Hi, this is Paul Knight at KeyBanc. I'm the Life Sciences analyst following Maravai in the Life Sciences industry. We have today Dr. Kate Broderick, Chief Innovation Officer at Maravai, Trey Martin, CEO. And I would assume we have Debra Hart here as well, but thank you for being here. Trey, I don't know if you wanted to say a few opening comments, and then we go into Q&A. But for Q&A, you know what attendees can do as we sit here with 32 and counting on the live usage, you can raise your hand, shoot me a question through the webcast, or email at paul.r.knight@key.com. So with that, Trey, I'll let you start it.
Okay. Well, thanks, Paul, for having Dr. Broderick and I here today. My financial wingman, Kevin, is in another hemisphere on a honeymoon, so I will pinch hit on the financial side in addition to the strategic and operational stuff. But I'm glad to have Kate with me today as well. We have come off of a nice quarter in Q4, starting to see some stabilization in our industry and have plenty of reasons for optimism. We are, of course, toward the tail end here of Q1 and won't be talking about that, but happy to answer any questions about Q4, the year 2023, and then the longer term where Maravai is headed.
Great. Kate, I think it would be a great time for you to speak. We met you at the Analyst Day in New York, but I think the real question of the day on Maravai and even in the overall industry is where are we with the development of mRNA therapeutics, vaccines? I think that's what the market's searching for, is clues as to what's next in mRNA.
Yeah, thank you so much, Paul. It's a pleasure to be here. Absolutely. And Paul, I get asked that question a lot. Is there a future post-COVID? And the answer is the future is incredible. We only need to look to last year to see the first-ever CRISPR approval from Vertex. And obviously, that uses RNA components both for the guide strand, the sort of kind of map for where the therapeutics need to be applied, and the molecular scissors, the nucleases can be applied in an RNA format as well. We also saw the first-ever approval of a self-amplifying RNA vaccine, so similar to mRNA, but with some slight modifications.
And then, of course, we see a huge diversification of the application of mRNA, not just, of course, in the obvious infectious disease pipeline areas, although we see a lot of activity looking for next-generation COVID vaccines, of course, but also looking at potential opportunities to improve the flu vaccine. RSV is obviously an obvious one. And then there's many, many others. But in addition to that, there's some really exciting data coming out on the use of mRNA as a personalized vaccine target for oncology, of course, treatment options, and also the application of mRNA for use in protein replacement, for instance, therapies as well. So really, the future is very bright because it is so diverse and because RNA is such a molecule that can be applied in so many different settings, really, that the world is the oyster for the application.
I thought, I think, some of us were thinking that maybe we'd see a vaccine, a combination flu/COVID vaccine. Is that still something that might be one of the near-term treatments we might see approved using mRNA? Or what do you think will be next in terms of modality or treatment?
Yeah, that's a huge plus for RNA-applied technologies as the ability to kind of cocktail different vaccines, essentially, into a single shot. And that's hugely beneficial from a patient compliance perspective for so many reasons. So yes, I think we can definitely imagine in the future a lot of the pediatric vaccines to be combined in that format. I think a sort of near-term win would definitely be a flu/COVID/RSV. And of course, there's many working on that opportunity. And then even more elaborate, you could imagine things like Ebola, some of the hemorrhagic fevers all being combined so that people don't have to be immunized multiple times. So I think that's a very realistic goal in the near term.
Flanders, I know Flanders 1 had some commitments that start to run into, I think they began in the latter part of 2024 this year. Can you talk to is it stage two customer? Is it stage three? And then talk to the kind of stage three customer count as well overall.
Sure. So Flanders 1 is specifically the GMP late commercial stage production facility for chemistry. Flanders 2 is specific to in vitro transcription of mRNA, so mRNA services and late-stage clinicals. And we announced in the quarter that we have commitments for actually both and will be fully operational and running customer material here in the first half for Flanders 1 and really in second and third quarter for Flanders 2. So it's been a long period. You don't just tilt up a late-stage GMP facility quickly. This has been a multi-year capital investment, and we're really glad to see that coming to a close. We've actually been occupying both buildings since the latter half of last year. And really, this is now about engineering runs, validation, and actual customer product here in the next few quarters. So that's pretty exciting.
