First-in-Human Clinical Trials in Latin America, What MedTech Teams Need to Know Before They Expand

Okay.

And make me co-host.

Yeah, in a second. I do not see him. Jose, if you're in the… or Julio, if you're in the waiting room, please raise your hand. Paneless. I'm gonna just send him the link again. P. Coast… Confirm. Co-host. Okay, now I'm going back to… assume…

Sorry for the confusion, folks. Just…

We didn't start it yet, right?

It started. Tesions… Edit. Julio, resend. Okay, I've sent him the… Megan…

Hi, Andre.

Bongiorno.

Yeah, Buena Sera. We're in… we're in Portugal right now.

Oh, really? Okay, great.

Julio, if you're online, please raise your hand. Hello? Okay, so, we're having a minor tech… well, we're having a technical difficulty at the moment, with getting the speaker connected, working on that. Please bear with me.

Mmm. I'm also traveling in Portugal, for… reps… Euroconvergence, which just finished a half an hour ago. It was an exciting event. It was, even bigger than last year, and There were… there were a lot of good sessions, a lot of good speakers, and, Yeah, it went… it went really well. While we're… Trying to figure this out. Show. Many of you have seen the…

the MLV100 voting is up. In case you're, not on the list or, know somebody that should be on the list, please go to mlv.ai slash mlv100, and vote for your favorites, or nominate new ones. Surprisingly, in the last… 24 hours, we've had, like, 3,000 votes. Pour in, and and more than 100 new nominations, so it's encouraging to see the people, participating in this and, in sharing it so, so widely. If you see the MLV posts, please feel free to repost them.

From anybody that puts them up, and… and show your support, because that's… Really important. I am… Still having trouble, yeah, JK… She knows. I apologize for this, show, next Friday. We're going to be talking about QMS… system and, the conversation your clients are quietly having without you. This session is particularly useful for consultants.

Because, the provider is really looking to partner with consultants who have clients who need a QMS, so that's a… a good thing to attend. If you're a consultant, there's… It'll be a valuable… thing for you, I hope. I… so, this is completely my fault. I, am in Portugal right now, and it's a 5-hour time difference, and am jet-lagged, and… having… Problems with…

Mmm… Connecting the speakers, so I'm texting with him on… LinkedIn at the moment. I need to… copy the link… Mmm… Again, I apologize for this, but I'm… I'm really a little bit… Bewildered at the moment. Copy invite link. 2…

Hmm. In the meantime, does anyone have any announcements that they would like to make?

It's Friday!

Thank you. Thanks. For saving me. Yeah… Yikes. Okay, well, I just sent him another link that hopefully will work. If not, we're gonna be… Going in a completely different direction.

Hey, Sean, if I could comment.

Yes.

you know, that graphic you sent out for the MLV100, with everyone's individual photo, they're throughout my entire feed, so you're getting a lot of coverage on LinkedIn.

That's great.

Yeah.

I like that. Thank you very much. I appreciate it. This is… HIJ… Yes, actually, Paul, everyone is invited to join, and speak. If you would like to be promoted, to panelist, please do so. This is a… A interactive webinar, and everyone, all of you who are attending are, just raise your hand if you'd like to be promoted to speaker.

And you can… Join in the conversation. I… really don't know what's going on. I'm gonna mute my audio for a moment.

How's everybody's Friday going? I'm a little tired today. Has anybody else found that… how is everybody's client loads working? I kind of like… it's like feast or famine right now out there in the industry.

Yeah, I would agree. It's definitely…

You know?

from across the pond. I think, there's a lot of companies waiting on this whole thing to pan out with the MDR revision, and they're holding out, and they're supposed to get… reach the deadline, but they're ignoring it, and I've been told that by customers that they're high-level management. You know, even though there's deadlines, they don't care. So everybody's sort of, I don't know, sleeping on it.

Yeah, I would agree. Well, I also find that people are having problems funding-wise, finding people who want to invest as well. It's like… it's like everybody's holding their breath, waiting to see, you know, what's gonna pan out.

