Benjamin Holmes, Chief Executive Officer at Nanochon

Jesus Moreno (00:01.228)
Welcome back to Global Trials Accelerators, the podcast where we dismantle the barriers to clinical innovation and explore the strategies driving the next generation of life-saving therapies. Most Class III device companies still assume their first-in-human data has to come from Western Europe, Canada, or Australia. And that assumption is exactly what's starting to break. Joining us today is Dr.

Ben Holmes, CEO and co founder of Nanochar. He holds a PhD in biomedical engineer from George Washington University, a BS in mechanical and aerospace engineer from the University of Virginia, and has spent the last decade turning 3D printed biomaterials into a real implant for cartilage repair. He's raised nearly $12 million across NSF grants, venture capital, and

non-dilutive awards, earned FDA breakthrough device status for Nanochance Condograft, and just weeks ago received Panama's approval to launch the company's first inhuman trial. Today we'll look at why Let America is becoming a serious option for early feasibility data and novel devices and what is actually happening in the region as well as what it takes

To operationally stand up a first-in-human trial from scratch. Ben, welcome to Global Trials Accelerators. We're excited to have you here.

Ben Holmes (01:35.91)
Thank you. It's a pleasure to be here. Thanks for having me on.

Jesus Moreno (01:40.992)
It pleasure is all ours. Ben, I would like to start from the beginning. It it is my understanding that you and co-founder Nathan Castro met in Grace Sang's tissue engineering lab at George Washington. you coming from a mechanical aerospace engineering, him from a biomaterials focus.

Tell us a little bit about that moment. What was the how did the realization that those two backgrounds could become one implant instead of two separate research papers or two lines of research?

Ben Holmes (02:25.2)
Yeah, yeah. I'm very happy to tell that story. So you know, n d Dr. Castor and I weren't just colleagues in Grace's lab. We actually joined her very early on in her own career. I think that she'd only been in the university for maybe like a year or two. and we were actually her first two PhD students. So when we started in the lab, it was literally just the two of us for like that first year.

and then some other some other PhDs started to filter in. we also were very active in supporting masters as well as undergraduate volunteer students. so you know, over the next couple years the lab grew. but we in the beginning was just literally the two of us at the same bench. and it it it sort of just helped us form a very natural collaboration.

because you know, two people alone in the lab all day kind of try to do the same things, you know, trying to get trying to kind of get this lab off the ground, help get this lab off the ground, while also having all the normal sort of you know pressures and requirements of a student in academia. I we just sort of became you know very good colleagues and fast friends, right? So I think we just in general had a natural deeper level of collaboration and communication.

than might be typical in an academic lab. And then I think to your further point of how did we realize that we could come together and collaborate on a project like NanoCon, you know, we had a lot of complementary research. you know, the lab was at the time broadly looking at different types of advanced manufacturing, not just 3D printing. So so actually my first projects were in electrospinning.

and then Nathan was really kind of working from his chemical engineering background, was really looking at material design and material selection. But I think what was interesting is he was sort of looking at how you can design these materials to have certain mechanical properties, certain biological or physical properties to get a biologic effect, and then how can you optimize some modality of manufacturing.

Ben Holmes (04:47.974)
And then to your to your point about our backgrounds, me being more of a mechanical engineer with more of a design background, I actually came from the construction industry. So I was doing a lot of like CAD design and structural engineering before switching into biomedical. so I knew how to take kind of existing base tools and try to adapt them to create something more informed. And so we actually both had kind of like adjacent cartilage projects, but by the way, neither of which ended up being the nanocon technology, but

you know, he was doing a lot of work in in trying to get cartilage-like synthetic materials to bond chemically to bone-like materials. And then I was doing a lot of work essentially just trying to modulate 3D printed structures to again try to get differing mechanical properties and different biological effects you know within a construct, but using the same material essentially. And we both went through something called the ICOR program with.

These separate projects. So we went through it as separate investigators. But if you never heard of it, iCor was the National Science Foundation's adaptation of lean startup. So I think a lot of people have heard of lean startup. Essentially this idea, and again, this is not a new idea now, but 15 years ago, this was a groundbreaking idea, right? That startups shouldn't be built like big hierarchical organizations. They should be built like tiny cross-disciplinary teams.

And then you should force everybody to go out and talk in person to potential customers to validate a commercial hypothesis. both of us going through that program with these different projects essentially forced us to talk to surgeons and clinicians and and even in some cases patients who were suffering from cartilage damage and ostearthritis and joint pain, and really start to think a lot more critically about what's the practical problem, what is the clinical problem.

And I think we both kind of came to the conclusion that our existing technologies might be interesting science projects, but they weren't scalable. They probably actually weren't applicable in the real world. but it got us both really passionate about the mission statement, which is there has to be a better way to address cartilage damage in younger patients. So we both kind of returned to the lab. We both had a couple years, you know, left in our programs, but both sort of

Ben Holmes (07:12.71)
Had had that same problem, that clinical challenge, as well as the challenge that surgeons are having today with trying to adapt existing treatments and get good outcomes for their patients. I mean, this is why it's still considered a huge unmet need. You know, we both returned to the lab with the problem reframed in our mind and really grounded in reality. And so we started talking, well, just because the technologies we had probably aren't practical.

