Revolutionizing Cartilage Repair: The MACI Breakthrough with Nick Colangelo

[MUSIC] >> Welcome everyone, Dr. Garcia. Listen, I'm clicking way too many buttons here. I've got the title page. We've got music going on. Our guest has given me a heart to know about talking. So he's not even on the show yet. And already giving me a hard time about yippity-yappy. Welcome everyone to sports.talk. I'm Will Sanchez along with Dr. Garcia, Dr. Garcia. How are you, buddy? >> I'm awesome, I'm excited for this one. I also love that our guest is giving you trouble already. This is going to be good. >> You're just like, I'm excited. >> I'm excited. >> Well, you know what, everyone knows we've got our, this is the new product we're going to be talking about. I got my new background, you never know what's going to be. So it changes every show, but we're really excited for this. I think this is something that patients don't know about. I constantly get questions, and it's actually not as much in the office, because they come, they already know what they want. But the patients said, I got on the street, they're like, hey, you ought to be excited. And I'm like, yeah, they're like, you'd be really cool. We could like regrow cartilage. Don't you think that'd be really cool? And I'm like, we actually can. And they have like, they're just totally blown away. So from a layman terms, this is one of the most common questions that I get when they find out that I do sports surgery. So I thought it was kind of good for the people out there to see what's out there, what's one of the sort of hottest, most talked about products. And I learned about this, and obviously we got super lucky, because the CEO wanted to come on. Nick and I were really excited to talk to him. So yeah, we're going to get into that in a second. For me, when I saw the product and I saw you posting videos or LinkedIn, and I was like, oh, this is pretty cool stuff. And it's just once again, we're always talking about innovation, we're talking about the future. We're talking about more importantly, what these products do for the patient, right? Because obviously you have, you know, your colleagues and then more importantly, it's the patients and how they benefit from this. So we're really excited about doing that. But first, you know, we're really excited about, we're really excited about the recovery shot. Why? Because we got a lot of love for the recovery shot because they helped you the patient, just as we were discussing. Dr. Garcia, talk a little bit more about the recovery shot. So big thanks to our sponsors. I mean, it's not, it's pretty much every day that I hear patients post-surgical say how much they're happy, but how happy they're about this. You know, the ability to get all these aftermarket things that they want, you know, patients coming in, especially in Seattle asking for like, I want everything, right? I want to have the best machines. I want to have the best recovery. I want nutrition. It's all there for the patients. It's a one-stop shop. It's really allows them to have the sort of extra stuff. And we're going to talk about cutting edge stuff today. You know, they get to offer that stuff from the rehab standpoint. So anyhow, so it's been great. Again, any doctor's search and interest in using it for their patients, let us know. And or just just talk to patients with Mike because it's easier that way. So thanks again, guys. All right, man, let's bring on our guests. Nick, Nick Kalangelo, welcome to the show. Thank you for taking some time. And being here, you have an awesome step and repeat behind you. I mean, that is professional. Dr. Garcia, we, I think I may need one of these cool step-a-repeats. I don't know, we're going to have to do that. We were talked about hats and things like that. But Nick, I think we have had a lot of guests on here. But I think you're the most professional looking. Well, I'm going to guess that's a good thing. And we'll take care of it. We'll take care of it. And you will get you something for your life. All right, all right. Let's make sure, make sure, you know, first off, I'm sorry, I'll take it over again. I apologize here. Your full Pennsylvania, right? Is that where you originally from? You originally from Pennsylvania or Indiana? Tell us a little bit about your background because, you know, I know you're on the East Coast. So we want to share some of that before we get into everything else that you do here. Yeah, so it's upstate New York. So that's where I am from. And, you know, actually just by way of background. So lawyer by training. And I actually started my career in industry about 30 years ago when I joined Eli Lilly. You know, I was really fortunate to, you know, start there as a tax lawyer. But, you know, after a few years, to actually be moved over to the business side, which doesn't happen very often. You know, ultimately became kind of the director of strategy and business development for Lilly's diabetes and obesity product group. And, you know, it was a great foundational experience for me because the product group president of the time was more of a commercial guy. And he said, "If you're coming over here to work for me, you're going out in the field to learn our customers." And so I was a sales rep for a little while, selling, you know, Prozac and Lilly's insulin products, which was great. And then, you know, really just kind of being in the middle of the whole product development, commercialization, and so on of a pretty important product group for Lilly was just a great experience. And ultimately ran Lilly's venture funds for a while. So, you know, over the course of my career, kind of just had a lot of business development experience, acquiring, developing, and commercializing products. And, and joined, what was the predecessor company, a Varysel, about 12 years ago. So, it's been quite a bit of time, but it's been a great, great experiences. I'm sure we'll talk about it. So, I think for the viewers, too, to know, obviously Varysel is the major company, right? And then we hear this word Macy, right? So, can you explain the difference in the two? Because everyone hears me, you say the word Macy, they look at you, they see CEO, Varysel, and they see Varysel in the background. So, it'd be good for us to kind of understand that better. Yeah, so Varysel Corporation is the company that commercializes, developed and commercializes Macy. So, you know, we acquired Macy back in 2014. So, the company that I joined was actually called Astrum Biosciences, and it was a company that was in the cell therapy space conducting clinical trials for the treatment of severe cardiovascular diseases. Basically, using bone marrow-derived, multicellular therapy, which was really attractive at the time. And, you know, cell and gene therapies weren't quite as prominent as they are now. But, you know, really represented sort of the next frontier of innovation in the industry. And so, I was really excited to join a company that was kind of on the leading edge of these emerging technology. So, that's what brought me to the company. You know, at the time, Sonofi, which is one of the largest pharmaceutical companies in the world, bought Genzyme, and after they bought the company, they decided to divest what was essentially the Genzyme Biosurgery business. So, they were a pharma company. They weren't really a Medtech company. So, they decided to divest what was called the cell therapy in regenerative medicine