Yeah, actually, I was at the RICA meeting, that is an EU-sponsored event of investors and companies and stuff in Basel, Switzerland, and they were saying, we are in an economic downturn. And investment's really tough right now. So, there was a number of startups there as well, from many different countries. And, so the overall… Atmosphere was sort of dampened, for lack of a better expression.

Well, our speaker is here. I owe him a sincere apology. I'm so sorry for the confusion. All I can say is jet lag and 5-hour time difference.

No worries, that happens.

I appreciate everybody's patience, with me today, and I'm gonna, turn it over to Julio. Today, we're here to talk about, first in human clinical trials in Latin America, which is a topic that I'm excited about, because it's not one that I've ever heard before.

Tell us, buddy?

Tell us about you.

Well, I've never heard about that topic when I started my… My venture in the clinical trial… world, more specifically, the first human world. I was born and raised in Colombia, as you can probably tell by my funny accent, and I moved to the States about 40 or something years ago. And my brother, Pedro, is a physician, my father was also a physician, and we left Colombia for Obvious reasons are around the 90s. And, you know, the Pablo Escobar and the guerrilla era of Colombia. And Pedro is really the genesis of what we do today, and Pedro trained at Harvard, at the Beth Israel Medical Center in Boston.

It's an interventional cardiologist. And, he became a professor at the University of Miami. And he met his mentor, who is Dr. Willem O'Neill, who is considered one of the top authorities in the world of interventional cardiology. And they both collaborated for many years, and they published, many papers, they issued a lot of, I mean, they were granted a lot of patents. wrote book chapters, I mean, many accomplishments in the interventional cardiology world. And that led them to advise medical device startups, U.S. medical device startups, in the cardiovascular space.

Meaning that, no harm. familiar the audience is with this world, but, medical innovation usually happens inside universities, inside labs. And these labs produce the intellectual property that gets translated into molecules, into medical devices, or medical technologies. And universities license that intellectual property out to third parties. Entrepreneurs, people who identify the potential of the medical technologies, and then they start companies based on those Intellectual property, or patents. So, that's who we deal with. I mean, small companies, setup companies, usually companies from Boston, usually companies from Minneapolis.

San Francisco, San Diego, and a few other places in the US. And they raise funds. They raise about… 3 to 5 million dollars, different rounds. Sometimes up to 10, 20, depending on the complexity of the technology. Of course, the more complex, the higher the risk, the more money you have to raise, and the longer it takes to get the technology to the market, or to humans. And, they build teams where they… hire the best people in the world that are experts at these type of technologies, and they start the development of these innovations. And part of that team is…

people like Pedro, my brother. people like Dr. William O'Neill, experts in interventional cardiology in their specific case, or experts in whatever therapeutic area they're working on, and they get these individuals to advise them on how to develop, how to do the animal testing. to do the human testing, etc. And that's really the genesis of what we do, who we are. I said, we started inside the University of Miami because Pedro, my brother, and Dr. O'Neill were professors of the university, and they were advising these medical device startups. with their cardiovascular devices, and they travel around the world, doing trials, nursing Emma trials for these companies. And they realized that there was really nobody in the world

Who was specifically dedicated to helping these startup companies with their first inhuman trials overseas. Meaning that if you are going to venture into a clinical trial overseas, there are many obstacles. to overcome, right? Imagine, it's a different country, different regulations, different, Patient profiles, a different hospital systems, a different way of doing business, cultural, differences, etc, etc. So… So, so…

So why go overseas? Why go overseas?

Well… Great question. In the U.S, First of all, the obvious reason is cost, right? That's the obvious, exactly. It's really expensive to do any healthcare-related procedure in the United States, as we all know. The not-so-obvious reason is patient recruitment. pension recruitment. It's a lot easier. faster to recruit patients overseas, for reasons I can get into in a minute. But there's another reason, which is the FDA. The bureaucracy of the FDA, the red tape at the FDA level for many Reasons as well. politics, turnover, many, many, many factors, but it's just difficult. There's another reason in the U.S, which is the size of the hospital systems. Imagine if you're a small startup.

