#16 - A Discussion on the Future of Knee Replacements

My name is Sam, and I will be your humble guide through today's episode. Today, we're talking about knee replacements. This is The Tech Optimist.

We are endeavoring to develop an implant for more effectively treating trauma and arthritic cartilage loss in younger patients. In fact, the best way to reach this particular patient population will be with a truly off-the-shelf device. I think that's one of the biggest headaches we've heard from surgeons.

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All right, so I'm really pleased to speak today with Ben Holmes. He's the CEO of NanoCon. Which is doing something that I think a lot of us can relate to, but I'll let Ben explain it. Tell us about your company and the problems it's trying to address.

Yeah, absolutely. And, it's really great to be here today, Mike. I appreciate it. NanoCon is an early-stage medical device company which is developing an implant for treating cartilage damage and loss in joints. We're specifically focusing on the knee first because that is the largest clinical need and also the indication which is growing at the fastest rate. Actually, the number of total knee replacements that are done annually is growing at an alarming rate. And several years ago, knee replacement actually surpassed hip replacement as the most widely done elective surgery. So, it's an enormous problem. And as I'm sure many of your listeners will know, The knee replacement is costly. It's invasive, takes up to a year to recover from, and it's really only a solution for older patients that are not nearly as active as, you know, a younger patient population might be. So, when we say active, I mean, we're really focusing on a patient cohort that does have substantial damage to their cartilage, whether it's from trauma, or from developing arthritis, but are really just too young for a knee replacement to make sense, both because knee replacement has a limited lifespan and also because the expectation for quality of life improvement is much, much higher. So we are endeavoring to develop an implant for more effectively treating trauma and arthritic cartilage loss in younger patients with an implant that really is designed to do a couple things. One, it's designed to really just replace the damaged area. So instead of pulling out the whole joint and replacing it with metal and plastic, you can use our implant to effectively just fill in the areas where the cartilage has degenerated. And especially in joints like the knee, that cartilage degeneration tends to follow, you know, the mechanics of the joint. So it ends up presenting as, you know, what's called a focal lesion, basically like a pothole in the road. So we've got something that can fill the pothole, but also the implant itself works with cell populations in the body to actually regenerate new tissue. So, we've shown in a number of studies now that you actually get integration with the bone underneath as well as the cartilage layer. So, that's really critical for actually getting good long-term results because right now, the stopgap treatments that most of these patients are receiving, that's part of the reason why they fail. The cartilage that grows is not the proper type of cartilage, so it has a kind of a weak mechanical character, I guess, is the right way to describe it. It's almost kind of like Jell-O or it's kind of like a goop. It's pretty nasty stuff. That's how people are being treated today, but that bone continues to degenerate. So, Rehabbing the bone as well as the cartilage is really key. But then also the implant itself can bear weight immediately. And so that really what that means is that typical in today's treatments, patients will get surgery and then they can't put any weight on their joint at all. So they're walking around in crutches, in a brace for usually like a minimum of 2 months. Sometimes it could be up to 3 months before they can even start rehab. Whereas with an implant like ours that's designed to be mechanically stable, they actually can do rehab right away. So we believe that the experience for patients will be not just one of longevity, but also one that is much faster, maybe a period of 4 to 6 months maximum to get to a place of being fully healed. As opposed to, like I said, sort of up to a year. which is required now for some of these treatments, and also certainly for knee replacement.

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This sounds like a plant, but I was literally out, um, with friends, uh, a couple of nights ago, and one of my friends who I hadn't seen in a while, uh, was a runner, and I was asking him about his running and You know, no, I've had to give up running because, because of my knee. And it's like, you know, I don't want to have a knee replacement yet. So I've moved to kind of an exercise bike and, and these non-impact kind of things. And it's like, it was very disappointing to him. And I think really, he was really looking for alternatives. And, it sounds like there's a huge cohort of people that kind of fall into that category. So, this is a big problem for sure.

Yeah, yeah, absolutely. And honestly, I get probably dozens of emails a month of people like your friend that you just described that basically tell exactly that story. I'm whatever age, I've been a lifelong I'm a runner or a skier or I like to play pickup basketball, whatever it is, and my joints have gotten really bad and knee replacement will eliminate the pain, but it's going to basically mean I still have to give up everything anyway. So, I really want alternatives. So, definitely, that's something that continues to drive us is that the patients are there and the patients are very much in need of better solutions. So, that's really been motivating us for a long time. Where are you in your journey? I mean, this is an

This is an early-stage company. I mean, you're at the beginning of your journey. Could you give our listeners a little bit of context of the companies and where are you and where did it come from and kind of where are you in the entrepreneurial journey, Ben?

