Hi. We're gonna start the Charles River Labs presentation here now. Anyway, thank you for joining us today. Like I said, we have Charles River here, CEO Jim Foster. We'll do a company presentation followed by Q&A, where you'll have a chance to ask questions. For now, I'll turn it over to Jim.
Thank you. Nice to be here. I have a little bit of laryngitis, but bear with me. Safe Harbor Reg G and quiet period statements. Give you eight seconds to read those. We have a portfolio that starts from early discovery all the way through drugs being approved and actually after market approval. I don't really like the term, but we increasingly have become a one-stop shop for our clients who really wanna. Everything's about speed. They want to work with as few research partners as possible, and they want us to have expertise to move the drugs forward as quickly as possible. They want us to be flexible in the way we work with them, both from a structural point of view and a pricing point of view.
They want us to add value, particularly our biotech clients, which is the preponderance of who we work with that really have very little internal infrastructure. Our LTM revenue is $3.8 billion. Wouldn't surprise you that our revenue is primarily from North America, about 70%. I suspect that won't change materially over any period of time, given the fact that biotech is principally a U.S. or North American phenomenon. Our employee base is well over 20,000. We have over 2,000 people with PhDs, so we've really become a scientific think tank and hiring lots of people from big pharma and biotech who leave for a variety of reasons. We have about 10,000 clients, 2,000 are biopharma.
We have a lot of locations now from significant number of acquisitions, so about 150 sites in 20 countries. We're proud of the fact that we worked on more than 80% of all the drugs approved over the last three years. I think last year we worked on 100% of all the oncology drugs. We did all the safety work on all the COVID vaccines and therapeutics, we're proud of our role in the drug development ecosystem. Interestingly enough, in our discovery business, we've actually discovered 95 preclinical candidates for our clients that couldn't discover them themselves.
We go off, and we actually find the targets for them, but a third of those are in the clinic, and we have a number one position in many of the things that we do. Last five-year revenue, we had a CAGR of almost 14%, EPS CAGR a little over 16%. Operating income has improved materially. LTM's a little over 21%. Our free we've always been a great free cash flow story. You can see that free cash flow has dramatically improved, except for the current year, where our CapEx has gone up to accommodate our growth rate. We have significant growth in our, particularly our safety assessment, CDMO and our biologics businesses. I think the distinguishing feature of Charles River has been our platform.
It's primarily been the result of 20 years of M&A, about 60 acquisitions, which has totally distinguished ourselves from the competition. We're working across all drug modalities right now. As I said earlier, you know, I think our flexibility and openness to work in a multiplicity of ways has been really helpful. We have a large client base. We have almost no volatility in our business model. We have very low customer concentration. As we saw, we have 10,000 clients working on thousands of molecules. While some drugs, some companies fail, particularly biotech companies, or they're not well managed, or they don't have good compounds, there's hundreds of new biotech companies created by the venture firms every year. We had 470 new biotech companies last year.
There's definitely been an intensified focus on outsourcing for well over a decade. I think COVID was a bit of an instigator of additional outsourcing, given the fact that during COVID, a lot of our clients couldn't get work done by themselves for big pharma, who had to shut some of the facilities. Definitely a lot of our competition were either closed or had a single site or didn't have a plan on how they would move in a crisis. It stimulated additional growth for us. I'm gonna talk later about the importance of M&A and strategic partnerships to our growth rate and to our whole story. We have three segments which cuts across the whole drug discovery and development continuum.
We have our research model business, which was our original business, making small research models, tools to discover new drugs. We have a large and growing discovery and safety assessment business, which is really doing all the work to get drugs into the clinic. We have an increasingly large manufacturing, which is both doing lot release testing and most recently actually manufacturing drugs in the cell therapy field to go into the clinic. This is a larger breakdown. The research model business, the initial business is a little less than 19% of the company. It had very slow growth over some significant period of time, and the growth has begun to accelerate. That business was kind of low to mid-single digit for the longest period of time.