Three people. A couple of million dollars in the bank. And you approach John Hopkins in Baltimore, or some Harvard lab in the, in, in, in Boston. And, you… you tried to get a meeting with them. They… they… they have… $20 million. that they just received from the NIH for a grant, for a… to do some research, and you are approaching this lab for a small trial, 5 patients, and you're just gonna pay the $500,000. So, it's difficult to compete with the level of money that gets funneled through labs in the United States. So, if you're a setup, they don't pay attention to you.

That much. You have to go overseas. So there are, like, 5 different reasons why companies go overseas.

That's great. So… We're talking about first-in-human trials. What differentiates first-in-human trials from Other trials, later stage trials, you know, and since we're talking about small startups, we're talking about interventional cardiology and related technologies, but, you know, definitely implantable devices. You know, what, what differentiates First Inhuman?

Yes. Well, we… the work that we do now, just to… clarify involves cardiology and other areas, other therapeutic areas, because organically, we have grown into ophthalmology, neurology. Orthopedics, et cetera, et cetera. So, the need is everywhere in the spectrum. It's all type of therapeutic areas. All type of setups in all therapeutic areas have this need. we mostly work on devices, but also applies to molecules. But it's a little different with molecules, but also applies to molecules. Anyway, so… The, the, the, one of the reasons why these companies go overseas is…

The fact that the healthcare system in these countries do not work, It says on paper. So it's really, really… it's just challenging for these companies to stay in the United States, and they do their first human trial in Latin America, in Eastern Europe, in Australia, in New Zealand. And they come back to the United States, and they do a larger study in the United States, because the FDA demands that. But I just want to make sure we all understand that cycle. And before I address your question, I also want to make sure we all understand the purpose of these companies. The purpose of these companies is not to sell the device in the United States.

It's not to sell a device anywhere in the world, which is weird, right? So what's the purpose of these companies? So the purpose of these companies is to get bought, to get acquired. by Boston Scientific. By Johnson & Johnson. By, you know, a big player. Medtronic, for example. So that's…

They're not actually trying to go to market, they're not trying.

Exactly. No.

Well, they.

No, no.

of efficacy to a larger manufacturer for acquisition purposes.

Exactly. Exactly.

Exactly.

Okay, so the…

me on that, yeah?

Yeah, so the business of the entrepreneurs, of the two or three entrepreneurs who license the technology from the university. is to sell the company, not to sell the individual devices, right? Not to set up commercialization or distribution networks all over the world. That's not where the money is for them. But that will take them 20 years. to replicate what Medtronic and Bossertifica have already developed over 200 years around the world, right? So… Going back to your question, Sean. The… the… the later… later phases… It's just different. I mean, because the riskier phases are the first phases. Phase 1, phase… Phase 2A, those are the riskier phases, and those are the phases that usually go overseas.

When the… the… when… because the job of the… entrepreneur. who licenses the technology to the university into their risk, the investment, the buyer. The reason why Medtronic pays $500 million for a startup company. It's because they don't wanna take the risk. Because there's a lot of risk. I mean, many of these companies fail. Most of them fail.

Hmm.

So Medtronic is not in the business of trial and error. They generally are in the business like Facebook, like Meta, like Google, like Apple. They are not in the innovation business, they're in the business of buying startup companies with the risk. the job of trying something in the market, and once they see that there's… that these companies already tested the waters, and they're… they have some traction, then they buy them, and incorporate them into their portfolio.