That doesn't mean we've given up on the problem. And so from that point forward, we we sort of started talking collaboratively about the things that we had both learned going through this customer discovery process. And that just kind of naturally segued into all of a sudden we're working together on trying to develop and identify technologies. And that was the point at which Nathan identified the the chondrograft material. So basically the the nylon-based synthetic polymer composite that.

We 3D print into the chondrograft implant. Nathan started working with nylons and and some other really, I would say, really exotic untested materials in sort of like the orthopedics, orthobiologic space. and he was getting really, really nice results with this nylon nanomaterial, at least in terms of 3D printing fidelity, and also in scale. And so that kind of made him think: well, this material.

Which at least when I'm working with it feels and behaves like cartilage tissue, but it's really easy to 3D print it into a bioactive matrix. and it's also 3D printable in a way that you could actually scale. Like we can do like a hundred devices in a lot of 3D printing. So a lot of people think of 3D printing as very bespoke and and something you use for one-off. But we found this opportunity to say, hey, 3D printing is how we create the bioactive structure that the body likes to grow into, but we can scale it.

And actually produce these devices in in some realistic volume and make it easy to distribute the product to the surgeons. And so he did a really nice in vitro study that got published, you know, kind of looking at at basic cellular response and, you know, sort of looking at the early markers of tissue formation. And so he said, hey, you know, I think this would be a really good candidate for material for if we actually were serious about.

Jesus Moreno (09:08.727)
Mm-hmm.

Ben Holmes (09:35.367)
doing a startup and at this point we were about a year away from our graduating from our PhDs because we both gradu you know started at the same time, graduated around around the same time. And so at this point we really were starting to talk seriously about, hey, do we actually want to do a startup? And he said, Hey, you know, I think this material has a lot of potential. And so I said, well, you know, give me give me some of it and you know, I'll do a quick some quick experiments just kind of on my own time.

So, you know, I I 3D printed out some, you know, little test wafers, kind of had the initial same reaction. I was like, wow, this is way easier to 3D print than anything I've been working with over f the last five years of my PhD program. And then at at the time, you know, I was really doing a lot of microvascular work. So not cartilage cells specifically, but I I was doing a lot of research trying to, you know, 3D print structures and then coat them with molecules or coat them with something biologic and try to get microvascular

Cells to attach to to them and grow. And, you know, it was kind of getting mediocre results. So I was like, okay, I I think this would be a really good stress test for this material because that's one of the big challenges with chondrocytes as well, is actually getting them to adhere to materials in the first place, let alone grow anything. and you know, these these umbilical vascular cells that that I've been working with kind of had the same issue. It it was hard to get them to entice.

Hard to entice them to attach to materials in the first place, let alone grow anything. So I was like, okay, I'm gonna do like a 48 hour experiment. I'm gonna I'm gonna drop some of these cells onto these little 3D printed chondrograph wafers. I'm just gonna see what happens. And you know, ran the f ran the experiment for, you know, basically kept them in an incubator for 48 hours, did some staining and then and then went to go do some microscopy. And you know, what what I saw.

blew me away. you basically saw not just cell attachment, but the cells were starting to grow along the nanostructure and also grow along the the microstructure that was 3D printed. So there's there's two structures. There's the nanostructure to the material, there's the microstructure that's 3D printed, and saw the cells growing along and interacting with both these structures just within forty eight hours of culture. So you know that's we knew we we really had something.

Ben Holmes (11:56.309)
and that and that this was kind of the technology that we really wanted to pursue. and so from there, we founded the company, I think literally a week after I graduated, 'cause I I graduated first, a couple months ahead of Nathan. So within a within a week of me graduating, we went down to a lawyer's office, you know, here in downtown Washington, DC, you know, formed the original company, and you know, that was ten years ago now. So you know,

Jesus Moreno (12:11.863)
Yeah.

Ben Holmes (12:24.7)
Sure, we'll get into all the steps along the way, but that's really sort of the you know, that's sort of the genesis story of NanoCon.

Jesus Moreno (12:32.767)
And and one it's wonderful to hear how that reframing of the problem and that rush with reality focused both of you onto the same same area and brought about this this device, this breakthrough. and I also hear in in this r response how the academic

sphere is is very much part of the company how it clearly shaped how you built the company from day one and you founded nanocon in in 2016 and deliberately stayed in this DC to keep that research tied to George Washington and and the children's national alive but

Ben Holmes (13:29.148)
Yeah.

Jesus Moreno (13:30.449)
you've you've had ten years of let's say the the other side of that coin which is the commercial build, the commercial environment, the the now the entrepreneurial side of things. Looking back, how much of those early directions came from staying close to academia and is is there anything that you would do differently purely from a commercial point of view?

Ben Holmes (14:00.912)
Yeah, it's it's a great question and it's a it's a tough question. You know, I think to really put a finer point on it, why why did we want to stay close to academia? it really was for access to resources. You know, George Washington has been a a tremendous supporter of startups in general. and they actually have one of the top top ranked, nationally recognized sort of entrepreneurial academic environments now in in the country. So

It was access to continued technical resources because our our first major grant actually had our old had Grace's lab written in as a you know support partner. so it was a it was sort of a resource practicality, but also we continued to go through you know programs at the university. The university was was trying to build a stable of entrepreneurial and commercial advisors, not just

Scientific advisors that could could help startups and spin-outs kind of think about their business. So we wanted to be close to those resources. And then with the children's connection, it was really more of you know, that was our early clinical support. So, you know, that that project that we did at Children's came with funding. And it was actually a partnership with the orthopedic department, not with a you know academic or scientific lab. So

So in that case, when you say academia, I mean, really it was academic clinical research. You know, it was a it was a preclinical project. It was basically how we did our translational animal study was through that partnership, but it was partnership with a clinician, not partnership with a professor. you know, I'll say too, what's kept us in the area has really not been an academic tie. And I think that, you know, in our case.