As you look, I know there's The Antibody Society in America. There's the Alliance for Regenerative Medicine. I think I've talked to you about a group centered around mRNA. What's your feeling? Is that group starting to get good data on where we are with pipeline, Trey?
Yeah. So the advocacy is just starting. If you think about what happened in mRNA that is very different than all other historical pharmaceutical modalities, there was not a, let's say, not a very large pipeline of phase one, two, three mRNA pre-pandemic. There was fabulous work that had been done for decades to try to make the opportunity to realize mRNA drugs a reality. But there was some last-mile work to do that was done incredibly well during the pandemic to skip over, let's say, that long build of methodical pipeline for drugs to go to billions of doses of prophylactic vaccine for COVID. And the opportunity we see here is to build the infrastructure that would normally have built before that happens. And that's one of the reasons you hear us talking about focusing on discovery.
But that ecosystem, it has not established yet like it would have traditionally. And the same can be said for advocacy groups. The good news is that we fast-forwarded to the end to multiple billions of doses of vaccine showed safety and efficacy and showed the response time that mRNA will become known for. And that enables things that are completely different than infectious disease, like personalized oncology. Though the industry is relatively new, the good news is that we know that it works at the end. So now it's about filling in, as you say, advocacy, awareness, and in our case, the ecosystem of support for products and services from the early stages all the way through the end.
Right. Ironically, probably one of the pushbacks on COVID vaccine was that it was so quickly developed.
And that's something that will take, certainly, as you say, advocacy and awareness for the public to understand that an mRNA fundamentally looks the same, whether it is a neoantigen for a COVID vaccine or for the combos you and Kate were just discussing with COVID, flu, RSV, all those options, or for an NF1 patient in a personalized oncology vaccine or as a protein replacement therapy. The mRNA fundamentally is made the same way. It's a very efficient process. It's very quick. The difference between all those different applications is simply the sequence, the order of bases A, G, C, and U. That's why it's so powerful for pandemic response, but also why it can be used in a completely novel way to personalize therapies in timescales of weeks or months rather than years.
Isn't the safety profile just so far proven to be super compelling, Kate?
Yeah, really, you couldn't have asked for a cleaner safety profile from the approved products that are out there. I mean, of course, you get the injection site reactions. We've probably all, everybody in the call, experienced something similar to that post-COVID. But really, so far, the safety profiles have been really, really quite admirable.
And then, Kate, I think a thing we've been trying to follow over the years here with Maravai is CleanCap has certainly proved to have many advantages. Getting mRNA active longer in the cytoplasm, perhaps in other modalities. Manufacturing seems to be less chemical content. It seems like you've been presenting a case that CleanCap has a lot of advantages. Do those advantages seem to increase? And if so, why don't we see a conversion over to CleanCap more and more? Or are we, and we just don't see it?
I think, Paul, it's not a coincidence that three out of the four approved RNA products use a CleanCap. So I think that's something we're incredibly proud of, but also speaks to the strength of the CleanCap technology, right, is that's how those approved products using that technology have really shown those incredible results. And I think certainly, as we look in that, I can't speak to what other developers are doing. Of course, I'm not privy to that work. But certainly, when you look in the literature at scientific conferences and such like, you can really see an interest in moving towards that co-transcriptional capping modality, which is CleanCap, because it gives you that plasticity to kind of change that cap, Paul. I think CleanCap worked amazing, of course, for COVID.
But as we talk about what a therapeutic for an oncology target might look like, perhaps the cap looks different. And what CleanCap allows you to do is make chemical modifications to that cap to really come up with a tailored, bespoke approach for each individual opportunity or disease indication. And so we're really at Maravai pushing extremely hard to build up that library of caps and other bases, modified bases, tails, etc., so that developers can come to see and kind of pool from the shelves to suit their very distinct application.
The question here is kind of in the same vein. What's the customer-determining factor to use CleanCap versus some other alternative?
Trey, do you want to take that, or?