Okay. So, years ago, I… a mentor of mine in the medical device industry said to me, the difference between pharma and device industry, Sean, you have to understand, is that The medical device industry is largely incremental improvements on existing technology, that are bought through acquisition by the larger manufacturers. And whereas pharma is all about R&D, 15-year R&D cycles, developing molecules from, you know, nothing up to, you know, and bringing them to market. With that in mind, so what we're talking about here is largely different than what a lot of the people on the call deal with, which is working.

with…

small to medium enterprises, and taking them through the 510K process, taking them. CMA process, and then the commercialization process, and all of the risks attendant with that. So, now we're dealing with a completely different set of risks and challenges. So, when we, talk about taking clinical trials overseas, what are the things that most people in this room probably don't know? About the, you know, particular challenges, what to look for, what to look out for, and, and where they should go. Should they go to Latin America? Should they go to Eastern Europe? Should they go to India? I have no idea.

Yeah, the second question, I think, is a good introduction to the first answer. Boom. Well, there are options, of course. So… Years ago, companies we're going to Eastern Europe a lot, to Poland. Czech Republic, Georgia. And, about 22 years ago. And then things started changing in the UA… in the European Union. As you all know, things have evolved in the bloc. And, one of the things that is happening in the blog is that there…

Incorporating more and more countries, little by little. And they're going east. More and more towards… towards east. So… There are less and less countries to choose from. In Europe. That's one thing. So now, companies are going even more east. They're going to Asia. They're going to Kazakhstan. Can I even pronounce the name? So complicated. Kazakhstan, Afghanistan, countries like that, because They're being pushed. towards the east, more and more and more. And that's one thing. And the other thing is that the European Union changed the regulation.

I'm not sure if the audience, knows the difference between the, the… the MDR… the MDD.

Oh yeah, they're very familiar with the…

Exactly, okay, exactly. So, so the, the, the, the MDR… Really made a big, push for setup companies to look elsewhere. And that elsewhere is… Australia, New Zealand, And, more recently, Latin America. Because the business is like water. It's always… it flows and always tries to find the path of least resistance, right? So if it's difficult to do trials in Europe, difficult, expensive. etc, then it goes somewhere else. So, that's why they go to places like Latin America, because it's just easier, faster, and cheaper.

Yeah. So, would you like me to answer the question, your original question, or not? Yes.

Yes, please.

Okay, well, things to look out for. Obvious things. For example, I mean, cultural differences, many, many cultural differences. Even though Mexico is in the same hemisphere, Mexico is a different world from the United States, right? Even though it's in our backyard. imagine going to Chile, imagine going to Paraguay, imagine going to Argentina, it's even… more extreme, the cultural differences. Even within Latin America, we all speak the same language, we all have the same Catholic background, the same Spanish background. including Brazil, we share a lot of heritage together, we are totally different. I mean, a guy or a person from Venezuela is not the same as a person from Colombia or Panama, and they are in the same, you know, the same area. So…

So you have to look for those. So that's why having local help People who can't… Firstly. the cultural differences is really, really useful. And also, Latin America, or countries overseas. Very fragmented in regards to regulation. let's go back to Latin America. Latin America has over 30 countries. 33 to be specific. Every country has a different medical device regulation, or pharmaceutical regulation. So imagine, you're trying to navigate The waters of all these countries and trying to understand the different regulations, so it gets really confusing. So, the other thing is costumes. I mean, trying to import devices into these countries, because one thing is the actual regulatory

laws… for pharmaceuticals, for devices, the only thing is the costume laws. You don't want a product that got… to get stuck in costumes for… For months or years, because it defeats the purpose of going overseas if you want to do a fast clinical trial, right? So, things like that are… Some of the things that are… you have to look for. There are many more, but those are the main ones, I guess.

So one of the things that I'm having a little trouble understanding is then, you know, why would it be easier to get your clinical trial done in Latin America, than… For example, in Canada or in the United States, I mean, you… you mentioned the FDA and the regulatory requirements. Are there fewer requirements in these countries? Is it less strict? Is it…

Great question. Well, I alluded to a few reasons, economic reasons. pass reasons, meaning that it's really expensive to do calls in North America, Canada, United States. I mean, we all know that the healthcare system in the United States, particularly, is expensive. So, a, a procedure costs you $50,000 in the United States, which is not… unheard of. I mean, it's not uncommon. For a startup company, if I go to John Hopkins tomorrow to do a trial, it will probably cost me $50,000 for each patient. You can get the same… procedure done in Colombia, for example, For about $15,000, $20,000, $25,000.