The reason we've been here so long was it was sort of just right place, right time. I think, you know, if you go all the way down to Virginia, to Virginia Tech and Charlottesville, and you go all the way up through DC and go all the way up to Baltimore, where you've got University of May you you've got University of Maryland along the way, but you've also got Hopkins up in Baltimore. I mean, that's really kind of anchored a whole corridor of aspiring innovators and and aspiring entrepreneurs. And so I think that, you know, we really we really have been at kind of the epicenter of that ecosystem.

Ben Holmes (16:24.79)
you know, which is really the what we call the DMV. So it stands for the District Maryland at Virginia. We couldn't call it the tri-state area because that was already taken. but you know the DMV really is the epicenter and sort of the connection point between this this kind of mid-Atlantic network of you know research and technology and entrepreneurship. And the stuff that's kept us here has just been the growing and changing resources that are available.

Jesus Moreno (16:34.274)
Mm-hmm.

Ben Holmes (16:51.01)
you know, originally we were thinking of moving the company to New York or Boston to be part of the Johnson and Johnson incubator network J Labs. we had applied and gotten accepted. And then in the interim, when we were trying to raise the funding to support expansion, J Labs actually opened a like location here in Washington, DC. So then we moved into the DC location you know, instead of moving to a different city.

you know, fast forward to today, we we currently manufacture the device in in a facility called the Launchport in Baltimore, Maryland. and again, you know, we were looking for a new manufacturing partner, especially as we were moving towards clinical, you know, needing parts that were of the you know the right quality and the right validation and verification to actually go into human bodies, and then also preparing for a ramp to support.

the larger clinical trial as well as commercialization in the next couple of years. And so we were looking at places again all around the country. We were looking at Indiana. We were looking at you know, Chicago, Minneapolis, you know, looking in the Southwest, and you know, got connected with this group in Baltimore that was very specifically, you know, doing sort of like a growth stage, scale stage service for medical devices specifically. so again, I think it was sort of just like

Right place, right time. This is the right time to be doing med tech in this area. And the resources and the capacity and the capabilities are sort of growing and evolving along with our company, which has been a really interesting experience. And so I I would say, you know, I would say to anybody who's thinking of a a place to set up a base of operations, you know, Baltimore, sort of the DC area, you know, central and northern Virginia.

are great places to be doing med tech right now because there's a lot of capacity, there's a lot of space, there's a lot of talent, and there's starting to be real serious opportunities for funding. And I think that that's the thing that anyone who's listening to this is probably thinking about most, right? Is how am I going to fund my project? especially the state of Maryland, and Virginia has great programs too, but you know, both Virginia and Maryland have venture funds.

Ben Holmes (19:06.566)
You know, we actually are a portfolio company of TEDCo, which is the Maryland venture fund. So this is this is state money, taxpayer money that's used to fund venture investments. And we're in a we are a portfolio company of of that. And then also there there's a lot of non dilutive opportunities as well. And so you you mentioned that you know p piece of our funding over the years has been non dilutive. We actually got a rather large

grant from a program in Maryland called the Maryland Stem Cell Research Fund for manufacturing assistance. So again, it was kind of like right place, right time. We're ready to scale manufacturing, ready to move into, you know, real facility, do this in a controlled environment, have a quality process in place. Maryland just happens to have a you know very large funding opportunity to do this in their state. and Virginia has programs like this as well. So you know again, I I think that

The thing that's really kept us in the area, back to your point, it's not it's not just because that's where the university we spun out of was. That was true for probably the first couple of years, but we were always looking and willing to move. It just so happened that, you know, whenever we were getting to the next stage of growth, this area had the resources that we we needed at the time and and kept us here in the ecosystem.

Jesus Moreno (20:31.241)
Well, that's certainly a blessing to to had found that ecosystem and and being in the right place at the right time. but in and hopefully not in too too harsh of a contrast, you're running your first inhuman in Panama. and you're s you you point you pointed to OUS as streamlined

Ben Holmes (20:41.084)
Mm-hmm.

Ben Holmes (20:51.362)
huh.

Jesus Moreno (21:01.569)
opportunity to to get clinical data because there's a lower regulatory let's say bar to clear or less friction in the regulatory process stronger a strong not not necessarily stronger but strong clinical ecosystem as as reasons to look to other regions

Ben Holmes (21:03.984)
Mm-hmm.

Jesus Moreno (21:29.655)
Five years ago, most orthopedic devices wouldn't have looked at Latin America with with that lens. So to from your perspective, from your experience, what actually changed on the regulatory side or in the traditional market to make this the smart move in twenty twenty six?

Ben Holmes (21:55.217)
Yeah, absolutely. And and I I appreciate the way you framed that because, you know, we've been thinking about clinical for the last five years. And when we s when we first started thinking seriously about where are we gonna do this first, you're absolutely right. We were not considering Latin America at all. And you even named some of the places we considered up top. you places like Eastern Europe, places like Australia. but I but I think, you know, why why Latin America and why now? You know, it's it's

Places like Panama and some other countries as well have been very smart about elevating the clinical standard of care, elevating the clinical practice, and at the hospital level being able to participate in high quality research. And when I say high quality, I mean conducting trials in a way with a level of documentation and documentation control.