Yeah. So, I'll sort of start where we are today and then work backwards. So, we are about to conduct our first human clinical trial. So, this is a small safety study. We're talking about enrolling 10 patients. We've already got one of the clinical sites lined up, but we are looking to recruit a second clinical site. But basically, this will be the first use of NanoCon's implant in human beings. So, that's very, very exciting. We're expecting to be conducting the first surgery in the fall. So, assuming that we kind of move through all the gates at an appropriate pace, we could be doing the first surgery maybe in September. But, prior to that, it's really been, and as it is with any invasive implant, there's a lot of preclinical testing you have to do. So, we most recently did a study in horses to show the efficacy and the ability of the implant to do the things that we say it can do and got really phenomenal results there. Okay. Prior to that, we also had done a goat study. So, that was sort of the first demonstration of the implant doing anything at all. And then, before that, it was really a lot of much more basic R&D. When we founded the company, we'd gotten a small research grant to do a rodent study. So, that's the first time that the implant had been used in anything that was living. And also, we were looking at different candidate materials as well. So, we actually had a couple different technologies that we were looking at. Going all the way back in time, my co-founder and I originally met and started working on this technology in the tissue engineering lab at George Washington University. So, we were both PhD students working broadly on biomaterials and advanced fabrication to try to get cells to grow, primarily working with stem cells and also MSCs, which are a pluripotent cell that's found in bone. Yeah. And responsible for a lot of skeletal tissue remodeling. And, we also had a really keen interest in 3D printing. So, I guess I didn't really explain what the technology is yet. So, we have a nanomaterial that essentially mimics the collagen structure of cartilage. So, it's a fully synthetic polymer material but has this collagen-like structure. So, cells like to attach to it, they like to grow on it, and they kind of grow in an elongated fashion. like cells that reside in native cartilage. And then, we also 3D print it into this larger, more well-connected 3-dimensional pore structure. So, to be super clear, we're not doing 3D printing for patient-specific devices. That's on the roadmap for the future, but that's not what we're doing today. In fact, the best way to reach this particular patient population will be with a truly off-the-shelf device. I think that's one of the biggest headaches we've heard from surgeons. With the existing kind of tissue grafting and cell therapy techniques is they're highly bespoke. They're essentially crafted on a case-by-case basis with some exceptions. And, that's just a huge bottleneck. So, the dream is really to have something that's a fully off-the-shelf product, but 3D printing allows us to take this very bioactive material that the body likes to grow into And make a truly 3-dimensional structure in a very efficient and cost-effective way. So really, it's a manufacturing strategy to have something that has the complexity that's required to work with biology, but be something that's very easy to scale and turn into a distributable product, essentially. So 3D printing has become very manufacturing-friendly, all things considered, and we can turn out relatively high volumes of these implants when necessary on the market. So, that's also another really important piece of what we're doing, that this is not another attempt to 3D print live material or live cells suspended in a gel. I mean, this really is kind of a high-volume, high-throughput approach and a technology that could really be very easy to deploy in a clinical setting.

Yeah, through the existing systems, in essence. Is there any work to be done in kind of the microenvironment there to kind of get the scaffolding to grow better or well beyond the geometry and material choices?

Yeah, I guess if I understand your question correctly, are you talking about sort of like adding coatings or Yeah, I just wonder, how do you facilitate

the growth of cartilage in there? Or does it just happen naturally or is there anything you can do to accelerate it to kind of fertilize the area, if you will?

Yeah, I got you. So, it definitely doesn't happen naturally. And I mean, that's the big challenge is that cartilage, many tissues have limited ability to repair, but cartilage has no ability to repair. Yeah. And, the primary reason for that is because there's no blood supply in cartilage. It has no blood vessels. It's essentially an embryonic tissue. So, when we all start out as a fetus in the womb, the skeletal system first develops as a network of connective tissue and cartilage. And

then,

that cartilage kind of starts to calcify from the inside out. And so, the cartilage surface of joints is really what's left over from that embryonic development process. So, that's part of why it's so challenging. But, the microenvironment of our scaffold of what's 3D printed is designed to basically draw cells up from the bone. Love it. And, there's other companies that have started to explore this for other types of skeletal tissue. It's been really widely explored for tendon And, there's a couple companies that are sort of trying to leverage the same effect for reattaching the rotator cuff to the bone and stuff like that, like shoulder trauma, other types of extremity trauma. So, it's a similar idea. And so, really what our implant is designed to do is we believe there is some migration of chondrocytes out from the cartilage in, but it's primarily MSCs coming up from the bone. Got

it.

So, the most important part of that is you have to prep the defect in order to make the bone bleed, which again, this is super common. I mean, the most common surgical technique is still something called microfracture where you're literally just poking holes in the bone to make it bleed. And, people kind of have returned to activity for a couple years. It's quick and easy to do but doesn't really have good long-term results, right? So, this scaffold is designed to support cells coming up from that blood. And, we've essentially designed a surgical technique in an introducer set which literally allows the surgeon to just kind of drill through the damaged tissue, drill enough into the bone that you get some bleeding, and then the implant is designed to basically slot into that hole that the surgeon drilled prior. So, the bleeding that comes from drilling that hole essentially allows the access to to active cell populations that then come up into the implant and repopulate it and then grow into cartilage and bone. That's super cool.