business. And that's how we acquired this portfolio. So, initially, it was the first generation cartilage repair product called cartocel. Episel, which is a skin graft product that uses a patient's own cells for severe burn treatment, essentially a skin graft product. And then Macy was approved in Europe, but not in the US. And so, part of our development of that product was that we ended up submitting the BLA to the FDA in the US and getting approval for Macy in December of 2016. You know, so essentially, that was kind of a strategic transaction for us that essentially took us from a development stage company to a commercialization company. And then we changed the name of the company to Barrecell. We moved our headquarters to Austin where our manufacturing is now. And so, it really was quite a transformative time for us. And as you alluded to Dr. Grant, you know, now we're seeing as kind of a leading provider of advanced cell therapies for the sports medicine and severe burn care markets. Highly differentiated portfolio of innovative advanced cell therapies and specialty biologics that essentially repair tissues of the store function. And we're really focused on changing the standard of care for patients with knee cartilage injuries. Yeah, so I think I think you did a good job of leading to this. I only recently noticed that here this little story from your reps. So basically, I heard a very positive story. How you basically, this was a hurting product in 2014. And I know that some of the reps are going to kill me for telling you this. But it was a hurting product in 2014 or not doing as well. And you basically found a way to acquire this. And now you have this situation where you, you have a sort of, I would call the golden ticket of cartilage where it's under this biologic option. It's been FDA-approved. And for those listeners, and I want to make sure Nick can respond to this, this is not easy to do, right? There are lots of cartilage surgeries that I'm telling you about that one, insurance companies won't cover. And two, they're not FDA-approved yet. So there's some sexy stuff in Europe that we hear about all the time. But you can't use it in the US. Or there's some sexy stuff we've talked about on the show. And you can't use it that frequently because it's hard to get insurance to cover it. This is an insurance-covered FDA product. So it's a big deal. And now it's one of the most popular cartilage products. And I'm going to probably be the most studied cartilage project. So I mean, I think that's, if you want to comment on the fact how you basically, how did you know this was going to be like this? Or an analogue to go into a big detail, but kind of that story. is kind of incredible. - Yeah, I mean, yeah, it really was because we were kind of really focused on focusing the predecessor company on which programs we should be, you know, obviously kind of bringing forward in the clinic. But again, you know, it was a pretty nascent industry at the time. You really want to diversify your risk in a higher risk development situation. And so we were very, very fortunate to sort of, I mean, Sonofi was running a process like, you know, many large companies do where they contact a lot of companies. And, you know, we were probably one of what were a few natural buyers of the business. We knew the cell therapy space. There weren't that many companies working there developed a great relationship with our business development partners in Paris at Sonofi. It's a French-based company and kind of entered the process late, but sort of ended up winning the deal. And to your point, yeah, at the time, you know, the whole business was doing maybe $40 million in revenue. It was kind of flat to declining. And we were able not only to kind of get the commercial business sort of growing again at sort of industry or above rates, but we also were able to get Macy approved in the US with a pretty creative regulatory strategy where we took one pivotal study from Europe, the extension study that I'll talk about later. The Cardicell data that existed in the US, and we actually didn't have to run any additional studies. And so we were able to get to the market very quickly with the pivotal data from the Phase III study in Europe, kind of leapfrog the competition first to market. And, you know, obviously that's allowed us to kind of achieve the growth that we've been able to achieve today. So it's been a, you know, like everything. It's a lot of hard work by a lot of really talented people. But, you know, it's very rewarding when you're able to take what was essentially, I'll call it a neglected business, right? Because Genzyme had bigger products that they focused investment on. And you see it a lot in the industry where companies, even my predecessor, you know, the company Lily that I worked at when we would divest products. Sometimes they get into other company's hands and they grow into being a multi-billion dollar companies like Barrocell's become. And it's really because you've got a, you know, focused management team that's really kind of nurturing the product, which, again, may just not have been as high a priority in the bigger company at the time, you know. - Well, put up that slide, the first one. So I think you, I think it'd be good for you to touch on and we kind of can, you know, I can also chime in too 'cause obviously I know this product pretty well. But I think for the viewers, I don't understand sort of what the, which we treat this particular card is damage you see here with the Macy. That's how it's delivered for all those listeners. But really sort of what is, what's unique about the Macy compared to other products out there? I mean, I've had my podcast, I've had every possible cardless thing I've talked about. So what's the uniqueness of this Macy procedure? What do you feel is the uniqueness of it? - Yeah, so Macy is the leading product for the company. So, you know, we just released our kind of preliminary financial results for 2024. And you know, Macy will be close to a $200 million product in 2024 growing at, you know, around 20%. So as you mentioned, it really has become the leading restorative cartilage repair product on the market. It's basically an advanced cell therapy that, you know, will show you more about that uses a patient's own cells to repair, you know, the damaged cartilage tissue and restore function. Macy's unique in that it's the first and only FDA-approved product that applies tissue engineering processes to grow a patient's own cells on a scaffold, basically, you know, using a healthy cartilage tissue to do that. And, you know, cartilage injuries, while everybody sort of hears more often probably about ACL tears and meniscal injuries. I mean, cartilage injuries are a significant issue. You can respond upon where, you know, basically cartilage is unique in that, unlike most other tissues in your body, which, you know, have intrinsic healing properties. That's not the case with cartilage because there's no blood vessels to bring repair cells. There's no baddocks to get rid of cellular and tissue debris and no nerve. So, you know, cartilage, a focal cartilage injury like wheat treat is like a pothole on the surface of the knee. And, if it's left untreated, you know, leads obviously to joint pain and dysfunction, but ultimately to osteoarthritis and partial lymphoma in the replacement. So, you know, that's the progression that we're focused on halting. - Yeah, that's