investments by Amgen for their in-house projects and then J&J. I think where you were seeing the cutback has been on the... Gene therapy style and I think it hasn't progressed. As quickly as people expect it to progress. Than with, you know, there was an excessive capacity put on the ground for gene therapy space. And then someone as well as, you know. It's hard to make money at the gene therapy. So Lexatherma and Resilience are probably doing an ROI on what they're doing. On what they can make from the gene therapy compared to the... Antibody, you know, you can run. You can turn a batch of antibodies every four days and generate tons of material. It's the same thing, whereas the challenge of working on the gene therapy side, I think, is still a tough challenge.
Chris - 00:14:15:
Mm-hmm. Yeah. And it's also difficult because, you know, it's interesting, even on the antibody side, we see so much commercial scale capacity is being built. Right. I mean, CDMO and companies side. Right. We see some on the development side, but we certainly see more of a splash on the commercial side of things.
Gerry - 00:14:38:
Right. We do, and also on anybody's side, the – Process intensification, you know, there's companies out there offering, you know, continuous manufacturing for antibodies. The advantage of that, you've got a cap investment, so you have a 2K or a 4K bioreactor going through continuous purification. Um, you have low capital. Barrier to get in and then it's you know basically having the same output as um as those large tanks. I think one of the cool things about antibody is going to be to see how, you know, getting the cost of goods down, like when you get a $10 per gram, antibody. Which, you know, that's the stage I think antibody manufacturing is at now. It's all about cost of goods, and it's really a commodity. What's the best way to get those cost of goods down? You know, some are investing in the large tanks. Whereas on the other side, you have just Evotec have been out there with different process, continuous verification.
Chris - 00:15:51:
Yeah. I mean, I remember, I remember hooking up, you know, Repligen's ATF back, oh man, I don't know, 12 years ago. Right. And, you know, we were doing it in small, you know, single use, right. So, but, but really ramping up, ramping up density in our, in our N-1 reactor to then get into production, you know, the production reactor. So, yeah. And, you know, that brings me to my, to my next point. It's interesting how, and I kind of, I cut my teeth on the single use side of the industry. Right. And of course, then really went and sold single use technology and really fully drank the Kool-Aid and that was the future. And that was what everything was going to be in. And then of course, everything that we talked about earlier, that's being built all, you know, enormous stainless steel tanks and single use hasn't really gone beyond two or 3K. And those even still folks kind of raised their eyebrows out. Right. I mean, do you have any, any thoughts on what that breakdown is going to continue to look like? Do you think we've kind of settled in to, to what it's going to be? Or I don't know, everyone's every, everyone who's an operations person has an opinion about single use versus stainless. So what's yours? See, we'll let you offend some people.
Gerry - 00:17:02:
So, so, so for my personal opinion. Stainless steel just scares me. You're walking into those large stainless steel plants and just the scale and the cost. And one gasket goes awry and you drop a whole $10 million batch.
Chris - 00:17:19:
Yeah. It's more about the volume of production at any one go, right?
Gerry - 00:17:24:
Yeah. That's just personal opinion. Yeah, so I was like you, you know, whatever, 15, 20 years ago, we set what our single-use platform was going to be at Fujifilm. In my mind, stainless steel was a thing of the past. I think as antibodies become prevalent, it's growing. It's out there. The demand is out there. These drugs have taken off. So the blockbuster drugs, the biosimilars, it's the scale. You need the scale. For the cost of goods. I did think that we would have gone more towards perfusion. Because of the capital investment, like, you know, the amount of money, the billions and billions of dollars going into these stainless steel plants. Um, you know, so that, you know, The return on investment there is like a long, long time.
Gerry - 00:18:21:
Yeah, yeah, yeah. I mean, especially from a, from a, it's one thing from a, from a product sponsor perspective where you know you're going to have the market beholden to you for your product for X number of years, right, based on exclusivity. To me, it feels much more difficult from a CDMO side where you're, you're reliant on clients to sign up for this really large commercial scale, right?
Gerry - 00:18:44:
Correct, but I think that's a different, it's a different sales process for the CDMOs with the large tanks on the ground. Then you're talking about partnerships with large pharma. So you're getting into these large pharma companies. You have a view that are pipeline. You see it coming. So you're not selling 20K bioreactors four or five every day of the week. These are long-term partnerships.