That can be ported over to the FDA. Because I think historically that's actually the big problem. It's not that places have bad doctors or bad standard of care. It's that they're not able to collect the data and run the trial in a way that the FDA is comfortable with the compliance and comfortable with the quality of the documented data. And I think that's a very different skill set and a very different operational, I'll say, capacity or an operational ability than just running good clinical care, right? And so I think that just

you know, to back it up and and approach this at a high level, you have to have high quality standard of care that, you know, matches what's done in the West. you have to have, to your point, a a streamlined regulatory process. But also I think I think a process where you do have high quality and quality control, but it's put on the hospital and it's not dependent on the regulatory process. Because at least in Panama,

You know, we we from start to finish, I think it took us about six or seven weeks to get both Ministry of Health approval as well as the ethics approval from the hospital, because they have a harmonized process where you sort of start with the regulatory body, but then the regulatory body sort of hands it over and defers to the ethics, and then they come back together at the end and sort of like in a harmonized way grant the approval, which is a very smart way to do it. but at least in our experience so far, it means that you know, the hospital

Ben Holmes (24:20.298)
or the clinic has the the level of control to ensure that this is going to be a high quality study, high quality data that the FDA will accept, but doesn't default to the regulatory scheme to create that hurt that burden or that hurdle, which, you know, in other places, you know, can be months or or, you know, even in Europe now, taking longer than it would take to get an FDA clearance to start a trial. So I I think it's very smart and that's why it's fast.

But at the same time, I mean the the clinic that we're working out out of and that we've we've stood up as a as a study site is fantastic. The s the surgeons, you know, basically do the same things that at least a US surgeon does to treat the sa the same patient population. so I think there's also considerations about what is the surgical practice and what does what do the demographics look like. you know, the the

Development of the earlier stage cartilage injuries, it's you know as common or on par with what it is here. The injuries themselves you know look very similar to what's being diagnosed and treated in the US. So it's there's also an important piece as well, you know, in terms of what is the population experiencing from a health perspective. And does the population actually have this problem and need treatment? And so we we found at least in Panama that that was very much the case. You know, people are suffering from you know trauma and early arthritis.

related cartilage loss. It's happening at a similar rate. It's happening happening in a similar similar age of patient. and that and that the surgeons are, you know, just like here in the US, the the surgeons are hungry for a new solution to this problem. And so I think it it it does also go beyond just compliance or can you collect the data in a way that the FDA likes. It's it's we're actually addressing the same problem. We're just the problem's in Panama. It's not in the US. So I think that's also a really critical piece of it. And

You know, for anyone listening to this, whether it's in orthopedics or outside of orthopedics, I would say also that's how to pressure test is this the right opportunity? And I think, you know, what we've seen again, our experiences in Panama, but you know, people recommended other places in Latin America to us. and we're starting to look at that for our randomized trial, our future randomized trial. you know, it's it's are you can you address the same problem? Can you get the same patients? and I think that what's again, what's very interesting is Latin America

Ben Holmes (26:41.7)
you know, does seem to at least in orthopedics have a lot of the same issues that American patients are facing. So you know, I think for that reason too, it also makes it a great place to do studies like ours, because you can actually get the patients and you actually have the surgeons that you know can give you the level of feedback that is transferable to the US market. I'll say the other thing too that's great about it is communication is so critical with your

with your clinical sites. You know, we we and this is a note for the editorial people. We just treated the first patient, but I was telling Jesus I wanted to wait until we get the confirmation that their follow-up appointment did well. So that'll be later today and I'll send an email that this part can be released. So just a note for the editorial people. You know, we just treated the first patient on Thursday and we all went to the case. You know, this is the first case ever. This is incredibly exciting.

But also a lot can go wrong when no one's ever done this ever, except for some veterinary surgeons have done it in animals. A horse surgeon did it in horses. You know, a human surgeon has never done it in a live human being. So I was there. you know, my my senior clinical study director and my clinical program manager were both there, and the senior engineer who did the design work on our surgical tools was also there. So we had a big entourage.

you know, the clinical staff also had the entire staff there. So the entire OR nursing staff was there. The surgeon who was doing the case was there, but also his colleague who was also treating patients was there to observe and assist. You know, there were other people fr I think they probably were like twenty people in this room you know, surrounding this this yeah, exa exactly. No, really it felt it felt like it felt like watching felt like watching LeBron shoot a you know, three pointer.

Jesus Moreno (28:24.904)
No no pressure, right?