perfect. And I think it's good for this slide. I'll show the listeners, but basically, there's three types of cartilage stuff. So, you have the ones you clean up, which is what a lot of people as you do has been around for a long time. And yet, the micro fracture and the drilling that's a little bit more old-schooled, but it's not really just sort of trying to repair and try to fill it with something good. And then these are sort of the main products. And obviously, ACI, so the viewers don't list the, to not get confused, ACI and Macy, ACI is just the older version of Macy, right? And so, now we have this better matrix. So, obviously, before we had to use the periostial air, which was as you can put it, it was more challenging, right? So, now it's a lot easier to do these procedures. I think this is kind of a good side to bring up. So, you know, you guys went from sort of this, our throttomy car to sell, then you join the company. The company takes off 2016 big jump, right? Like it just was a lot different. And so, you guys described that process briefly, sort of, you went from now, like, where did you, how did you go from this, this really tedious, so well, this used to take like three times longer, and then they figured out a way to make it so it did. So, how did you guys do that? You know, what was your thought process and going from that to this sort of 2016, 2018 product that's now, you know, much easier to use and much more reliable? - Yeah, so, you know, in the U.S., so when we bought the business, Macy was already approved in Europe. That's where the technology was developed by Dr. Peterson and Sweden. It was approved in Europe. A car to sell was the product that was shown on the left hand side of that slide. That was the product that was approved in the U.S. when we bought the product. And as you mentioned, it was a first-generation ACI, so that's Autologous Condorcite Implantation, so taking a patient's own cells and implanting them in defect. First-generation ACI product that was really, but first commercialized in the U.S. in the 1990s. And, you know, as we'll talk about with the Macy procedure, what ends up happening is that you can explain it, you know, add any color that you'd like. But, you know, when you suspect there's a cartilage injury, you know, often you'll go in and do what you've referred to as sort of the palliative techniques, the duaconda plastic, a diagnostic arthroscopic procedure, just to see what's going on in the knee. And at that point, that's where you take a biopsy of healthy cartilage for, at the time, cartocell and now Macy. So, out of a non-tick-tack-sized biopsy, out of a non-weight bearing portion of the knee, that is sent to our manufacturing facility in Boston, where we process the biopsy. We isolate the condorcites, which are the cells that make cartilage, and we expand those cells, and then we cryopreserve them. So, we freeze them down, we wait till surgeons like you are and the patient are ready to move forward with the surgery. Once that happens and you pick your surgery date, we kind of work backwards, we thaw the cells, we further expand them, we seed them onto that collagen membrane that's shown in the second image from the left. And a density of about half a million to a million cells per square centimeter, packaged it up, send it to the surgical site where the surgeon obviously prepares the defect, and essentially cuts the macy membrane to the size of the defect, we lose it in with vibrant glue and is done. So, in the case of cartocel, which was the predecessor product, the front end of that process was essentially the same. Take a biopsy, expand the cells, but as it's shown in that vial, the final finished product was the liquid cell suspension. Now, you can imagine that you alluded to this, how hard it is to fill a pothole on the knee with a liquid suspension, right? We'd like to try to get that in the smaw word. Yeah, you know, we'd like in it to kind of spackling, you know, a wall, you know, with water, right? I mean, it's very hard to do. And so, what that required was opening up the whole knee, as you alluded to, you've taken a periosteal harvest off of the shin bone, micro suturing that into place, injecting the cells. So, it was highly invasive, technically demanding, very time consuming. And so, it became kind of a niche product at the kind of high-end cartilage repair specialist. And that's because, again, it's really the way one of the only ways that you can truly repair the tissue because you're using a patient's own cells to regrow that cartilage. Around year 2000, a company called Verigen Europe developed based. which was a next-generation cartilage repair product where those cells were seeded onto the membrane as I just described, and then Genzyme acquired Verogen in 2004. We acquired the business from Genzyme, and that's how Macy sort of made it into our hands. And as I mentioned, you know, it wasn't approved in the U.S. at the time, we ended up submitting the BLA in 2015, the FDA approved it in 2016, and we launched the product in 2017. So the real sort of, as I mentioned, you know, this was kind of a niche product, you know, used because there's actually 20 year outcome data with cartilage, with cartocel now. So once you regrow this cartilage, correct me if I'm wrong, but it can really last a lifetime unless you have another injury, right? So that's why surgeons would take the time to do that. You know, the beauty of Macy, and you see this often in the Medtech industry that when you take a highly invasive surgery, open heart surgery, and then you kind of progress to minimally invasive cardiac stents, you see that there's this broad adoption as the standard of care changes, and that's really what's going on with Macy right now. So because you have this product now that has the cells already on the membrane, as I mentioned, as you can see in the third image from the left, we actually developed custom cutters that actually would make an open Macy procedure. So it went from highly invasive to a many arthrodomy, kind of trying to make it even simpler and less time consuming, assuming for surgeons in an open procedure by developing these custom cutters that would allow you to score the cartilage and then stamp out the membrane, exact size that you could then glue in. And really that was a big technological advancement that they did a less invasive, faster, simpler surgery for the surgeons, and that's why our surgeon bases grown so dramatically since the product. Nick, I want to stop a second. So first off, that's great. So I think for the listeners to hear what he's saying, you know, they basically took a very challenging situation and they keep making it simpler. I know people always think simpler is, you know, never good. You want complicated. But in this stage, we want it simpler, right? The less time under anesthesia, the simple cutters, you want more adoption. And then the more adoption means more people could see it. So the idea that behind this is pretty cool. And I think will you, I don't know if you have any questions about this, but he basically just said to the listeners that we're going to take your cartilage, we're going to send it to Boston, we're going to grow it, we're going to freeze it, it sounds like a movie, right? And then we're going to send it back to you in a box. And then it's going to be sterile. And then you're going to glue it on your knee. And when I tell it to patients, they don't like they're