Episode #16: A Discussion on the Future of Knee Replacements

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  Sam (Narrator):
  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.

  Ben Holmes:
  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.

  Sam (Narrator):
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  As a reminder, the Tech Optimist podcast is for informational purposes only. It is not personalized advice, and it’s not an offer to buy or sell securities. For additional important details, please see the text description accompanying this episode.

  Okay, let’s dive right into the episode. Mike Collins, CEO here at Alumni Ventures, sits down with Ben Holmes, the CEO behind medical device company NanoCon. I, Sam, being a podcast producer, know literally nothing about the medical world and medical technology, engineering, and innovation, but Ben does a really good job of explaining and articulating what his company’s technology is and what their mission is within the medical space. He explains how their knee replacement implant can revolutionize this type of injury recovery for surgeons and patients struggling with this debilitating issue that affects hundreds of thousands of people across the globe. Learn more about NanoCon, Ben, their implant, and what’s on the horizon for them within the medical technology space.

  Take it away, Mike. Let’s get into it.

  Mike:
  All right, so I am 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.

  Ben Holmes:
  Yeah, absolutely. And it’s really great to be here today, Mike. I appreciate it. NanoCon is an early-stage medical device company 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 growing at the fastest rate.

  Actually, the number of total knee replacements done annually is growing at an alarming rate. Several years ago, knee replacement 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 know, knee replacement is costly, invasive, takes up to a year to recover from, and is really only a solution for older patients that are not nearly as active as a younger patient population might be.

  When we say active, we are focusing on a patient cohort with substantial cartilage damage, whether from trauma or developing arthritis, but who are too young for a knee replacement to make sense. This is both because knee replacement has a limited lifespan and because the expectation for quality of life improvement is much higher.

  We are developing an implant for more effectively treating trauma and arthritic cartilage loss in younger patients with an implant designed to do a couple of things. One, it’s designed to replace only the damaged area. Instead of pulling out the whole joint and replacing it with metal and plastic, you can use our implant to fill in the areas where cartilage has degenerated.

  Especially in joints like the knee, cartilage degeneration tends to follow the mechanics of the joint and presents as what’s called a focal lesion—basically like a pothole in the road. We’ve got something that can fill the pothole. But the implant itself also works with cell populations in the body to regenerate new tissue.

  We’ve shown in a number of studies that you actually get integration with the bone underneath as well as the cartilage layer. That’s critical for good, long-term results because right now the stopgap treatments most patients receive fail. The cartilage that grows is not the proper type, has weak mechanical character—it’s almost like Jello or goop. It’s nasty stuff, but that’s how people are treated today. The bone continues to degenerate, so rehabbing both bone and cartilage is key.

  Also, the implant itself can bear weight immediately. Typically, with today’s treatments, patients have surgery and can’t put weight on their joint at all. They walk around on crutches, in a brace, usually for a minimum of two months—sometimes up to three—before starting rehab. With an implant like ours, designed to be mechanically stable, they can rehab right away.

  We believe the experience for patients will not just offer longevity but also a much faster recovery—maybe four to six months to be fully healed compared to up to a year required now for some treatments and certainly for knee replacement.

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  Mike:
  This sounds like a plant, but I was literally out with friends a couple of nights ago, and one of my friends who I hadn’t seen in a while was a runner. I asked him about his running and he said, “No, I’ve had to give up running because of my knee. I don’t want to have a knee replacement yet, so I’ve moved to an exercise bike and other non-impact activities.”

  It was very disappointing to him, and I think he was really looking for alternatives. It sounds like there is a huge cohort of people who fall into that category. This is a big problem for sure.

  Ben Holmes:
  Yeah, absolutely. And honestly, I get dozens of emails a month from people like your friend who tell exactly that story. “I’m whatever age, I’ve been a lifelong runner or skier, I like to play pickup basketball, whatever it is. My joints are in bad shape. Knee replacement will eliminate the pain but basically means I still have to give up everything. I really want alternatives.”

  That continues to drive us. The patients are there, and they are very much in need of better solutions. That’s been motivating us the whole time.

  Mike:
  Where are you in your journey? I mean, this is an early-stage company, you’re at the beginning of your journey. Could you give our listeners a little bit of context about the company, where you are, where it came from, and where you are in the entrepreneurial journey, Ben?