Ben Holmes (28:34.822)
you know, 10 seconds from the buzzer. It was it was a wild experience, honestly. but the point is, you know, we had a lot of people to coordinate. You know, my team is all over the country. We're not all here in D I'm the only one who's here in DC. so people were flying in from all over the country. We had one person fly down from Canada. and just one being able to coordinate with the people at the clinic in the weeks leading up to the case, you know, on a time zone that's only an hour off of ours.

is a big deal. That makes life so much easier. Like you don't until you live it, you know, you don't understand what a difference that is. And then also being able to coordinate all these people to fly there, you know, making it relatively easy. You know, again, Panama's not that far away. You know, the broader Latin America is not that far away from the US. you know, I think the longest the longest single flight somebody took was four hours. It was probably me, 'cause you can fly direct to a lot of places from DC. But

you know, I think just being able to provide the hands on support and the hands on oversight that the clinical sites need is really important. And it's it's hard to do that with Europe. It's really hard to do that with Asia or Australia. You know, it just makes life in order of magnitude more complicated. and if something goes wrong or if there's something that needs to be communicated in a timely fashion, which it hasn't happened to us yet.

but it just it just makes things more complicated. It creates more delays. and and so I think that's also something that it really can't be understated, you know, for for small and medium sized companies where execution and operation is so critical and something going wrong or something popping up that's unexpected, you know, it creates a it creates a roadblock that's an order of magnitude more challenging than it is for a large company. So

I I think also just as a resource, the fact that Latin America is right there. it just again makes it such an attractive opportunity.

Jesus Moreno (30:42.477)
And you can wrap that with a nice bow of it being a third of the cost, a fourth of the cost of doing a US trial. So it it it really really you know builds a strong case for for Latama as a a good destination for clinical research. and but again, in contrast to that.

Ben Holmes (30:49.724)
Yes. Yes.

Ben Holmes (31:04.998)
Mm-hmm.

Jesus Moreno (31:12.225)
You're running a trial also in Ontario, if if I'm not mistaken. And that in of itself, it's it's challenging for a company of your size, that's a real bet on operational bandwidth. what's the actual reasoning behind running two early feasibility studies in parallel, instead of banking everything on on one geography first and then focusing on on another one? And

Ben Holmes (31:16.305)
Uh-huh.

Jesus Moreno (31:42.121)
And what have been some of those cultural differences you've you've you know faced as as you run the trials?

Ben Holmes (31:49.713)
Yeah, absolutely. And and I think, you know, by the way, this is not uncommon. You know, one of one of my investors who is a prolific serial entrepreneur in the medical device space, actually one of the people who supported this move t to to doing work in Panama was in a similar situation to us with one of his former projects where they had gotten approval to do a first in human study in somewhere in Europe, I think Italy, if I'm remembering correctly, but in in Western Europe.

And it was just taking too long because of the the bureaucratic realities. you know, it took it was taking them a long time to get the CE mark, and they actually did get the CE mark or the the CE approval to do the study, not the mark. but they but they you they worked through a six-month process, I think, to get that. And then it was taking a really long time to get the ethics approval from the hospital. and then they were they were running into roadblocks with contracting.

This was exactly our same experience in Canada. It was just, it was just taking too long. and so, you know, th this story that he told me was rather than walk away from it, they said, okay, we need to quickly pivot to somet something else and see if we know let's see if we can not abandon it, but stand up another trial somewhere else. Because I think it always it always creates a strategic risk if you shut down a country. Because then you have to explain, well, why did you shut it down?

Even if it's a benign example like this, where it's like, well, just was taking too long and we need to we need to execute and we need to get the data and you know, there's other places that we can do it. So, you know, back to my investor story, they actually went to Columbia and they were able to get a trial stood up pretty quickly and they started to enroll patients and then the and then the Italian study sort of like fell in line and they ended up getting patients there as well. So fat you know, fast forward to what NanoCon is doing.

Same experience. You know, we we got an approval in Canada from Health from the Health Canada from their regulatory body about a year ago. And we started to work through the process with a clinical site, and it was taking a long time. And we got ethics approval, but then they weren't identifying patients very quickly, and then we were having some issues with the contract. And so it basically was the same same thing, just a lot of red tape.

Ben Holmes (34:12.048)
lot of bureaucracy, and and a lot of I'll say misalignment between the different stakeholders. so we had thought about Latin America briefly. And you know, early this year, you know, I kind of sat down with my team and said, hey, I think we can't keep waiting for Canada. This is taking way too long. so we kind of re-engaged with this clinical site in Panama City and the conversation spun up really quickly and then

You know, fast forward to today, we've initiated the site, we've gotten all the approvals, and editorial pause. We've treated the first patient. so but again, if you can treat patients in a different geography, it's worthwhile to do it because then it just adds an extra layer of confidence to your data. And again, sometimes these decisions are not purely for the FDA, you know, it's it's

for talking to investors, it's for talking to surgeons, like, hey, we did it in Panama in Canada. You know, similar positive result. That's kind of what we're hoping to get. but also it just helps a little bit with enrollment because you can have the potential to enroll faster rather than putting it all on one site or one geography. So again, we're sort of in the position because we already had the approval in Canada and we didn't want to just walk away from it.

And it would be nice to get some patients in a different geography to add a little bit of confidence to the daty data. But you know, also to your point, if I could go back in time and you know, do this a year ago in Panama, I would just do it. You know, you're right. I don't I don't think it adds enough value to intentionally say I'm gonna do two to very different geographies. It it just sort of happened that way. that we started one place, it was too slow, so then we started a second place and it's going quickly.

Jesus Moreno (35:59.637)
Mm-hmm. And and makes total sense not to, you know, bite the bullet as as they say, and and lose the time and effort invested in in that other region and then having to explain why it was shut down and and sh maybe casting a a shadow of a doubt on on the technology. but now

Ben Holmes (36:20.434)
Mm.