like, what? Even that can actually work. I don't know if you've anything else, Will, you want to chime in being late. You know, you're, you know, you play doctor on TV, but well, just the fact that it's a, you know, regenerating cartilage, right? And utilizing this component, and I could imagine, right, we talk about sports, you know, on the show, the, the athlete now is recovering faster, long-term effects, the flexibility, right? When you think about what you're utilizing as this component. So I know if, especially if I'm an athlete, but just anyone else that I can have mobility, quality of life, you know, in movement, utilizing this, that, that's all you want, especially after you've suffered an injury to kind of go back to, you know, this, this normality. And I think what you guys are hearing from Nick too is you have this product, right? Like, so the product has been around for a long time. And then every time they make a tweak to it, right? Like you don't want to make big tweaks with the FDA and everything else. But you know, they found like, we have this really great product that works. How do we make it work better? So how do we make it work better open, which is with the bigger incision? That's with those cutters. And now, which we'll talk about, and I don't want to give away too much behind me, but the arthroscopic approach to do this, which again, the goal here is extremely high technology, very small incisions. And we can get to that. That's like sort of the perfect, the perfect formula, which we've finally got to. Nick, very briefly, can you kind of touch on touch on the slide and explain the dual membrane ideas so people can understand and we'll show how regrow is in a minute. Yeah. So, you know, as I was describing earlier, once we expanded the patient cells, they're seated onto this collagen membrane. And there's a dense side that is on the top. And then a kind of less dense side on the bottom. The way we seed those cells is you kind of flip it over. And, you know, conger sites are spindle cells. So they attach themselves to those collagen fibers. And then when it's implanted, it's the dense side up, the sort of cell side down. And once the implant or the membrane is implanted at the bottom, as you see here, those spindle cells kind of migrate down to the subcontra bone. They start producing extracellular matrix, which is essentially the cartilage. And it fills that defect from the bottom up and allows patients as will alluded to to kind of resume their normal activities. Right. So our core patients, and I'd be interested in your take on this Dr. Garcia, are really those sort of younger active patients. So, you know, think about a bell curve from sort of late teens into early 50s. Think in the summit pivotal study, average age was about 35 same thing in the publication of the first thousand patients we treated in the U.S. So it really is that patient population that is suffering from significant knee pain that wants to fix the cartilage injury and get back to their sort of normal activities. Well, and I think what's interesting is we'll can see that. You guys all I'm sure the viewers saw that how it grows back. That's literally how it works. And if you skill patients at three months, six months, nine months for other reasons, or they want to have, you know, there's some issue they're getting stiff or something because again, we all do these surgeries, you want 100 percent, but the word 100 percent never exists. But if you go in there and you take a look, you can actually see that at certain stages, there's ways this thing looks. And when it gets up to the full stage, and I know because I do a lot of these, you can't get that cartilage off. Like Nick keeps saying, like when you have a solid regrowth, well, it like literally like even a night, you cannot take it off. Like the first time I saw it, it's very hard because you have to, if you're a surgeon it had never seen one of these before, it's very hard to process because we're not used to products that do this. But when you see it, you can literally put your finger on it and it feels just like the rest of the knee. So the ability to regrow when you've been around for a long time and knowing that it doesn't really happen that often, that we get really good regrowth of cartilage. It's just mind boggling. I remember the first time I saw when I was like, I called my rep and I was like, this actually works. Like it legitimately regroup. It looks just like the other stuff. And if you were to, you know, you core out things or do things around that area, if there's, if there's a part of it that you don't fully regrow and you have to redo something, you can't get rid of that other stuff. It's like stuck on, it's just like the solid good stuff. Well, I don't know if that's any, if you have any questions about that, that is a nice interesting. So obviously, you know, with something like this, we're talking about maybe severe cartilage damage. But have you seen anything come across your operating table where it's minimal, but based on the athlete or the patient, you're kind of going in and using this technique to make sure that whatever you're working on is extra sturdy because of this product. Well, Nick can probably jump on this too, but I basically, you know, we don't do this as preventative, but we do prevent other things, right? Nick, I mean, the idea is that you put this cartilage hole on one side. She prevents damage to the other side. Imagine this. Well, you got a tire and you got a road, right? The road has a pothole in it. You'll damage the tire or the tire has a nail in it. You don't want to damage the road. So if you fix one side, you avoid damage to the other side. So that's the preventative nature of this. It's still an invasive surgery, and Nick, you know, we're talking about 10 months to a year of recovery. You got insurance authorization, everything else. You don't want to go through this willy nilly, but these patients are, as Nick will tell you, these patients with cartilage damage are much more severely impacted than the ACL tires. Agreed. Yep. So the, I think one we can chime in is, you know, you guys have done, if there's a couple studies we've seen where it shows all the cartilage servers, and it shows the number of research projects, research studies. Macy will has the most research on it of any of the current cartilage products in the market, which is pretty crazy. So when people ask, like, is this been around, do you trust the results? You know, if you don't trust the results of this one, you shouldn't trust any of them, because, you know, there are some strong results. But I mean, I don't know if, you can, I mean, it's amazing that you guys just continue to, I mean, Nick, you have so many projects out there and so much research out there. Why keep doing it? You know, you have so much data already. So explain what's the desire for Macy to always keep doing it, keep getting better, right? Like you've already, you've already won the game. So why do you keep doing it? Well, you know, I do think, you know, one of the advantages, well, several advantages to Macy that we talk about all the time. First of all, Macy has a very broad label that basically covered the indication for Macy covers, you know, single or multiple defects anywhere in the knee, you know, regardless of whether there's bony involvement or not. So it's applicable for a large number of patients and really has unsurpassed clinical data. So