Sure. Yeah. I mean, we have that situation in the industry I described where we fast-forwarded. We actually skipped to the end, and we're working our way backwards. So there are a couple legacy methods of adding the biologically active cap that still persist because they were the way they were the means of enablement for programs that started many years ago. As Kate described, the CleanCap IP franchise itself is both method and material. So there's a product, and we talk about the product sales. But the co-transcriptional capping IP is around the idea that you can add this very efficiently during the IVT reaction rather than after it, maintain higher purity and better yield throughout your process, and also save time.
But as Kate just highlighted, the flexibility that you get in making these reagents, which are nucleic acid chemistry reagents, is that we can make modifications. And what you've all seen that we've been talking about since we launched in May is the next generation of capping reagents M6, which not only gives you all the aforementioned benefits of a process improvement, but also adds functional advantage through really modifying the nucleic acid chemistry of the cap reagent itself. So the process improvements, the method is still there, but now we're in a new era, like Kate was saying, where we hope to have a whole catalog for developers to work through and hopefully find their best possible advantages. You described, Paul, being longer-lived. M6's advantage is that it adds. It's a higher efficiency protein expressor, so the translation is more efficient molecule for molecule.
So that's the first of what we hope are very many new tools to put in the tool chest for drug developers utilizing the framework of the CleanCap IP.
The indicated stability in markets, non-COVID is still down year-over-year, though. Is that really linked to the biotech funding cycle, Trey?
Well, COVID in and of itself is an entire story. There are different levels, I would say, of compliance and interest in different markets. We recently highlighted, very recently in our quarter, highlighted an enablement for a partner, Fujifilm, to produce vaccines in Japan, for example. We're also seeing that so these different markets have not only as a COVID-era hangover focused on supply chain security in their region, but also now you see very different market dynamics for compliance as far as COVID vaccines go. That said, you had already highlighted that the move and the enablement that mRNA brings to infectious disease is the ease and the efficiency of combining multiple indications in one shot or one dose. So we expect to see that grow.
We reported our third-party study of clinical programs in mRNA, and infectious disease at 40% is still the biggest category of that whole pipeline. 16% absolutely were COVID-linked. But then the next largest category is oncology, which is, of course, very different than infectious disease. And so I think it will benefit the industry when we see mRNA approvals that are outside of single modality or double bivalent, for example, COVID vaccines and into multivalent infectious disease vaccines and then non-infectious disease approvals. I think we'll really start to drive home this message that Kate and I are so excited about, which is that this is a platform for multiple types of medicine treatments and targets.
What portion is oncology, did you say, Trey?
What portion?
You mentioned a percentage.
Yeah. Yeah. Let me pull that out for you.
I think it was around 27%, was it, Trey?
Yeah, that's right. Yep, 26%. That's right.
Okay. Thank you.
Kate's got the good memory. We saw an increase in programs year-over-year of 40% and an increase proportionally. Our market share stayed flat. Our program number also increased 40% in this year-over-year comparison. Coming back to your original question, Paul, this is a function of relatively new industry pipelines and candidates that might have been chosen five to 10 years ago.
Right. Okay. And then I'm looking at you behind you. I can see one reason why you made the move to Southern California. The other is obviously a highly respected entity in IDT. What does Maravai look like in five years? Are you more than mRNA? What's your view of the profile?
Yeah. Well, my long history at IDT was one, really, of enabling. We talk here the front end of the funnel, winning in discovery because we see such an opportunity to build that part of the ecosystem in mRNA therapeutics. It's really a similar principle to say we need to make the best we need to make the best material for our customers possible. We need to do it as quickly as possible because the faster we can make great things, the faster the customer can use them, get their answer, and keep evolving to find the best possible medicines in this case. And I see that opportunity completely. Maravai is really a collection of some fantastic scientific founder-driven companies.
We are a collection of TriLink, which through CleanCap gets a lot of the press, particularly post-pandemic, but Cygnus, which is the company that comprises our Biologics Safety Testing reporting segment, 35-year industry category leader called Glen Research, and most recently, a category-leading enzyme provider called Alphazyme. So we are a collection of companies. We hope to have that collection grow over time. But they have coalesced really around the next generation of medicines. Cygnus QCs all 19 approved CAR-T cell and gene therapies. And of course, the Nucleic Acid Production segment is so named because it really focuses on, first of all, between the acquisitions of TriLink and Glen Research and most recently, MyChem, really the most talented collection of nucleic acid chemists that I've ever seen, and enabling specifically chemistry that goes right to therapeutic benefit.