I mean, so the cost savings are significant. Imagine if you're a startup company, 3 guys. a couple million dollars in the bank, you have 3 more years to go, so every penny counts. So that's one reason. The other reason is what I said. you knock on the door of these big hospital systems, big academic institutions in the United States, because in this country, we don't have small hospitals. We have big conflict. Because of the size of the country, because of the, the, the… Consolidation of the healthcare industry. Then, try to get a meeting. It will take you a month just to get a meeting with somebody who will tell you that you have to meet

another person. Two months later, and then that person tells you. similar thing. So the thing is, you're going to spend 3, 4, 5 months just planning the study at that hospital. What if you submit to the IRB, to the Institutional Review Board, and they say, no, after 6 months of meetings? It's just difficult to get investigators committed and get things done at these large hospitals because of the bureaucracy. Then you have the FDA. the FDA is extremely risk-averse. Extremely risk adverse. It makes sense. It's protecting the health of the Americans. That's fine. And you have another issue, which is… Patient recruitment.

Patient recruitment. In the U.S, people are busy, people have jobs. Access to healthcare is fairly simple. I mean, we all complain about the healthcare system in this country, but it's… it's just fantastic as compared to how it works in other countries, right? So, people have options here. People have access to the healthcare system here. You go to… to the ER, right now, and you're gonna get treated. Regardless of your economic level, of your socioeconomic status, you're gonna get treated. You can go to the best hospital in the United States right now, at the ER, you're gonna get treated. That doesn't happen overseas.

Overseas, in developing economies, Colombia, for example, when I was born and raised. I see people, when I go and visit my family, I go, and I… the pharmacy at the corner has a line that started at 5 again. People lining up to get a medication that was prescribed by the healthcare system. Because they cannot afford to pay for the medication out of pocket. They have to stay in line from 5 a.m. until 7 or 8, and they open the doors. And to see if they received the medication, to see if there is inventory. It's just difficult to have access to the healthcare system in these developing economies. So if you come, with…

A clinical trial, and you offer these to patients who have not receive… Treatment. for years. Then it's a… it's a… It's an easy sell, right? Patients want to be treated. People… patients want to be part of the healthcare system. People… I mean, patients want to be part of the trials, because the only… it's the only way into the system. You're gonna receive everything for free. They're gonna be treated with dignity. They're gonna get sent an Uber driver to pick them up, in the morning. 5 or 6 or 7 in the morning, with a family member, they're gonna be taken to the hospital. They're gonna be giving lunch, I mean, breakfast, lunch, and dinner. They're gonna get all the tests

Images, everything done. plus the procedure. And they're gonna also have all these follow-ups, everything for free. So they're really happy to participate in clinical trials. So, that in itself is a very compelling reason to go overseas.

I've worked with a number of contract research organizations, and I know that patient recruitment can be extremely difficult and challenging.

It is.

And, so it's interesting to hear this. You know, my question then would be, you know, which countries do you typically go to first? Let's say, I come to you with an investigational device, and I've decided, you know, I'd like to try it out, and let's say it's a cardio device, just for convenience sake. And it's developed with me and my university PhD friends, and we're… Yeah. …got the money, we got our two, three million dollars, and we're with you, and we said, great, we want to do a small first-in-human trial, 5-10 people, and… Where do we start in South America? Do we start in Colombia? Do we start in Chile? Do we start in Guatemala? I don't know, you know?

Yeah, it changes. When I started, working in this, industry, this space, Colombia was a top place. It's funny you mention it, but yeah, Colombia was the best country in Latin America for this type of work. then, there were some changes, political changes, and things like that, and then Colombia is no longer the best country for first-human work. Other countries have… Updated their regulations, and they have become more attractive. First of all, is it also, before I answer your question specifically, it's important to emphasize that countries around the world are competing Literally, competing for clinical trials, for clinical research.