And, you were seeing that in the horses? Yeah,

yeah, yeah. We saw that in the horses. We saw that in the goats previously.

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You know, is this— does this buy you another 5 years, 10 years? What are you hoping? Are you just gonna have to wait and see?

Yeah, so I mean, in this, in this space, there's a couple important primary endpoints. I mean, our, our path through the FDA past this initial study, which is just a 1-year safety study, will be to do a large, you know, larger multi-arm clinical trial. That's going to require a 2-year follow-up to get FDA approval. And, that's the first critical time point because that's when microfracture fails typically. I think in 85% of patients, microfracture fails within 2 years. So, if you can show superior to microfracture, you've already solved an enormous segment of the problem, which is just what do you do with someone who's coming in for the first time. Beyond that though, things like cadaveric grafting and the cell therapy products, have been shown to typically fail within 5 years. And so, that's the other important time point. And, there's a little bit more nuance to that where it's sort of like, okay, there's also this whole cohort of people that kind of includes some of the microfracture patients. It also includes other types of non-implantation procedures that are designed to try to smooth out or restore some function of the joint. And then, also includes the therapeutics, the tissue grafting, all that. And, that stuff kind of combined typically fails within 5 years. And, that's when people progress to needing a knee replacement. So again, there's some nuance to that. You can kind of argue that maybe those are because they're older patients anyway or what have you, but the point is the 5-year time point is the next most important one. So, our initial goal here is very measured, right? It's just to show we're better than microfracture. And so, that would allow us to get an indication from the FDA.

That's

a win. Yeah. And, go on the market. And, that's a big win because that's That's hundreds of thousands of patients. I mean, if you add up all of the cell therapies and all of the tissue grafting, I mean, there's, I think, almost 800,000 knee arthroscopies done every year. And roughly 30,000 of those are all of the therapeutics and the tissue grafting things combined. Everything else is microfracture or other arthroscopic surgical techniques. So, that's already a big segment of the market. But then, The ability to open up that kind of longer-term benefit comes once we're on the market. So, other companies in the cell therapeutic space have done this where once they're able to enter the market, they then continue to attract patients. And then, once they've got an additional couple hundred patients that they've been able to follow for 5 years, then they can start to market different claims. So, that's kind of a longer-term play.

That's the playbook, yeah.

Yeah.

What's the ask for our community? How can a listener or a friend of a listener or a friend of a friend of a listener help?

Yeah. I mean, right now, we're really just trying to build up our clinical network, right? So, like I said, we're well set up to do this first small study, but we'll be looking to probably start recruiting clinical sites for the pivotal trial pretty early next year. So, right now, we're just, again, trying to build a network of potential clinical sites for a pivotal trial that could be interested.

Yeah. And, what's a great site look like to you? What's the generic? What are you looking for?

Yeah. I mean, definitely somebody in the sports medicine vertical. So, this would not be someone who just does a bunch of knee replacements. This would be someone who is an arthroscopic specialist who is seeing this kind of I'll say everything from a 20-year-old athlete who fell on the soccer field and ripped a big piece of their cartilage off all the way up to someone who's seeing, again, kind of like your friend, people who maybe could get an early knee replacement but are looking for alternatives. So, surgeons that are kind of seeing that range of patients. Yeah. We're also trying to include some surgeons who maybe work with pro athletes. Because we also believe because of the ability for really fast rehab and really fast return to sport, we think this could be something that could really show benefit in the professional athlete community. So, again, that wouldn't be the whole focus, but the ability to include some of those types of patients could be really phenomenal. So, also, anyone who treats pro athletes I think would be a good addition to the clinical cohort.

Oh, we definitely have all of that. So again, we'll in the show notes put places where people can reach out with interest or connections there to be helpful.

Perfect, perfect.

Well, again, it's been really nice to meet you. Fascinating. Again, I think I've got maybe 5 years myself before I'm going to probably be a candidate. I'm just starting to get a little clicking sound in the right knee. So, it's like I think it's a matter of time for us ex-athletes. to need this kind of stuff. So, it was really nice meeting you and continued good luck on your journey. Just love people solving hard problems and taking the journey to make the world a little better. So, thanks for your work, Ben, and keep it up.

Yeah, my pleasure. And, thanks for taking the time today. It's great to get the story out there and let people know what we're up to. So, I appreciate it. Thank you.

Excellent. All right, have a good one.

Nice to meet you, Ben. Nice to meet you too. Yeah.

Yeah.

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