I would say that's the possibility that motivated me, in addition to the palm trees and the weather behind you, to move to California a while ago. But we are still primarily a U.S. company. We have work to do to enable that front end of discovery, to change the expectations of developers for time, cost, and the power of the tools that we provide, and the opportunity to globalize these incredibly storied brands that comprise Maravai.
Has anyone seen palmetto trees in Scotland, Dr. Broderick?
You have because the Gulf Stream come down one side. So yes, you can occasionally see a palm tree through Durban.
Kate was also obviously a non-reluctant transplant here.
You had mentioned earlier Fujifilm. Can you talk about that relationship? I mean, will Fujifilm manufacture CleanCap in Japan? How will that work? And then ultimately, a question would be, is this material to revenue in a year or just takes longer?
Yeah, those are great questions. I appreciate them. So Fuji will not manufacture the CleanCap reagent. They're licensed. Again, that IP is broad around method and material. We will continue to manufacture the reagent. You can think of it from Maravai's perspective as an additional sales and distribution channel. And we've announced some of those in the past. We have an enablement program for value-added resellers who are CDMOs. We haven't historically announced a lot of them. Fuji was just important, again, because of the unique nature of the Japanese market and how this was an important regional enablement. But they will purchase the CleanCap reagent from Maravai. They're licensed to use it. We partner in the workflow that enables the most efficient use and the best process. But ultimately, downstream, royalty conversations would come ultimately with the drug developer themselves.
This is an enablement to increase access in a really, really important market.
Have we not seen one or two approvals in Japan utilizing CleanCap?
Yes.
What could we learn from Japan's success or the approval of mRNA products there? Is it they started earlier? What do you learn from watching those approvals in Japan?
Kate, I'll hand that to you because we were talking about this yesterday. So I know Kate is a big fan, actually.
Yeah. Japan have had a really proactive view, Paul, of new innovative technologies with a specific eye to the application of RNA. I think during the pandemic, they realized, frankly, they were really lacking in those areas. And so the government infused a huge amount of cash, I think JPY 8.2 billion, to really encourage the early R&D and then all the way through clinical and commercial development of innovative platforms, which primarily are utilizing RNA. And so you're starting to see the early fruits of that labor right now. And as you mentioned, Paul, there, reg authorities are very open to considering these new applications, which is a very, very positive position.
Right. I mean, I think the secret to BioNTech and Pfizer wasn't really a secret. It was they had started well before COVID, right?
Exactly. Exactly. Because you have to put that groundwork in upfront, right? You have to socialize the idea with the authorities, get your manufacturing in place. These things don't happen overnight.
Do you think everybody's kind of on board regulatory agency-wise most places, specifically Europe, U.S., Japan? It sounded like Japan is.
Absolutely. I mean, we're still working vociferously with the FDA here in the U.S. It's been a very positive interaction. I think they are really wanting to hear from developers and are utilizing that feedback to kind of shape their guidelines, which I think is a really positive way to move this technology forward.
I remember about a year ago or so, it was like from one of the industry conferences, maybe it was CPHI. I don't really recall. But mRNA was the most highlighted topic of research by a survey at this conference. Is there anything that would kind of dilute that level of interest over the last year? Is there anything that we could say negative that people are finding on mRNA that would diminish enthusiasm?
I would say the platform itself is clinically proven. And again, coming back to my comment earlier that we look forward to something orthogonal to infectious disease being approved. I would say the biggest potential negative is just perhaps an investor or public perception that it's a COVID vaccine, and that's all it is. It is a platform. It's the opportunity to express any protein of interest in any cell for protein replacement therapy, to be half of the reagents required for CRISPR gene editing, to program CAR-T cell therapies, and everywhere in between. It's a new platform, and we know that it has clinical safety and efficacy. We know it works. And now it's, again, just about building up that infrastructure. And so I would say the only risk is one of perception that it's simply a one-trick pony for a COVID vaccine. It's not that at all.
It's an entirely new platform from configurable, programmable medicine. We're super excited to be a part of it.