It's now high single digits with high 20s operating margins. The discovery and safety assessment business is now the preponderance of what we do, so it's about 60%. Even at that scale, it's growing at low double-digit rates with operating margins in the mid-20s. I do think that there's operating margin opportunity in pretty much everything we do, particularly the DSA segment. In the manufacturing segment, which is a bit misleading here. The microbial solutions and biologics testing portions are still growing at double-digit rates even though this is 8.6%. We bought a bunch of CDMO assets in the cell and gene therapy space, and as we reported all of 2022, we had a headwind from those acquisitions. It was just tougher integration than we had anticipated, so it slowed our growth rate down.
Those businesses will have a much better 2023. The operating margin profile for those businesses was in the mid-30s, LTMs of a little less than 32%. That's the top and bottom line of our businesses. Just to unpack that further. Our RMS business, we have a number one share position, one out of every two small research models used by any researcher in the world comes from us. We have a slightly less than a 40% market share, about 150 different models. Proximity is really important. We have a live product that has to get to the client in the most pristine state and go off and right on study. We have a large international infrastructure that's worked really well for us.
We've grown a really interesting service business over the last 20 years in research models, which is part of the stimulation of the top line, and actually has been creative to the bottom line. Over the last two years, we bought two cell supply companies, which obviously you're not doing cell therapy research, whether you're an academic or a biotech company that's doing cell therapy work without the cells. We like this portfolio a lot. On the service side, we have two primary businesses. One is our genetically engineered models bi-business where we've either knocked in genes or knocked out genes to, for these animal models to have human-like disease traits.
The genetics has become increasingly more complex, particularly with CRISPR, and we're able to develop really important research tools here. One of our most interesting businesses is this thing we call CRADL, which I always forget what the acronym stands for, but it's an incubator space. We thought it would be only small clients. It's turned out to be small, medium, and large clients, where we have now 28 facilities around the world, staffed with our people, with racks, very sophisticated racks of animals, where we'll either take care of the animals or run some of the study or hopefully at some point run the entire study. We have almost 400,000 feet in that business and did an acquisition in the middle of the year, which is going extremely well.
High growth, high margin business, this CRADL thing. This is really early research. If the drug looks promising, it's likely but not required, but likely the client will stay with us through discovery and through regulated talks. DSA segment, as I said earlier, we've discovered 95 preclinical candidates. We have about a 40% share, so we're by far the industry leader. Our next largest competitor has a 17% share after that. Since we bought much of the second tier, there's not much of a, there's only one competitor in the second tier, and there's not much of a third tier. The space has really congealed rather rapidly. All of our discovery and safety businesses were acquired. We have 30 locations.
That's almost the same number of acquisitions that we made in that space. I would remind you that the preclinical studies are five to 10 times less expensive than clinical studies. Some of the questions we've been getting about funding and what the trajectory is, I think any client that has a promising drug is gonna get through an IND and is gonna do everything they can to get in the clinic. They're not gonna let it languish. We like our discovery business. It's probably the most strategic thing we've done. We wanted to engage with the client as early as possible. We have chemistry, we have in vitro capabilities, so non-animal work. We have a big oncology franchise and a big CNS, central nervous system, franchise, a bunch of laboratory testing, ancillary capabilities.
We have increasingly integrated programs that we're selling to our clients across multiple areas in Charles River. Our safety assessment business is really large, as I just said, and we have a whole host of capabilities. We have the largest collection of veterinary pathologists in the world, probably 150 of them. We do bioanalysis, which is really critical part of the process. We do a lot of specialty talks. Things like immunotox and bone tox and ocular tox, which has a higher margin profile and less competition. This segment has been growing disproportionately fast, very big footprint in big pharma and multiple biotech companies.
I think you all understand that, virtually none of our biotech clients have any safety assessment capability except for a handful of very large ones that you all could name, and even they are not using the facilities as much as they used to. Most of our big pharma clients, not all, but most of our big pharma clients have stopped doing safety assessment as well. Many of them, we do 100% of the work. Most of them, we do a majority of the work. Some still do it internally. Between the two of them, it's about a $11 billion market growing quite nicely. Done some nice acquisitions. I don't know if you can read this, but Distributed Bio, which is on the left, is a small technology deal that we did that we ended up buying the company.