Jesus Moreno (36:24.669)
as as Latin America is positioning itself as as the go to, let's say, for for med tech, in your experience, and if other med tech companies follow the the the lead of nanocons into Latin America, what do you think might give out first? is it side capacity? Is it investor comfort with the data?

Or is the FDA ultimately you know aligned with with accepting information from this region as as part of the regulatory process? Is there another factor that might, you know, be the weak link in the chain of MedTech in that South America?

Ben Holmes (37:18.276)
Yeah, so I I think well, I I'll say this and this this kind of goes back to a the the research we did on trying to pick sp a place, right? Not every country in Latin America is created equally. And I think that, you know, that speaks to the the quality of the standard of care and the quality of the clinical research ability at the clinical level in each country.

I think that also speaks to the regulatory environment in each country. Like is it a f because there are countries that have great clinical standards and are very comfortable doing research, but have actually pretty bad regulatory schemes or challenging regulatory schemes. So, you know, I think that what the ch what in my opinion, what the biggest challenge will be will be capacity. It'll be like let's let's say, you know, in the next five years everybody stops doing this Australia stuff.

And everybody, you know, everybody's already flocking away from Europe because of the changes that have happened there. But let's say, like, yeah, Latin America emerges as the one of the the premier or one of the premier places to do early clinical research or even later clinical research, I think it'll be capacity, because I think people won't be able to go to every country, and they also won't be able to go to every clinic in every country. So you know, I think that might be the biggest challenge is just are the good, well-known sites with good reputations and histories with the FDA.

Are they going to get inundated? I could see that being a potential challenge. I think the other challenge, too, is you know, as things are shifting away from the EU and Western Europe because of the you know how the environment has shifted so much due to their regulatory changes, you know, people are now actively looking for these other places, but that also has meant you know, historically, globally,

virtually most countries in the world that aren't in Europe or or you know the US or Canada will it will accept an FDA or an EU approval as like a fast track or a rubber stamp into commercialization. but with the loss of EU as of the EU as sort of a reasonable pathway for commercial entry

Ben Holmes (39:39.911)
A lot of countries are now looking for ways to stand up their own, you know, regulatory schemes. And I think we're seeing that a lot in Latin America now, that, you know, countries will still a lot of countries will still accept an FDA approval, but they're also trying to set up their own approval processes. You know, one to respond to sort of that, you know, lag with stuff coming out of the EU, but I think also realizing that if they are a place that people are doing early clinical work.

They could also be a place where people could enter the market early, because I think I think you know, again, this has certainly been the feedback in Panama. so I won't speak to other countries, but the feedback we've gotten in Panama is that one of the motivations for doing this research is they want to get this stuff into the country and actually into general use early. So I actually think that that will not one, I could see I could see that being a challenge with capacity if that's another reason why people

want to flock to Latin America to do w research, but I could also see it being an incentive. and I could see it actually being a way that we alleviate the challenge of capacity. You know, if if more and more countries institute smart regulatory schemes, and then that gets more and more clinics on board with the research piece and provides that incentive for, hey, if we beef up our research capacity, if we actually invest in having research coordinators and research staff and those types of you know essential support roles, we actually get

you know, GCC certifications or do training, you know, there's an incentive because participating in the research gets you first in line and first at the door to actually bring this into clinical practice. So I I guess that's sort of a way to say, in my opinion, that could be a way to address this challenge of capacity to basically provide the incentive for clinics to put the investment in to be able to do it.

Jesus Moreno (41:34.453)
And as you pointed out, countries in Latin America, they're they're cannot be all put in the same container. They're they're very different. And exploring the region is nuanced and requires a partner, a strategic partner that that is familiar with those differences and understands you know the pros and cons of of each country. so before we we go through the

Ben Holmes (41:42.642)
Mm.

Ben Holmes (41:49.906)
Mm.

Jesus Moreno (42:04.531)
step by step or not the step by step, but the practicals of setting up the the clinical trial in Panama, which I'm very excited or or interested in in learning from you. I would like to hear a little bit about when when you were vetting that CRO and the site infrastructure, what actually mattered the most to you and and w where the providers you looked at

closely but ultimately didn't pass. What what were those, you know shall I'll say red flags or or derogatory marks that you identified and and why you chose to go a different way?

Ben Holmes (42:50.192)
Yeah, for sure. I mean I I think at the end of the day for us it was it was speed and experience. And so speed from the regulatory interaction side, because you know, I'll use Columbia as an example. you know, very great place to do research and it's actually a place where we're considering maybe doing pivotal work there, maybe considering, not promising or saying we're doing that.

But you know, it's a pla it's a place that you know has a lot of experience doing orthopedics, especially and within our indication. But what we always had heard was that the regulatory process was very slow. I think the estimate I got from from an experienced regulatory consultant there was like 180 days to go from filing to approval. and then also the you know, an ethics process that was not harmonized.

So, you know, you're looking at sort of like Western like time scales, and that was not going to make sense for us. So, you know, we were looking for places that had fast, low burden regulatory processes. So Panama certainly checks that box. But then at the same time, you know, it was really important to us that we're we wanted to do a study that would be admissible to the FDA. So then that meant, okay, we need clinics that one actually have experience doing research. So this isn't their first study.