The last topic should be a little time spent on Biologics Safety Testing.
Yes, it should.
I'm sure that they've probably seen some of the spending slowdown that's affected the industry. So if you could just talk about what you're seeing in demand, are we pulling out of this, etc.?
Yeah. So obviously, with Cygnus, we're very proud of their participation in all 19 approved CAR-T cell and gene therapies. Basically, they come into the process as people are doing their process development and early preclinical and phase one work and stick with, obviously, the customer all the way through marketed medicines. So the interesting thing about the nuance about that is that they fit very well into our overall strategy of winning in discovery and being the customer's first choice early because if anything, there is more activity for Cygnus in program starts and scale-ups. They stay with the customer all the way through, but more kits, more collaboration, more service work happens in the early phase of that funnel. And so consequently, they see a slowdown in program starts, I would say, earlier than others do.
And we started to see that slowdown and that cautious customer behavior really in the second half of 2022. And we've answered several questions about the China factor for Cygnus, which is a much bigger part of the BST segment than it is the NAP segment. There was a tremendous amount of growth in their segment in China in 2021 and 2022. And that slowdown really was oh, sorry, there's an echo there. That slowdown was really a function that was seen in the second half of 2022. After six quarters, that story has stabilized tremendously. And we've seen pickup in the other geographies. So Cygnus has found some stability. They had their like so many of our peers and so many of our businesses, they had their first down year in their history last year.
We see that they are, like I say, stabilized and poised to return to growth here in the second half of this year.
I was creating a little feedback on my mute. Sorry. The last question, I would we hope that maybe this GLP-1 success globally will create a COVID effect and create more spending in the R&D market beyond GLP-1. You see any impact of this COVID dividend yet?
You mean the GLP-1 dividend?
Yeah. Is that cash flow emanating from GLP-1 starting to help out the industry yet?
I mean, I think it is a great thing, first of all, for what it does and how effective it is. A little bit like the mRNA vaccine story from COVID, I think it's a very appropriate analogy to bring attention and funding that would be directed into more diversified programs. Absolutely. I don't have a specific example where we have a GLP-1 provider saying, "We're going to take this money and put it in mRNA just yet." But I do think it's beneficial to show that we're breaking new ground in medicine here and solving very old problems in new ways. It's tremendously exciting. It should be beneficial to the entire industry.
Yeah. I guess the last question I would have is that starting around 2012 with the advent of CRISPR, it's kind of a delayed reaction. Four to five years later, we started to see this dramatic acceleration in biologic approvals at the FDA. Whether it's you, Trey, or Kate, when do you think the starting line began for mRNA? And do you think it's two years? When do you think we really start to see the emergence of mRNA treatments or just to be general about it?
Let you start, and then I'll wrap about that.
The history of mRNA in 60 seconds or less. Yeah.
Yeah.
Yeah.
Credits. Yeah. Go ahead.
Sorry, Trey. Yeah. There was, so I've been in this field for 20+ years, Paul. So there was a ton of work on, obviously, non-COVID applications, a lot of work done in animals to really kind of hone that technology because, as you probably remember, there was a lot of work to be done on the delivery side as well as on the manufacturing side. But what COVID did was just give us a boost, right, to move things faster through the clinic than, frankly, probably would have happened outside of that situation. And that was for a number of reasons, funding opportunities, government willingness, etc., etc. So Trey, I don't know if you want to add anything to that.
Yeah. We need to give credit to the people, including Nobel Prize winners recently, who did tremendous work for the last 20 years and fought a lot of skepticism that this would work. There was a flywheel turning for many, many years before COVID. And had there not been, it wouldn't have been close enough to take the bet that was taken that turned out to pay off, right? There's always a bunch of really important people and stories early on in this. And TriLink, our business that has CleanCap in it, was making custom mRNA nucleic acid chemistry for people in the early, mid-2000s. So it's been cooking for a while, and we're all thrilled with how it's turned out and the possibilities for the future there.
With that, I want to thank you, Dr. Broderick, and thank you, Trey, for your time today. Our participants, thanks as well.
Thank you, Paul. Thanks, everybody.
Thanks so much.
I'll stay on modern.