It's large molecule discovery. We were stronger in small molecule. Retrogenix, another company that we bought, looks at on and off-target results. These other three companies were three of our big tox competitors that we bought over the last, I don't know, five or six years. Both the spaces are interesting. Discovery is only 25% outsourced. Some significant part of discovery is obviously done by our clients, so some of that probably will never be outsourced. We're quite confident that the 25% will get to 50 at some point. Safety is probably 60% outsourced. We're quite confident that'll get to 80% or 85% at some point. We still have a significant amount of growth. For biotech, we eliminate the necessity for them to build their own facilities.
For pharma, we eliminate the necessity for them to continue to operate those facilities. Increasingly, our discovery clients are doing safety work with us. Acquisition and availability of animal models to do the work, most recently, large animal models, non-human primates in particular, is a continued critical resource for us. We spend a lot of time increasing the portfolio of countries to work in and companies in those countries to work with. Extraordinarily high demand because these animal models are used for large molecule work, including cell and gene therapy. It has always been and remains a very fluid situation. I think we did a really great job having sufficient number of NHPs in 2021 and 2022.
Obviously, we intend to do everything we can to satisfy the client demand in 2023 as well. We'll provide a greater in-depth update on where we are with all of our supply sources when we give our fourth quarter and 2023 guidance in February. Manufacturing solutions business is a really interesting part of the company. As I said, that 8.6% growth rate is misleading. This is a part of the company that's typically grown forever at at least low double digits. This microbial solutions business has grown at low double digits for 25 years, credibly profitable. That's the business that does quality control and lot release testing required by law of injectable drugs and medical devices.
You have to sample every lot that you manufacture to make sure that your drug or device didn't get contaminated. We have a very sophisticated handheld device with a cartridge that gets utilized and thrown away daily. This is like a razor and razor blade methodology. You can see to the right here, that 70% of the revenue comes from the disposables. Terrific business. Biologics business is the business which is the most competitive. We have really big, really well-financed, very sophisticated competitors. Notwithstanding that fact, we're all doing well. This business is growing dramatically. Operating margins are improving. We've made some significant investments in space. You know, we're testing and characterizing and cell banking large molecule drugs and making sure that they're safe before the drugs go into the clinic. Like this business a lot.
This business has definitely been fueled by cell and gene therapy. Now we made seven acquisitions over the last two years in the cell and gene therapy space. As we reported all of 2022, it was a challenging process. We just bought them fast. The science is really complicated, I think we've done a really great job sort of recapitulating the businesses, the staffing, the regulatory folks. I think we're in a great place now to grow that business, those businesses beginning this year. I think our strong holes in is in cell therapy manufacturing, gene modified cell therapy manufacturing. We have our clients are now all clinical in nature, but several we're in discussions with about them moving into a commercial domain.
We have been inspected by the EMA, which is comparable to the FDA, and passed that inspection with flying colors. We anticipate that that business will contribute materially to both our top and bottom line. Just a little bit more on the microbial business. Even though we have high growth and margins and this wonderful device, only 10% of the volume has converted to this device. We have some wonderful opportunities there. We have a lot of questions about what the demand curve is in cell and gene therapy, both in the manufacturing side and on the testing side. There's over 3,000 cell and gene therapy molecules kind of in the queue. About two-thirds of those need preclinical work.
We're very busy in our, in our biologics sector, anticipate we'll be increasingly busy in our straight up cell and gene therapy businesses which you see at the bottom of the slide, that's Cognate and Vigene. Done some very interesting acquisitions in discovery over the last few years that has allowed us to engage with the clients early and accelerate the work that we do from discovery and helping the clients get work into the clinic. You can see here that when we bought Argenta and BioFocus, it's probably 10 years now, it was a chemistry business with a little biology. It's now a biology business with a little bit of chemistry. We're able to help discover compounds and get them into preclinical development.
When we bought Distributed Bio just, I think a year and a half ago, we now can discover large molecules, mostly antibodies, and get those into preclinical development. With Cognate and Vigene, our cell and gene therapy businesses, we're able to work from a discovery point of view all the way through actually getting the drugs into the clinic. You know, we're only gonna buy things that enhance the portfolio, make us more relevant to the clients, and usually based upon requests from our clients that they'd like to see us do X, Y, or Z because no one does it, or they don't wanna do it anymore, or they're not, they're working with someone who does it really well, but they're too small, and they're concerned about the sustainability.