Or this isn't like their second or third study. You know, they have done multiple studies, you know, multiple studies within orthopedics, you know, had well-trained surgeons as well, because one thing that you'll see a little bit outside the United States is like, you know, there's some places where they actually have, you know, sports medicine or soft tissue specialists. They don't just rely on the joint.

reconstruction people to like also do some cartilage defect filling. so it was important to us to have the right clinician profile. but then also, as I said, people that have participated in research and had a track record with the FDA. So the clinic we're working with actually has quite a lot of experience in doing these studies and doing them for FDA sub FDA submissions specifically. And then finally just making sure they have on in general, like if they've done all of that, this is

Ben Holmes (45:04.432)
you know, ninety nine point nine percent of the time this is also an easy box to check, but it's making sure they also have the right clinical support infrastructure. So I kind of touched on it earlier. you know, do they have a dedicated research coordinator? Do they have additional research support staff? You know, not a physician assistant or not OR techs or, you know, none of that. People that are there to specifically support the research activities. you know, which which

This this clinic as well as other clinics in Panama do. So it's it's really just they have a culture of doing research, they're motivated to do it. and also they actually have the physical infrastructure and the people to do high quality research. So those are all the things we looked for. It was can we get all of that and can we also get it fast? And at least in the case of Panama, that's what we have found is you can, you know, basic have it all.

Jesus Moreno (45:59.193)
And can you walk us a little bit or or shortly in through the timeline or the sequence of steps that you undertook to stand up the the trial, how long that took and you know, what were like key milestones along the way?

Ben Holmes (46:16.358)
Yeah, absolutely. So another night another nice thing is that this clinic actually had in house regulatory support. So we didn't actually have to bring in an outside consultant or, you know, a CRO, a traditional CRO to do the regulatory piece. That's very uncommon, I will say. so I think we were just that was just like a nice extra plus. on top of everything else. so save some additional money and time, but

You know, basically worked with their regulatory people, spent about two weeks putting together the package. so very similar to what you'd submit in other countries. So, you know, preclinical testing, testing reports, you know, the IFU, the the investigator brochure, the patient brochure, you know, we had a little bit of like targeted marketing stuff that usually has to go through e ethics. so all that all the stuff you'd have for a normal

package, but basically putting together the regulatory and the ethics package as one. then in Panama, you submit the regulatory piece 15 days ahead of the IRB. So that basically gives the regulators time to review everything and then and then provide their questions directly to the IRB. So that was done I think we got that in in like early April. And then the IRB meeting was in late April.

So the IRB met. they did have a couple questions. So then we had some back and forth on questions. and then it was about, you know, another two or three weeks, I think, for the IRB to convene another meeting. and then they basically approved it. And then they submitted that to the ministry. And then I think it was maybe like forty eight hours for the ministry to you know respond that they appro they have received it and approved. So when I say it's harmonized, that's what I mean by harmonized. and again, I think the whole process took about

I think it was about seven weeks to go from submission to that approval. But I think what is unique in Panama, and I'm sure this is probably true at other places, I'm just not well versed. but at least what's unique compared to US or Canada or places in Europe is that the process was so harmonized like that. It wasn't something where the sponsor was relying on talking to these separate pieces and bringing it together, which which is really nice and very smart.

Ben Holmes (48:40.58)
because it saves a lot of time. and I think also probably allows for better regulation and better ethics review if if those two people are working together to review something, rather than doing it separately and sponsors stuck in the middle.

Jesus Moreno (48:57.377)
You did you say that you didn't use a CRO at all? Or was the CRO not not involved in that?

Ben Holmes (49:00.708)
No, no, we did we yes, so we did not use a CRO. We actually have it we actually invested in in house clinical support. So I have a clinical study director and I and and then we also have a program director. now I I will say that that doesn't replace using a CRO in a randomized trial, because you need a lot of a lot of hands to support a large randomized trial, but that's the direction we decided to go for this first inhuman.

Just because we wanted a really, really high level of oversight and control. and also we were talking to a couple CROs about supporting Panama, but ultimately the the clinic that we ended up getting connected with, like I said, I think it's very unique that they have in house regulatory support. And so they basically said, like, you don't need a CRO, we do everything a CRO can do. And we'd kind of prefer that you not bring in a CRO. but again, I think that's unique.

I think that's very unique to this clinic that they invested in that capacity. I would say nine times out of ten, you probably need a Sierra to help you, especially with the regulatory piece, because we didn't understand that process at all. Like if the hospital had not picked that up, we didn't know how to do that. We didn't have Panama experience. So again, I think for us a very unique situation.

Jesus Moreno (50:21.569)
course. And on the other side of that the the flip side of the study is well FDA accepting the data and Condograft already carries FDA breakthrough device status and and health clearance in Canada. So Panama data has the has to feed into much larger packages downstream.

Ben Holmes (50:50.802)
Mm-hmm.

Jesus Moreno (50:51.437)
how are you making sure the data quality and monitoring standards stay consistent across Panama and Ontario so that the package holds together when when you submit it?

Ben Holmes (51:04.642)
Mm-hmm. Yeah. You know, I think the the nice thing is that we are we are actually working off of a protocol that the FDA reviewed and you know approved with some feedback. So not not approval to do work at the FDA, but the but the FDA did say, we we agree with your design of a first and human study. And we if you came back with data that this would give us the data we'd want to see from a safety perspective. So basically having that protocol set in stone.