  Ben Holmes:
  Yeah, so I’ll start where we are today and then work backwards. We are about to conduct our first human clinical trial. This is a small safety study, enrolling 10 patients. We’ve already got one of the clinical sites lined up, but we are looking to recruit a second clinical site. This will be the first use of NanoCon’s implant in human beings, which is very exciting. We’re expecting to conduct the first surgery in the fall. Assuming we move through all the gates at an appropriate pace, we could be doing the first surgery in September.

  Prior to that, as with any invasive implant, there’s a lot of preclinical testing. Most recently, we did a study in horses to show the efficacy and ability of the implant to do what we claim it can, and we got phenomenal results. Prior to that, we did a goat study, which was the first demonstration of the implant doing anything at all. Before that, it was much more basic R&D. When we founded the company, we got a small research grant to do a rodent study. That was the first time the implant was used in a living subject. At that stage, we were also looking at different candidate materials—we had a couple of different technologies we were exploring.

  Going further back, my co-founder and I originally met and started working on this technology in the tissue engineering lab at George Washington University. We were both PhD students working broadly on biomaterials and advanced fabrication to get cells to grow, primarily working with stem cells and also MSCs, which are a pluripotent cell found in bone responsible for much of skeletal tissue remodeling.

  We also had a keen interest in 3D printing. I guess I haven’t explained the technology yet. We have a nanomaterial that essentially mimics the collagen structure of cartilage. It’s a fully synthetic polymer material but has this collagen-like structure, so cells like to attach to it, grow on it, and grow in an elongated fashion like cells in native cartilage. We 3D print it into a larger, well-connected, three-dimensional pore structure.

  To be clear, we are not doing 3D printing for patient-specific devices—that’s on the future roadmap. In fact, the best way to reach this patient population will be with a truly off-the-shelf device. One of the biggest headaches we’ve heard from surgeons with existing tissue grafting and cell therapy techniques is that they’re highly bespoke, essentially crafted case by case with some exceptions, creating a huge bottleneck.

  The dream is to have a fully off-the-shelf product. 3D printing allows us to take this bioactive material that the body likes to grow into and make a truly three-dimensional structure efficiently and cost-effectively. It’s a manufacturing strategy that provides the complexity required to work with biology while being easy to scale into a distributable product.

  3D printing has become manufacturing-friendly, and we can produce relatively high volumes of these implants once we’re on the market. This is not another attempt to 3D print live material or cells suspended in a gel. It’s a high-volume, high-throughput approach—a technology that will be very easy to deploy in a clinical setting.

  Mike:
  Through the existing systems, in essence.

  Ben Holmes:
  Yeah.

  Mike:
  Is there any work to be done in the microenvironment to get the scaffolding to grow better, beyond geometry and material choices?

  Ben Holmes:
  Yeah. If I understand your question correctly, are you talking about adding coatings or other biologics?

  Mike:
  Yeah. How do you facilitate the growth of cartilage in there? Does it just happen naturally, or is there anything you can do to accelerate it—to fertilize the area, if you will?

  Ben Holmes:
  Yeah, I gotcha. It definitely doesn’t happen naturally—that’s the big challenge. Many tissues have limited repair ability, but cartilage has no ability to repair. The primary reason is that there’s no blood supply; cartilage has no blood vessels. It’s essentially an embryonic tissue. When we start as a fetus in the womb, the skeletal system first develops as connective tissue and cartilage, which then calcifies from the inside out. The cartilage surface of joints is what’s left from that embryonic process. That’s why it’s so challenging.

  The microenvironment of our 3D-printed scaffold is designed to draw cells up from the bone. Other companies have explored this for skeletal tissue, widely used for tendon reattachment. A couple of companies are trying to leverage the same effect for rotator cuff reattachment and shoulder trauma—similar extremity trauma.

  It’s a similar idea. Our implant is designed to encourage some migration of cells from cartilage, but primarily MSCs come up from the bone.

  Mike:
  Got it.

  Ben Holmes:
  The most important part is prepping the defect to make the bone bleed. This is super common—the most common surgical technique is microfracture, where you poke holes in the bone to make it bleed. People can return to activity for a couple of years. It’s quick and easy but doesn’t have good long-term results.