The cell and gene therapy footprint is really, really interesting. Across the whole portfolio, we do a multiplicity of things. On the research model side, we have a whole very sophisticated immunocompromised mice with no immune system. On the microbial solutions business, we're looking at rapid screening of these molecules. In discovery and safety, we have these combination trials that very few companies can do because very few companies do safety and discovery. On the safety side, specifically, we do a bunch of bioanalytical testing and immunogenicity. We also do bioanalytical testing in the biologics side. We have now these seven businesses as a straight-up cell and gene therapy. I would say that we have two principal competitors in the cell and gene therapy space.
I'd say that we are currently a major competitor on our way to being the principal player in cell therapy manufacturing. We're excited about the space. We're excited about our footprint. We're excited about the technology. We're excited about working across our whole portfolio because even competitors who are bigger companies, and let's say are bigger CDMOs, and we have those, there's only one entry point into working with them, and that's when they're ready to do manufacturing, as opposed to starting with us literally when the target is found or the drug is developed and working with us through the whole development process. We like starting early with the client and staying with them through the clinic. We spent a lot of time over the last three years on digitizing Charles River.
We're way too manual right now, I think because we're way too manual or have been too manual, it slows us down. I think there are unnecessary costs. Our clients are only interested in speed. They're interested in connectivity. We promised our clients that we can take a year out of the drug development process. We're in the process of doing that. We've also told them we'll take the white space out. You know, the space with it we've always done things, we and our clients, a certain way. No one really remembers why. It doesn't add any value. We need to stop doing it. If they're making a decision on a two-page report, why are we sending them a 200-page report? We're changing all of those things.
The model is for a client who needs to do a toxicology study to get online, say, "I know Charles River does toxicology," get online, book a slot, get a price, initiate the study, get the data daily, and only talk to us when they have something equivocal or they have a question on the science, as opposed to be talking to a human being on every step. To really these e-commerce solutions are really speeding up the business across our whole portfolio.
We're starting to spend a bunch of time now on taking our data, with an effort to try to design better preclinical trials with better outcomes with our clients, and at some point, linking our study designs with the clinical CROs so that we're looking at the same biomarkers as they are, with the, obviously, the ultimate goal of helping the clients get more drugs to market, period. As opposed to just get more drugs, the same number of drugs to market faster. We'll be pleased and proud if we can just help them get the drugs to market faster. If we can help get several billion-dollar drugs to market a year earlier, that obviously is quite meaningful to them. We, you know, we have this fabulously diverse client base, so very little volatility.
The largest clients, only about 3% of our revenue. The top 25 are about 30%. As I said earlier, 2,000 biopharma clients. Very heavy biotech and big pharma. You can see here that year to date, we've added 485 new biotech companies. While there is churn, I think particularly in the biotech sector, we don't feel it. We have about a $20 billion addressable market, kind of growing at little greater than 10%. You can see the various specific markets. At a $4-ish billion run rate, that's a really long runway for us to continue to grow this franchise for sure, organically, and I suspect increasingly or consistently utilizing M&A. This is a really important slide here.
We've done about 60 acquisitions since we took this company private at the end of 99. It remains our principal use of our capital. I think we have built a very unique, very interesting company that's tough to compete with and one that's really respected and used widely by our client base. It's a simple fact that many, many drugs just simply don't get to market if we didn't exist. We spent about four and a half billion dollars in the last on the last 25 acquisitions in the last 10 years. I think our integration results haven't been perfect, but they've been really good.
We have a full-time integration team that works on every deal, does all the valuation metrics and all the due diligence, and I think we really understand the ethos of the targets and understand their cultures and have done a good job of putting them together. We will continue to buy companies. I think our balance sheet is strong. I don't think we have a lot of huge gaps, but we have some areas that we'd like to be wider and deeper, some areas with like geographic reach to extend and, we have multiple conversations going on right now. We wanna stay quasi cutting edge from a scientific point of view. I'm not sure we need to be cutting edge, but close. We have about 20 deals right now, where we've committed over $100 million.