Countries are competing, it's like the World Cup. Every country wants to host a World Cup, because it brings money and visitors, etc. It's exactly the same in clinical research. Functions are competing to attract foreign direct investment related to clinical research. Cubia, which is one of the top CROs in the world, as you all know, probably, issued a report, a couple years, a few years ago, and they… they were trying to measure the economic impact of a clinical trial in Latin America. And the conclusion of the report is that every… clinical trial that comes to a country in Latin America represents about $20,000 per patient, meaning that

every patient recruited in a clinical trial in Latin America represents an economic impact, direct economic impact, meaning the fee that goes to the hospital, to the investigator, to the stipend that the patient receives, the jobs, the salaries, everything. It's about $20,000. Imagine, I mean… if you have a country like Brazil. 250 million people, and a big percentage of the population are involved in clinical trials. is a direct economic impact. Not to mention. Not to mention big healthcare savings, but not… because all these functions, like in Canada, subsidies and government. aid, healthcare systems.

Every patient that participates in a clinical trial is one less patient that the government has to pay for, right? So… so countries are really, really competing for clinical research, so they are updating their laws. To make it easier. To make it, more predictable. to recruit, patients in, in, in, in, in, locally. So, to answer your question more specifically, right now. countries in Central America are really, really stepping up their game. It's an awesome place to do first human trials. Costa Rica, fantastic. El Salvador, out of all places, El Salvador is now the shining star. Dominican Republic is also a nice place. It's a Caribbean island, more than double the size of the countries that I just mentioned, individually.

Panama is about 5 million people, Costa Rica is a little more, Salvador is about 7, Dominican Republic is about 11. So… but it takes a little longer, so usually there's a correlation. The larger the country, the longer it takes to get approved. So I had to get a study approved in Brazil, or in Mexico, or in Argentina, or Colombia. The larger countries. It's gonna take you way more than in a smaller country. Meaning, In Panama. We have gotten, and this is a true story, you can look it up online, we got… there was a startup company out of Boston, Harvard Labs. Harvard University Labs. The company's called ASoft.

AXOFT. It made the news everywhere, because it was one of the first brain-computer interfaces. After the Neuralink. And we got approval for that trial, I think, in less than 60 days. There was another one. And this is a very high-risk device. Imagine a brain-computer interface. And then there was another one, a company out of Oxford University called Neurotex also made the news. We got approval in 15 days. Imagine a setup! I mean, the runway of the setup, how much money they save in the runway. By going to Panama, Costa Rica, Salvador. Versus Brazil… well, Brazil will probably… would have taken them 6, 8 months, or Argentina, or Mexico.

Oh, yeah.

So, one person writes in, in the chat, I have a de novo medical device, and I want to do first-in-man testing in Panama or Bolivia. Can you walk us through, step by step, how to do this? Do I need FDA approval? Do I need export approval? What requirements are required in-country, and how long does it take? I know that's very specific.

No, no, that's a perfect, question, to… to discuss the specifics of how these works. Well, first of all, we usually start with… executing an NDA with the company, with the setup, we received their the scope of the study. In other words, we received their protocol synopsis, which is usually a 3- to 5-page document that summarizes the scope of the study. We also received a site feasibility questionnaire. Right? The site feasibility Questionnaire is also a short document, probably 5 to 7 pages, where you ask, as the sponsor of the clinical trial, all the possible

Questions that you can think of to try to… Filter the good and the bad potential sites and investigators. So… it's like interviewing for a job, right? You set up a questionnaire, people answer, you screen them, and then they upload their resume. Same thing here. So then we start working our network. we've developed a network of over… I mean, for 20 years, many, many, many investigators, many hospitals all over Latin America, so we broadcast the opportunity, we get answers on the… on the questionnaire, we filter those answers, and we… come up with a handful of potential very good candidates. We… we meet with all of them, and then we select a potential site. Once we have that already selected, the site and the investigator and everything, then we do