Macy is the only FDA-approved product that demonstrated superior versus micro fracture, which Dr. Garcia mentioned, which is what the FDA requires as the comparator in these phase three pivotal studies. So the summit study, which is the Macy Pivotal study, basically demonstrated statistically significantly greater improvements in pain and function versus micro fracture at two years. That's the common end. And then there was actually an expansion phase of the study that went out three additional years to five years. And the FDA was very interested in making sure we included that data in the label as well, which showed that the improvements that we're seeing at two years carried all the way out to five years. So that's a pretty significant sort of longitudinal data that's in our label to begin with. But because Macy was approved in Europe and Australia since kind of the early 2000s, what you're seeing now is even last year in the American Journalist Sports Medicine, there was a publication of a prospective 10 year outcome study, which showed positive improvements for Macy out to 10 years. And even one other publication out to 15 years. And as I mentioned, Cardicell has data out to 20 years. And so it is really important, especially when you have kind of an innovative premium priced kind of product that, as you mentioned, is covered by all the major insurance plans in the country that you can continue to demonstrate that this is really kind of a restorative procedure that can last as mentioned. And I don't want to interrupt you, but I want to bring that point up me to set. So you just said an expensive product because that is a common misconception for patients, right? And I'm just really important is I want the viewers to hear this because I bring this up on every single talk and no one listens to me because I'm a doctor like this is an expensive product. This is a pharmaceutical product. So it's very cool because you guys got a pharmaceutical allocation. I mean, you have a lot more rigors. You have to go through correct right for the biological stuff. But this is a pharmaceutical. So this product is paid for by the insurance company is not paid for by the patient. It's not paid for by, you know, the hospital. It's paid for by the insurance company, which we all know in the news that is not that that's the one we're okay with them paying for it because they're doing pretty well. But the important thing I think is for people to understand that while all this product is expensive for the insurance company for the patients, it's the same as anything else. And that's and now you get this superior product. So it's really important people to hear that I think because they hear, oh, you know, this is how it's so fancy. It sounds like the Mercedes Benz or the BMW of products. Maybe I can't afford it has nothing to do with that. This is an insurance provided coverage. Yeah. And you know, the interesting part of that. So as you had alluded to, you know, unlike most devices in the MedTech industry, you know, Macy is actually very different. So Macy is actually regulated by the FDA as a combination product. So there's different combinations, you know, there can be a drug device like the drug eluding stents, etc. In this case, you know, Macy's regulated as a biologic device product with the college and membrane as the device component. And then of course, the patient's own cells as the biologic. And that has a lot of important implications, you know, in terms of the regulatory pathway that we had to pursue to get the product approved and on the market in the US. Intellectual property protection. And as you alluded to, how the product is reimbursed compared to a typical product device. So, you know, because Macy's biologic, it had, you know, for example, additional 12-year data protection, which is afforded to all biologic products in addition to patent life. It's actually reimbursed under a J-code. So it's not part of a CPT code professional fee for the surgeon or facility fee. There's actually a J-code that's listed in the compendial like other biologic pharmaceutical products that is reimbursed by the patient's insurance plan, as you mentioned. And I think, you know, an important part of that, first of all, you know, well over 90% of the submissions for approval get approved, right? And a lot of that has to do with Macy differs a little bit from a normal biologic or drug product, which are dispensed in a pharmacy, right? So every insurance plan has a pharmacy benefit that we're all familiar with. And a medical benefit, which is what Macy's come for. A pharmacy benefit, you know, basically the manufacturers kind of discount to get a formulary position. And then once it's sort of on a formulary, you know, your physician can write a script. Nobody really says Dr. Garcia, do you really have hypertension? It's just sort of managed by where they kind of discounted on a formulary tier. In the case of a product like Macy, that's reimbursed under a medical benefit. Again, every major plan in the country covers it. And they basically have to approve it in advance of the surgery. So there will be an, you know, pick a blue, blue cross blue shield plan. It'll say a patient's mouth, you know, eligible for Macy if they are this age with a grade three or four focal control defect, their ability, you know, they have an ability to do the rehab, et cetera. The point being that the insurance plans know that every time Macy's being used, it's on an appropriate patient. So they know the price, they know the clinical benefit, they know, you know, the patients are going to benefit from that. And that's why you get the prior approval. So I think one of the things that the company has done over the last decade is really sort of unlock a lot of value because we try to carry a lot of that load for the surgeons in terms of the benefit coordination between patient, surgeon, the insurance plan to make sure that the submission is done in a timely fashion, doesn't sort of slow things down for when the patient and surgeon want to, you know, have the surgery. And we invest a lot in that to make sure that, again, it makes it as streamlined as it possibly can be. But that, you know, that is an important point that you brought up that, you know, when an insurance company is able to know that they approve every patient before the products used and they know the benefit, that sort of, you know, erases the whole sort of, you know, kind of, I won't call it a phantom objection, but, you know, discussions around the price. Well, we've seen it. We've seen it right, Nick, on the internet, you see all these papers with as someone posted, like, look at my rejection from my surgery that I need. Look at the rejection from my surgery that I need. You don't get it with this. And I think, well, we should, for the listeners, you know, we just keep hurrying this, right? This is an innovative product. And I told you that, you know, this is obviously, it's a pharmaceutical, it's expensive for the insurance company. But if, listen, the insurance company would never approve it if it didn't work so well. That's the point we're trying to make. You have a company that you hear about all these insurance companies and how they're very stringent about costs, right? So if this is, this has to be a product that has such a good quality of life improvement that they're willing to pay for it. And so that shows you the value of this because you've already, this, it's