Chris - 00:19:08:
They're long-term deals, right?
Gerry - 00:19:10:
Yeah. And you're not turning – you're maybe doing two or three products a year. So you're not turning them.
Chris - 00:19:17:
Yeah. Which makes it a lot easier operationally, right, as opposed to being in development and running 20 or whatever.
Gerry - 00:19:24:
Yeah. As you know, the changeover cost of that scale is just tremendous. But again, that's about – large companies putting those tanks on the ground, it's about partnerships.
Chris - 00:19:34:
Yeah.
Gerry - 00:19:34:
And they have a view to those partnerships and those deals with the large biopharma companies.
Chris - 00:19:41:
But I mean, it would make me nervous enough to build a facility for my own product that was in phase three. Right. Let alone CDMO build it for a client's product that's in phase three. Right. Because not all phase three files succeed. Right. There's an example here locally of a CDMO that built out a facility for one client and then the project failed. Right. So it's a pretty, pretty unfortunate. But that's the nature of, you know, taking the risk and maximizing your exclusivity window. And so.
Gerry - 00:20:11:
Yeah, and there's a lot of factors. You have the CDMOs have their models. You're thinking, okay, I've got one that's signed and sealed. There's a chance. You need a bunch of products sitting behind. Because as we know, something's going to go wrong with one or two of them.
Chris - 00:20:30:
Yeah. Yeah. Yeah. But it is interesting, you know, that we never, to your point around perfusion, right. We still have not you know, on the antibody side, we haven't gotten to the point that we've said, okay, let's, let's bring this back down from a sheer volume perspective, right. And work the perfusion angle more and the yield angle more to try to, but some of it, I guess is the, again, the, the, the regulatory inertia, right. We have a process that works and let's keep doing it.
Gerry - 00:21:00:
Yeah, you have a process that works and you have the large companies. Because again, it's the volume of material you're going to need as well. It's got to be, you know, you're looking for tons of material. A year. But you're right. I think it's the regulatory inertia. I think a lot of it is these large companies have their platform that they're, you know, all the products fit in this platform, that they're going around with it. It works.
Chris - 00:21:24:
They have all the infrastructure for it right they have their lab they have their you know scale-ups and then they're gonna they're gonna make everyone hit the mold?
Gerry - 00:21:32:
Yeah, which- They do, and then you can see it outsourced in the CD modes, but then you have the likes of Amgen and J&J putting extra tanks on the ground, so it's sort of... If you're going to put new stuff on the ground, why not? Change the process, you know, go to something that's got less of a capital. I've kept the barrier. I don't know. It's I've gone back and forth about that for years. For me, single use makes the most sense. That's what I grew up with. Well, I was not that young. We started off in stainless steel. But again, if you want 20 gigs, 30 gigs of material, every week or every month and it's the big tanks make the sense if you have the funds to um build them on a manufacturer.
Chris - 00:22:23:
Yeah. Yeah. So you've been there, you know, you've seen that kind of, let's say, the single use renaissance maybe, right? And, you know, obviously the perfusion technologies, are there some current technologies or solutions that you're seeing out there that you're keeping your eye on and you think are going to make a big splash in the space?
Gerry - 00:22:46:
Um, like there's just been a, just like the continuous purification. We have the various columns, multiple columns, just continuous purification of the perfusion bioreactors. Interesting to see how that plays out and if it does get a foothold. I think with that, that's going to bring down the cost of goods.
Chris - 00:23:08:
Yeah.
Gerry - 00:23:08:
You know, you have low operating costs, high yield. But yeah, on the antibody side, that's about it. The gene therapy, that's the more exciting side, right? I think.
Chris - 00:23:21:
Sure.
Gerry - 00:23:22:
You know, where that's going to go, where... You know, we start bringing AI and machine learning start coming into those processes.
Chris - 00:23:31:
Yeah.
Gerry - 00:23:32:
Like we used to have a colleague of mine from years ago, and he used to talk about... Dry Science. I'm not sure if it was unintended or not, but his comment was, why are scientists turning bioreactors and running experiments? They should be sitting at their desks, building models, running programs, analyzing data. So, you know, I think that's where we're going to get to. You know, when you see, you know, you do all of your PD. As the models are built out and as the data is built and the data is fed back, you build out these models. You develop your process. On the computer. And then just hand it off to your tech transfer group.