Two of them we bought that I talked about earlier. It's everything from AI to 3D modeling, to next generation sequencing, to more large molecule and antibody stuff. And we look at it as R&D, and I think some of those technologies won't work. We either provide equity or debt financing. We're the sales and marketing conduit for these companies, which is an amazing way to do due diligence. We'll probably end up buying a third of them, probably end up working with another third, we'll probably end up writing off the remaining third. One source of acquisitions, particularly for our discovery business, will be the strategic deals. Our venture capital relationships have been magic. This is now about 15 years ago, we made our first investment as an LP.
I went myself and met with these folks and said, "I wanna tell you all the things that we're doing that could help your portfolio companies, and we'll give you pricing as if you're a larger company." We have I think seven or eight of these deals where we're LPs. We also get the returns on the funds, which is not the reason we did it. We have probably the same number of venture firms that wanna work with us strategically but don't need or want our money. We have another cadre of venture firms that don't need or want our money, that don't work with us strategically. If you look at venture firm's portfolio companies in the aggregate, it's about 10% of our revenue.
It's going to be a really big number, and we're getting terrific returns on those VC investments as well. Spending a lot of time on a whole bunch of corporate citizenship issues from DE&I at the board level, at the management level. We have these great employee resource groups that I think have been fundamentally positive and powerful for the company. We spend a lot of time supporting charitable organizations in the places that we live and work. Spend a lot of time working on sustainability and reducing our greenhouse gas emissions, and we'll stay maniacally focused on all of these things. We're in a period now where we've never seen the demand this strong. The portfolio is really incredibly unique, and we will continue to add to it.
We're gonna continue to drive efficiency from best practices, but also through digitization, as I said earlier, take a year out. We're gonna focus things on e-commerce and AI. We'll, we will add to the portfolio through M&A. We want, we want Charles River to be a place where great scientists and people who actually wanna make a fundamental difference in the world will not only come, but will come and stay. If we have time left, I will pause and answer your questions.
Thanks for that overview, Jim. Now we'll shift to the Q&A portion. If you have any questions, please feel free to raise your hand or submit them via the webcast. Jim, just to start, wanted to dig into the NHP situation. So, you know, you previously stated that more than 50% of your NHP supply comes from Cambodia, and there's been estimates out there, around the percentage of DSA revenue tied to NHPs, as high as 50%. Can you maybe just walk through what your NHP revenue exposure is, and by how much mitigation measures around supplier diversification, could limit the impact, of a complete Cambodian supply shutdown, if that were to occur?
Yeah. I'm not, I'm not gonna unpack it. Can you hear me? I'm not gonna unpack it, that finely. It's a fluid situation. It's really critical model for all large molecule work, including cell and gene therapy. We have a multiplicity of supply arrangements with several countries and several players within those countries. We had, I think we did a really good job ensuring a sufficient supply in 2021 and 2022. We intend to do everything we can to have a sufficient supply in 2023. We'll go really deep on the details. I'm still not sure we'll go that deep, but we'll go really deep on the details when we give our guidance in February.
Maybe turning to the CDMO, just can you touch on what sort of traction you've made on the retooling plan there? Can we expect this business to normalize at some point in 2023?
Yeah.
Just, yeah, how the order book has trended there, and would you expect adequate supply-demand?
Yeah.
After the retooling's done?
I mean, you know, our strategy is to, you know, we don't have any of our own drugs. We don't have any parts and pieces of anyone's drugs, but we wanna support all modalities. We wanna work with everybody who will work with us across multiple modalities. There's no question that cell and gene therapy, if it isn't already, is gonna be a big deal in terms of treating and potentially curing a lot of diseases. As I showed in one of the slides, before we bought these straight up assets, we were doing a fair amount of work in cell and gene therapy across our legacy portfolio, I would say. We're really pleased with the assets we bought.
We bought them fast, and by that I mean, you know, deals have like a heartbeat, and when they're available, if you want them, you sometimes have to move on them. And not making any excuses, but I do think that COVID complicated our ability to kinda get as close to some of these enterprises as we typically would have. A little bit of that, but a lot of new science, a new area for us, learning as we go. I think the regulators are learning as they go, clients are learning as they go, and even our competitors are. The integration is definitely took longer than we had anticipated. We have essentially new management teams, really strong regulatory and sales folks we've added to all of the facilities, and the order book is actually increasing very nicely.