  Our scaffold is designed to support cells coming up from that blood. We’ve designed a surgical technique and introducer set that allows a surgeon to drill through the damaged tissue, into the bone to create bleeding. The implant slots into that hole, and the bleeding allows access to active cell populations that repopulate the implant, growing into cartilage and bone.

  Mike:
  You were seeing that in the horses.

  Ben Holmes:
  Yeah. We saw that in the horses and in the goats previously.

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  Mike:
  Does this buy you another five years, ten years? What are you hoping for, or do you just have to wait and see?

  Ben Holmes:
  Yeah, in this space, there are a couple of primary endpoints. Our FDA path, after this initial one-year safety study, is to do a larger, multi-arm clinical trial requiring a two-year follow-up for approval. That’s the first critical time point because microfracture typically fails in 85% of patients within two years. If we can show superiority to microfracture, we’ve already solved an enormous part of the problem—what do you do with someone coming in for the first time?

  Beyond that, cadaveric grafting and cell therapy products typically fail within five years—that’s the next important time point. There’s nuance: some failures are because patients are older anyway. But generally, five years is when many progress to needing a knee replacement.

  So our initial goal is measured—just to show we’re better than microfracture. That would allow us to get an FDA indication.

  Mike:
  That’s a win.

  Ben Holmes:
  Yeah. And go on the market. That’s a big win because that’s hundreds of thousands of patients. If you add up all the cell therapies and tissue grafting, there are almost 800,000 knee arthroscopies done every year, and roughly 30,000 of those are therapeutics and tissue grafting combined. Everything else is microfracture or other arthroscopic surgical techniques. So that’s already a big segment of the market.

  The ability to open up that longer-term benefit comes once they’re on the market. Other companies in the cell therapeutic space have done this—once they enter the market, they continue to attract patients. Once they’ve treated an additional couple hundred patients and followed them for five years, they can start marketing different claims. That’s a longer-term goal.

  Mike:
  That’s the playbook. Yeah.

  Ben Holmes:
  Yeah.

  Mike:
  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?

  Ben Holmes:
  Right now, we’re trying to build up our clinical network. Like I said, we’re well set up to do this first small study, but we’ll probably start recruiting clinical sites for the pivotal trial early next year. So right now, we’re building a network of potential clinical sites for that trial.

  Mike:
  And what’s a great site look like to you? What’s the generic profile you’re looking for?

  Ben Holmes:
  Definitely someone in the sports medicine vertical. This isn’t someone who just does a lot of knee replacements. We’re looking for arthroscopic specialists seeing everything from a 20-year-old athlete who tore cartilage on a soccer field to someone like your friend—patients who could get an early knee replacement but are looking for alternatives.

  We’re also trying to include surgeons who work with professional athletes because we believe the ability for really fast rehab and return to sport could show a big benefit in the pro athlete community. That wouldn’t be the entire focus, but including some of those patients could be phenomenal. So, anyone treating pro athletes would be a good addition to the clinical cohorts.

  Mike:
  We definitely have all of that. In the show notes, we’ll include places where people can reach out with interest or connections to help.

  Ben Holmes:
  Perfect. Perfect.

  Mike:
  Well, again, it’s been really nice to meet you. Fascinating. I think I’ve got maybe five years myself before I’m a candidate. I’m starting to get a clicking sound in my right knee—it’s just a matter of time for us ex-athletes to need this kind of stuff.

  It was really nice meeting you, and continued good luck on your journey. I love seeing people solve hard problems and take the journey to make the world a little better. Thanks for your work, Ben, and keep it up.

  Ben Holmes:
  My pleasure. Thanks for taking the time today. It’s great to get the story out and let people know what we’re up to, so I appreciate it. Thank you.

  Mike:
  Excellent. All right. Have a good one.

  Ben Holmes:
  Perfect.

  Mike:
  Nice to meet you, Ben.

  Ben Holmes:
  Nice to meet you too.

  Mike:
  Yeah.

  Ben Holmes:
  Yeah.

  Mike:
  Bye.

  Sam (Narrator):
  Thanks again for tuning into The Tech Optimist. If you enjoyed this episode, we’d really appreciate it if you’d give us a rating on whichever podcast app you’re using. Remember to subscribe to keep up with each episode.

  The Tech Optimist welcomes questions, comments, or segment suggestions. Please email us at [email protected] with any of those, and be sure to visit our website at av.vc. As always, keep building.