Chris - 00:24:20:
Yeah.
Gerry - 00:24:20:
Yeah. Next step is do you get to try manufacturing?
Chris - 00:24:28:
Well, how far, you know, and you're starting to waver into the digital twin idea and things like that, right?
Gerry - 00:24:34:
Yeah, but they get into a stage where you take your engineering rounds, you take your shakedown rounds out of the picture with the data feedback that you have, all that stuff. I'm no expert on AI, but just reading.
Chris - 00:24:47:
As two operations guys, I'm sure this seems terrifying to us. I can't imagine not having that engineering activity. I can still tell you how many deviations we had on our first GMP run, right? We did engineering runs.
Gerry - 00:25:00:
Right, but that's maybe not full to that, but using this machine learning, this data feedback to prevent or predict deviations. As you're building data, as you're building models.
Chris - 00:25:13:
Yeah. Yeah. There's a tremendous amount of work on the discovery side, right?
Gerry - 00:25:17:
Yeah.
Chris - 00:25:18:
For molecule discovery and things like that, but we're still not, I don't know how much they improve the percentages. I'm sure there's some marketing material out there for some drug discovery, AI/ML companies that would tell you, but it's still a challenge to simulate a full biological system, whether it's the human body or it's the process, right?
Gerry - 00:25:37:
Yeah, of course it is, but that's what we're getting to. As you build more information, if you get the scientists, the manufacturing guys, the clinicians together, and even the patients, and you start building those models, all of that data is fed back. How far can you go with reduced clinical trials, reduced prep time, reduced manufacturing? Because today, it's the cost of goods on the gene therapy side that's what's killing everybody. So, you know, how you get those costs of goods down, you know, when it's the platform processes. And how you manage that. And platforms go back and forth, you know, they're in again, they're... Out again but I think it is you know once You know, today there are so many different versions of platforms out there. What's the best platform? What's the DG44 of the year? Gene therapy side.
Chris - 00:26:37:
What's going to ultimately win, right? We're still in a phase where the race is still actively being run, right? I think that's good. Anything else?
Gerry - 00:26:49:
I think one thing, back to the analytics, a lot of customers or sponsors don't take advantage of the CDMO. They tend to just dump the package on them. You go to CDMO because they have that level of experience. So take advantage of that when you're developing the package and what you need for your process.
Chris - 00:27:15:
Earlier. and?
Gerry - 00:27:17:
Yeah, because CDMO has shared ownership in the process, like reputable CDMOs. I'm sure there's, I don't mean to say there's non-reported, non-reported so you know out there. But just, you find a lot of time, you hear from the sponsor side, oh, there's a presentation about partnership and quality agreements, and all that stuff's critically important and you need it. But there's also a piece that you need to leverage experience. You're paying for that experience, so leverage that experience with the CDMO. And when they give input, then take it, because they've been down the path. They've seen the products go through, they've seen the regular approaches and what's... What's needed.
Chris - 00:28:02:
Yeah. Yeah. Yeah. If you're having to tell them exactly what to do all the time, we would say you probably haven't chosen the right CD.
Gerry - 00:28:08:
Yeah. Correct.
Chris - 00:28:09:
You either got them over their skis or, or something else worse. Right?
Gerry - 00:28:14:
Yeah.
Chris - 00:28:14:
So I would, I would, I would agree. So. Well, excellent. Well, Gerry, really appreciate the time. Thanks for joining us on the podcast today. And yeah, look forward to future conversations.
Gerry - 00:28:26:
Thank you, Chris, and join us.
Announcer - 00:28:31:
Thank you for tuning in to Life Science Solutions presented by Kymanox. A big thank you to today's guest, Gerry Farrell, for sharing his insights on the evolving CDMO landscape, the challenges of gene therapy manufacturing, and the future of bioprocessing. For more information on Kymanox and how we help bring life science products to market faster and more efficiently, visit kymanox.com. This episode was edited and produced by Walk West. Until next time, this is Life Science Solutions, where challenge meets innovation.