approved with pretty much any insurance. Like, people come in and like, are sure my insurance will cover it. I'm like, I'm pretty sure that it will turn. So it's very rare that it's difficult to get approved. So will that's interesting, right? Like, you have something, it's like basically like, you have a, you have insurance companies that we hear all these things online. We're not going to have a whole talk about that right now. But the, you know, you hear all this stuff online about these insurance companies and you know that they're very stringent about costs. And now you have a product that they're willing to do reimbursement for despite the cost because of the quality of life because quality of life is a really big deal. But you get your ACL tear and you don't get it fixed. Sometimes you can get away with it and you can run around with it and you can do things. When you have a cartilage hole will, it really, really hurts. It's, it's, it's, it's, it's up there to like, near arthritis because actually it's pre-arthritis. And so that's something that's really important for the listeners to hear. They think cartilage hole, that's not a big deal. But they hurt way more than anything else. These are my most satisfied patients, my cartilage patients. And I would say there are publications out there that show even though Macy is, you know, may cost more upfront over the life of the patient or long term, it actually is equal or less than some other options that could have been done by the time you add in what will ultimately have to be done in it. And just to kind of reinforce that innovation point, when you think about the cost of Macy, you know, compared to gene therapies that can be in the million to two million dollar range or or cartilage cell therapies, which are half a million duration. I mean, yeah, that's the kind of innovative manufacturing and other development, you know, processes that you have to go through. But again, it's nowhere near that kind of price point. Yeah, and it's important what you said, once I can report what you said is like that the, this, when you do lesser surgeries, well, in these cartilage stuff, people fail, and like they come back and we're talking about my average cartilage surgery patient or sometimes I get to them, six surgeries, five surgeries, women's life I could do it in one surgery and avoided five more. And so you imagine that what he's saying is like maybe each individual surgery is less expensive than the Macy, but it's going to prevent long-term. And I've seen what you're talking about. So sorry, Will, I just want to bring that point out. No, it's fine. It's right online kind of what you guys are talking about. I just wanted to ask Nick if he's got into feedback from a patient, a doctor, something that really resonated with you, saying, "Man, your product either saved me money or saved me from going back and having multiple surgeries changed my life." What's the story that you went home and you told your significant others, say, "Man, this is why we do it." What's that one that sticks with you? - Well, we have all sorts of basic patient videos of what it means to a young mother who couldn't walk up and down the stairs with her baby and how it changed her life to be able to do those things. And that is exactly why we're doing this. And it's interesting, this is a good time of year. We typically, and we'll do it again this year, we'll be at the Super Bowl for Radio Row and we go on a lot of the sports medicine or the sports channels. And one of the folks who would do it with me in the early days was Derek Torres, who was an Olympic athlete. She actually had Cardicell in her left knee and she was one of the first basic patients in her right knee. And she was actually able to go back and compete in the Olympics after she had her first surgery done with Cardicell. So those are the kind of life changing outcomes that she was one who would talk to me about how hard it was for her to even walk up the stairs let alone sort of train for the Olympics, right? And so that's kind of a, you could probably say that about almost every patient we treat. They couldn't do the normal things that all of us do or whatever athletic activities and, you know, Macy allows them to do that, which is obviously extremely rewarding. - Perfect, yeah. Yeah, well, I think that what he touched on is perfect. I think I don't want to pivot, but obviously we still have a little bit of time with him. So I promised him that we would pay under an hour. He didn't know if we could make it to an hour. I think we're going to go over. So that's all we're going to have to end up cutting down. But the, well, took off that side for a second. I want to bring up this point, I want to ask him. So I think we've talked a lot about, you know, you did some awesome job talking about the business behind Macy, which I think is super unique. I don't ever get to hear that perspective. We don't ever hear that because we're mostly focused on the medical side of things. But for the listeners, we like to start from the ground up, you know, like with napkin or reality, which is one of our first shows. Like how do you take something small and make it something big? And we have the man here that did it, which is awesome. But so, but Nick, there's obviously the post part, which is, or the stuff is like, you have this awesome product, right, you keep making modifications to it, you keep making it better. But there's something unique about you guys that I wanted you to talk about. So when it comes to like informing people, you have different ways of doing it, right? You guys have, and you have Carla and other people in your office that do amazing job. But you know, you do local labs so that people locally can find out. You have people like me that fly around the country to talk about your product. You have different directors that talk about your product. But you guys do so many things, and there's some will. You've seen me do this, you know, the headset thing I did on Friday, that was Macy. So like they're so into like every possible way we can show people how to do this surgery. And they're dedicated, right? Like I just got on a phone call this morning, I was talking with the entire team on why I did the certain steps. And they're just so into like, how do we get better? But it's, where does that come from? Because I've worked a lot of companies, some do some things, but they don't go to the extent that you guys do, which is like, I wanna find every possible way to teach someone about this. And it doesn't mean sell it, don't go sell the product card. Just tell us how you do it, and how we can make it better. Yeah, you know, I think it comes back to, you know, we have a unique sort of place in the industry. And it's certainly the case with Macy where we get a patient sells. We know every patient that we're treating, right? We're not stamping out a million, again, hypertension pills, and they're going to whoever they go to. I mean, it's a very patient centric and customer-focused group. And that's true for Macy. It's really true for the catastrophic burn patients that we treat, you know, with epicell next to their product. So that kind of culture, we're focused on the patients. We wanna make sure surgeons really understand how to identify appropriate patients, make sure we have good clinical outcomes. That just kinda is built into the DNA of our company. And you're right, we invest very heavily in surging peer-to-peer educational programs, including these bio-skills labs with cadaver needs and things like that. And in fact, you know, it's really the largest discretionary commercial budget item that we spend money on, right? 