We have this very interesting cadre of clients, for whom we are making clinical trial lots of cell therapy drugs, several of whom anticipate that their drugs will go commercial in the not too distant future. I can't tell you when that will be. As I said earlier, we already have been inspected by the EMA. You know, directionally, we think there will be high growth in that business. Two other parts of that business are viral vector manufacturing and plasmid DNA manufacturing, partially for cell therapy, but principally for gene therapy work. We like the assets. They will have a much better year in 2023. I understand those are easy comms. The demand is great, and as I said, during my prepared remarks, I do think we have an opportunity to be the principal player in cell therapy.
Can you provide an update on the biotech funding environment within your business, how those mid customers are trending right now? You know, 2022 is dominated by headlines around biotech firm restructuring and portfolio rationalization. Charles River has continued to deliver strong DSA growth and backlog. Just curious if you've seen any shift in tenor in those conversations with those customers.
Yeah. The whole biotech funding conversation is a sort of maniacal over-focus by our shareholder base. For a while, the better it got, the more nervous folks got. You know, IPOs ground to a halt, and I think everybody sort of flipped out. You know, the reality is 2022 was really good year in biotech funding. It was comparable to 2018 and 2019. 2020 was a particularly good year, and 2021 was an insanely good year. The third quarter of 2022 was the fifth-best quarter in the history of biotech. It's a bit of a red herring, the whole conversation, as far as I'm concerned. You know, we had a really strong 2021. We haven't finished reporting on 2022, but the three quarters we reported on were quite strong. Our guidance for the year was as well.
We haven't seen any impact. Conversely, the demand curve has elongated the best it ever was. We reported all of 2022 that we were booked well into 2023 and into 2024 at escalating price points. We've never seen that before. We feel our client base, both at the VC level, at the pharma level, and at the biotech level, with the exception of a very small percentage, are well-funded. Look, if you're a biotech company that has a promising compound for an unmet medical need, and you're either running out of cash because you miscalculated or you mismanaged, a pharma's gonna ride in on a white horse and fund you for sure. No decent drug is gonna languish or go belly up.
I think companies fail because, I don't know, the drugs didn't work. They ran out of money. It was another me-too drug. As I showed in one of the slides, we added 470 new clients. I think that eliminates the churn. We, you know, without getting into 2023, because we haven't given guidance, we don't anticipate the demand curve should change. If anything, I think people could feel better about the capital markets. I do think it's an overreaction. As I said earlier, if you have a drug that you need to get through preclinical so the drug can get into the clinic, you'll do everything you can to make sure that happens.
Maybe one more question. Just going back to the slide deck, you outlined the $20 billion addressable market growing 10% over the long term. How do you see Charles River's long-term growth compared to that? You know, the prior long-term guide had been low double-digit top line growth. Just curious if you have any update to that, and if you're still expecting 22.5% operating margins by 2024.
Will give an update on those metrics the next time we have an investor conference. You know, for now, we have to leave those numbers as they are, 'cause those are out there in the public domain. We feel really good about our growth rate, what they've been recently and what the outlook is for the future. I think we'll wait. We wanna wait until we report on this year, how did the year finish, what does 2023 look like, and then we'll sort of riff off of 2023 in terms of giving longer term guidance. You know, we gave two year guidance at one point, we gave five year guidance at another point. We most recently gave three and a half year guidance. Probably we'll do something sort of between two and five again, but you'll have to wait for that.
Got it. maybe just going back to your point around big pharma-, kind of coming in on their white horse and saving some of those drugs from biotech. Have you seen that already in the market? Just more curious on big pharma trends within assay testing. You noted that those customers are doing less in-house testing and choosing to outsource to you. Why is that occurring?
Yeah, I mean, you see it daily. I mean, 50%-70% of all the drugs that the pharmaceutical industry has are externally resourced. So they're constantly looking for and either buying drugs, buying companies, buying U.S. rights, buying foreign rights. So I think that will continue. We found that our pharmaceutical demand has been particularly strong over most of 2022. The majority of our clients have continued to do less in-house and rely more on outsourcing. You know, our scientific capabilities have recently eclipsed the work that they were able to do internally.
Got it. Looks like we have 30 seconds left. Anybody have any questions from the crowd? No. All right. I guess we can leave it at that, Jim. Thank you.
Thanks.
Thanks to everybody for coming, and enjoy the rest of the conference.