And having that harmonized between the two clinical sites. And that also means patient screening, exclusion, and exclusion criteria, the follow-ups, the primary and secondary endpoints, that's all identical. And so again, that comes down to site selection. Are you going to a clinical site that has the right MRI, that has radiologists, you know, that has the clinical support staff that you can train to use an iPad to put in the patient data?

you know, having also having a you know electronic data database that we set up. So we set up and run a database that both the sites feed their data into as well. So not keeping things in country, not trying to gather things on paper, you know, and again, finding sites that have the people and have the willingness to interface with it you know, in EDS.

rather than just doing it on paper or just doing it locally and then sending us you know a file. so that's r that's really how you check compliance and and monitor. And then you you know again I think at this stage with a small number of patients and only two clinical sites, you know, having the people in-house or if we needed it having the support of a CRO to make sure people are staying compliant, that's how you do it. It's having people

But put their hands on the project and just check, make sure things are being done properly. but you know, it goes back to communication and documentation and you know, just just making sure you establish that early that like we're gonna be talking to you as the sponsor. Like we expect a response. A lot of this has to be documented. also having training. So I mean, we did on-site what's called a s a site initiation visit. so actually having our clinical people and like a CRO would do this.

Ben Holmes (53:30.17)
or in our case, our people did this, but you know, having them actually go on-site, conduct an in-person training w on how to capture the data, how to identify the patients, how to do the follow-ups. you know, it goes beyond just training the surgeon into how to do the procedure. It's it's also training the staff in how to participate in the clinical trial. So that's also really, really critical, that education piece of it.

Jesus Moreno (53:56.595)
Understood. So yeah, being an early adopter of structure allows those those institutions to better serve their sponsors. and and keeping a consistent consistent pipeline for for the clinical data that has been previously approved by the the targeted

Ben Holmes (54:08.796)
Yes, a hundred percent.

Jesus Moreno (54:24.487)
regulator FDA in this case. I think all those elements need to be lined up before executing. and that's that's great insight. Thank you for that, Ben. now zooming out, taking a step back, if this first inhuman data reads out the way you're hoping, what does the next 18 months look like for Condograd and NanoCon? how

Ben Holmes (54:27.026)
Mm.

Ben Holmes (54:52.146)
Yeah.

Jesus Moreno (54:53.397)
What are the next steps? What is exciting about the pipeline?

Ben Holmes (54:56.338)
Yeah, I mean, I think the next big step is then gonna be taking that data and raising the money to keep the company going and and do the next big project, which will be the randomized trial, right? So you know, the next six months looks like enrolling the rest of those patients, so ten patients, and starting to collect the early clinical d data points. So in this study, we're doing a six week follow up.

A three-month follow-up, a six-month follow-up, and a 12-month follow-up. you know, by the end of this year, we will have you know, all the pay all 10 patients enrolled, and we will start to have, you know, we'll have the six-week data from everybody and then hopefully we'll have the three month data from most people. And then by early next year, we'll have the six month data, and that's kind of the first trigger for starting to talk to regulators. So, you know, we plan to go to Health Canada.

We plan to go to FDA and then we also plan to and we're still trying to flesh this out ourselves, but you know, the the experience so far in Panama has been so positive and we assume it'll continue to be positive that you know we also want to consider Panama and some other Latin American sites as as randomized trial participants. And so that six month data is really the the first real significant safety endpoint. So that's when that discussion starts.

you can also think about the funding happening in parallel to that. And so I think if everything lines up correctly, you know, we'll have that funding closed you know, in the second half of next year. we'll also start to have some of those regulatory approvals in the second half of next year, and we could be starting to treat patients, you know, I'll say aggressively speaking, you know, beginning of Q four of next year, you know, could be starting.

those first clinical sites where wherever they are in the world, right? Maybe that's in the US, maybe that's in Panama, maybe that's in Canada, maybe that's some combination. but that's that's really how we're looking to stage things. and and that's the trajectory we're trying to keep things on.

Jesus Moreno (57:09.387)
Very exciting, Ben. Ben, thank you so much for for sharing with us all of this insight and all this steps in your journey. And I think the through through line today is simple, clear, but but highly relevant. It it's about getting first in human data from a breakthrough device to l let me let me restate that.

I think the through through line today is simple. Getting first in human data from a breakthrough device doesn't require waiting on a traditional market to catch up. It it what it actually requires is knowing exactly which regulatory doors are open and where the opportunity lies, as you've expressed and and shown proof for.

Latin America seems to be a prime example of that and having the operational discipline to execute according to plan are keys to success in in in this region and the market in general, given how how the traditional geographies are are behaving currently. So thank you for for this insight. I hope

our audience can incorporate this this hard and costly lessons and that it results in, you know, the tie rising and all boats rising with it.

Ben Holmes (58:54.482)
Mm-hmm. Absolutely. Very well said. And you know, again, I'm happy that I could be an example to anyone listening and wanting to learn more about you know, this topic of clinical research. I, you know, you don't have to tell me what a challenge it is to, you know, kind of cross that threshold into the clinical world. And and I just hope that I provided some helpful information to people that are looking to learn more about it. So thanks again for having me on. It really was a pleasure.

Jesus Moreno (59:21.901)
Thank you, Ben and absolutely that's that's exactly what we're here for. to our audience, thank you for tuning in to Global Trial Accelerators. If this episode challenged you and how you think about where to run first in human trials, share it with a colleague or maybe a clinician that needs to hear it. Please consider subscribing and until next time, keep accelerating.