'Cause, you know, when we do these programs and we fly surgeons in from around the country to train over the weekends, et cetera. I mean, it is a big investment. But, you know, again, it's all geared towards, we wanna make sure, first of all, we're so fortunate that we have surgeons like you and dozens of these passionate dedicated surgeons that we partner with to make sure we're bringing quality educational programs to surgeons who are interested in sort of adding Macy to their practices and treatment algorithms. And, you know, it's definitely the most important thing to do, again, to make sure we optimize patient selections outcomes and so on. So, you know, it's really just that. It's just sort of built into sort of how we operate and what we do. We, you know, we have an advisory board, we have speaker bureaus that we partner closely with. We wanna know from the surgeons sort of, how can we best teach other surgeons, right? So, whether it's educational content or new technologies that we can leverage to make sure it's easier to consume by the surgeon customers. I mean, we're just always interested in that feedback. And, I think, you know, as we were developing the Macy Arthro Instruments, that was an iterative process where we would develop prototypes. We'd have surgeons come in and work with them, make tweaks, develop, you know, come back with another one. You go through that four or five times and again, it's just about getting that input to make sure we're kind of delivering the right innovation and technology for the surgeons in addition to the educational component. - All right, so I know I see the timer clicking down and I need to get to this last topic as no one has any idea what the thing is behind me. And we've been here for 46 minutes and 53 seconds. So, let's go to the next, Nick, I appreciate everything you said, this is awesome. So, well, I'll say you keep hearing all this stuff. We got this sexy carloid surgery. We can grow it in the lab, we can glue it on your knee. But until a year ago, other than some kind of off-shoot random stuff that you people were doing, there was no way to do it through an incision this small. All right, it's always been incision this small. Long in my hand, big incisions open. I said every time I told patients, I was like, I'm just gonna be an open incision. The first step is like, scope, that's easy. Second steps open, you'll get through it. Not a big deal, but it's open, it's big. And there was a lot of work that went into this. And it took, I was involved in this FDA trial and it's different than other companies, right? You can't just start a tweak the product a little bit and get it because it's a biologic, Nick. And we don't have to go too much into it so we can show the product. We don't have to can pull it up. There, you have to do a lot more thing. We had to do the FDA trial to show that it was not damaging the cells. And normally you wouldn't have to do that, but only because you're a product, because it was so stringent because of the FDA. You had to basically show this product just as good as the open one, even though it like all of us kind of knew that. But you had to do it for the FDA and that's, you had to do so many extra hoops that the average company doesn't have to do, is that correct? - Yeah, that is, you know, when you develop kind of an instrument, it's set like this for the arthroscopic delivery. You know, there's multiple work streams, right? This took us two or three years to kind of develop. There's the instrument development itself. And, you know, obviously that involves, as I mentioned, sort of the design phase of it, where you develop, you know, you work with a vendor, we have a local vendor that, you know, they did our custom cutters for, or they'd done another work for us, the instrument kits for open, et cetera. You know, we work with them, we develop prototypes, we have surgeons come in, we refine it, you get, you know, that probably took almost a year till you finally even get to design phase. Then once the instruments are done, you go through a whole sort of set of validation, testing, et cetera, to make sure that they meet FDA requirements to make the instruments commercially available. Now, at the end of the day, as you alluded to, I mean, these are class one devices that we actually registered before Macy Arthro was approved. But that was just the device component. The trick here was that, you know, because Macy's approved under a biologics license application, to be able to add the Arthroscopic Administration to the product label, we actually had to do what you were referring to, which is a human factor study that says, if we give surgeons this set of instructions, can they reproducibly basically administer the implant using these Arthroscopic instruments? And so to get it on the label, so that we could promote the instruments and then teach surgeons how to use them appropriately. We had to go through that, was essentially a 10 month FDA review process, which we obviously were able to do successfully, which was just great. I think Will, I can say it now, the trial has been approved, but Will, you get a phone call, you got to fly out to Boston, and then they don't tell you how to use it, and they want to see how you do it without that in a black box. And then you're on a video camera, and then they say, "Here's four different ways to do it." Let's see if you can do this without any instruction. And if you can do without any instruction, then we know it's safe. And that's what they did for, what, 16 or something, there's more than any more than that, surgeons. But basically, that was the game. It was like, almost a game, but it wasn't really a game, because if you don't do it right, either you're out or the FDA trial doesn't work. It's the old version of Squid Games, I got it. But, you know me long enough that we love the game. It was a fun game, but you're under scrutiny for it. But you can see, guys, I mean, think people, they found surgeons they thought would do a reasonable job. They flew them all out there to do this, just to show that this product was safe, to put in the scope. So, when people ask me, what do you think of this new thing? I'm like, this has been tested more than anything I know of, right? You guys have gone through so many hoops, but now you have this product that basically we've done five of them now, and first one is Pacific Northwest, and we have this product that we can now insert this product that's 20 years tested through a scope, through an incision this small. I mean, what is your feedback then so far? I mean, I don't, I could go on and on about this part. We've seen way too many of my posts, but Nick, I want to hear from you. What is your feedback then on the company in the first six months of this new product? Because it's been out since, you got approved at the end of August, is that correct? Yeah, and kind of, yeah, kind of launched sort of at the end of the third quarter, and you know, the physician feedback, surgeon feedback has been great. You know, I think in the market research we did before launch, you know, whether surgeons were Macy users at the time or not, you know, there was a high interest level, you know, surgeon said I would expect to do more procedures, or even if I wasn't a user, I'd shift some of my procedures if a Macy Arthro option was available, and you know, so we have seen that out of all of our surgeon segments. So we have, you know, folks like you who are, you know, strong users of the product now doing Macy Arthro cases, we had sort of our original set of surgeons that maybe hadn't adopted it yet, they're starting to use it. And then we had another set of new surgeons that really just do arthroscopic, you know, procedures that had never even used Macy, and we've seen sort of cases scheduled, they're completed out of all of those segments. So that's great from a surgeon perspective. And then from kind of a patient perspective, as you know, Macy Open is kind of a go-to product if you have a deep defect on the back of the kneecap or the patella. If you have a larger defect, four square centimeters or above, that's kind of like the go-to for Macy. But we've seen since we launched Macy Arthro, and not only are you seeing these procedures, you know, the whole thing was designed to be to treat two to four square centimeter defects on the femoral condyle, which is the largest part of, you know, the Macy addressable market because you can explain this better than I, but you know, the end of the thigh bone, you know, bears a lot of the weight, and that's where you get a lot of the injuries. And there's just more smaller than larger. So that's what we were designing the instruments for, but we have seen now that those instruments are being used in the trochlea behind the patella. You actually had a patella case where people can lift it up into the patella without having to flip over. That's not easy to do well. I haven't tried it. It doesn't look easy. It's not easy to do. But that's impressive. All right, keep going. Yeah. So that's the feedback. So just kind of on surgeon use of Macy users and non-users using it in different locations of the knee, not just the femoral condyle. And then I think what we've seen anecdotally, and you can share this better than I can, but you've seen what the reason the surgeons were interested in it, based on our market research was less invasive surgery, less postoperative pain, faster postoperative recovery, better aesthetics. And so you see these things on social media where, you know, they're talking about range emotion being, you know, significantly better than you would see from an open procedure. And so on. So I think, you know, that's something we, to your point earlier, we have, you know, different, you know, we have a registry going on now so that we can look at those early post surgical outcomes. And I think, you know, because we didn't do a clinical study, you couldn't measure them prior to approval. So that's something we have to do post-approval and, you know, hopefully, you know, that kind of bears out that you're seeing all those benefits that you would expect from less invasive surgery. I, yeah, I think that you might have been one of my LinkedIn posts then. So yeah, that's the, yeah, no, but Will, I mean, I think people, you can't slow them down now. They get this surgery now and before, it was a lot slower and now you can't slow them down. I mean, I've had, out of the five I've done, I've had three rep had to tell them to stop moving so fast. So that's a good thing when you're slowing the patients down that much, Will. So anyhow, so the, I think Nick, we don't want to cut you off too soon, but I want to make sure you have a few minutes. If you got about like two minutes, can you talk about what you think the future is for this? Yeah. Well, you know, for Macy, generally, you know, we think, because again, as I mentioned, we're still, I mean, we're eight years into the Macy launch, right? And you're still seeing this prod a grow 20% a year as we're adding more surgeons. You know, we look at how many biopsies or surgeries are done per surgeon as surgeons kind of identify more patients within their practice. So, you know, we think the core Macy, you know, will continue to grow. We think with Macy, our throw on top of that, there's an opportunity, you know, for better patient outcomes and more surgeries. And then, you know, Macy and other joints. So we expect to, you know, there's cartilage on the end of all the bones in your body, particular cartilage. And you know, the next biggest opportunity is in the ankle. And so we've been working with the FDA on kind of developing the plan for us to launch a Macy ankle study, which we expect to do in the second half of this year. So, file an IND in the first half of the year and then initiate the study in the back half of the year. And we think that will be, we already know, you know, we can't promote it because it's not in the produce, but there's certainly publications out there of surgeons that have had treated ankle cartilage injuries with Macy. I mean, it's been used in the hip shoulder. Again, we can't promote that. And you know, in some of those other joints having an arthroscopic option will be important. 100% especially the ankle, but that's the, I mean, you're getting to the perfect topic. I think the, for the viewers, this is a knee surgery product. Offlabel uses the other areas, but coming down the line and you heard it from the man himself. Okay. So that's the plan. And once now that we've built our new manufacturing facility, which you need to come up and see in Burlington, which has its own training lab. So you, I think you'll enjoy doing that, but that also has been, you know, this facility has been built for global, to meet global manufacturing requirements. So we're doing right now an assessment of sort of OUS opportunities in Europe, Latin America, and certain countries in Asia. So that's an exciting opportunity for us as well. That's awesome. Well, Nick, thank you so much for being on. I don't want to cut you off, but you know how the social media is likely to be go over an hour. But like I said, I think, I think I told you so, Nick. It went to an hour. One quick. Yes. Well, hey, you said you're going down to radio row, getting ready for the Super Bowl, down in New Orleans. What are you going to do? John Malaya, Ben Yees, what is the gay plan? We don't care about anything else. What's the food that you're going to consume? It's going down to New Orleans. It is absolutely delicious down there. So I told you I grew up in upstate New York, when the builds got bounced, and we're going to let you-- It's forcing you to go down there. We're going to let the team take this one. I've been to a number of them. So other members of our team and other surgeons actually have a great guy, a former NFL, Solomon Wilkotz, who was a CBS announcer. I remember the Bengals, he kind of does it with us, and so there will be other surgeons from around the country that do that as well. So I will be sitting this one out unfortunate. It makes sense. I've got a lot of friends. I'm originally from New York. I got a lot of friends back in New York that are-- all I said was, I'm sorry, and I left it as that. And we're going to move on, because I don't want to end this on a bad note, and I want Nick to be upset with me. Dr. Garcia made me ask that question. I'll just say that. That's true. It blame me. Thank you so much for being a part of the talk. We appreciate your time. This was fantastic, and I hope everyone got some great information out of this. Thank you. Really appreciate it. Thanks, everyone. All right. Take care. Have a good night. Bye.