The… filing, the submission. of the regulatory paperwork, meaning the dossier package. We take the company's documents, meaning the protocol, the investigator's brochure. the case report form, the patient report consent, the insurance policy, etc, letters here and there, and then we put everything together, we translate to the local language, mostly Spanish or Portuguese in the case of Brazil, then we submit. to the IRB, which is the Ethics Committee, Institutional Review Board, same thing to the IRB, which is usually a local committee, local entity within the hospital. It's external, but it's part of the

It's a committee that the hospital uses. To review and approve these type of studies. And then we get approval at the IRB, Don't answer our questions. Sometimes we present the studies, sometimes we don't. Regardless, we get approval. Once we get approval, depending on the country, you have to go to the national regulatory agency, like the equivalent of the FDA on those countries. The Ministry of Health. Usually it's at the Ministry of Health. Most countries, they need that, they want that. In a few countries, you don't have to do that. You just notify them that the IRB approved the study, and they are good to go, or we are good to go.

If we can officially omates this study. Meaning that we can officially Get an import permit to nationalize the investigation of products. You don't usually need an export permit from the United States. And of course, you don't need FDA approval, because the reason you're going overseas is to get clinical data for you to come back to the United States and get FDA approval. So, we're talking about investigational products, so the FDA doesn't get involved at all. They… they want to get involved. Once you've got… you have the data. you speak with the FDA, you speak with your investors to raise more funds.

for what's coming, which is a larger study in the United States, which is usually called the PIVOTA, or the Phase 3 study. The Pivotal study, which is a larger study. We're talking about 200, 300,000 patients versus 20 patients overseas. We're talking about 20 sites in the United States versus 1 or 2 sites overseas. And now we're talking about millions of dollars versus… $300, $500,000 overseas. But now, you also need to speak with your buyers, your potential buyers. That's when you pick up the phone and call Vectronic. Boston Scientific, Johnson & Johnson, and you tell them, hey, listen, I just did my first human in…

Am I? I guess… I just spoke with the FDA, my product works, you do an abide me. So you call all of them, and there's a bidding process for you, for your company, and that's how you make Your investors make a return, everybody's happy, and you move to the next company. And usually our clients are senior entrepreneurs, people who have done this many times. They probably have Done this 5 times. War.

Does anyone else on the call work with, clients that would be in the market for these kinds of services? Has anybody done this sort of thing? Does anybody have any experience with this, that they… that they can share with us, or… have any questions. I know one person had asked, you know, is the FDA gonna accept this, this clinical data? these kinds of data, whatever. You know, the, and… My understanding would be that this really… Is just the baseline for, the first… for the first studies, and so taking this investigational data to the FDA, sure, they'll look at it. Are they going to accept it and give you a 510K? No, they're not, you know?

Yeah, that's a… it's a different conversation.

You know, they want to see more studies, but this is to get your product off the ground, get the investors on board, and then hopefully just sell the technology without ever going through the commercialization process.

John, it's something to clarify here. The FDA has, for the purposes of the conversation, three different paths. Five ways. Regulatory pathways for approvals. for medical devices. The first one is the 510K pathway, the second one is the novel pathway, and the third one is the PMA pathway, which is the pre-market authorization pathway. Meaning that… With the 510K pathway, you don't really need clinical data. Because you have a predicate device. What you're doing is an incremental, very small incremental improvement over what other people have done in the past. that the FDA have approved to just show the FDA, listen, 20 other companies I've already…

work in this phase with this type of technology, you have approved them, I should get approval as well. And that's… that's the 510K. Then the double is when there is no predicate device, and then PMA. PMA is Class 3 devices, like high-risk implantable devices. So that's really what we're talking about here, PMA devices. high-risk devices.

I understand. Okay. So…

Can I just jump, jump in here really quick with a question, if I may? the countries that you're discussing, though, I mean, I'm a Canadian, I'm also Swiss, I've lived half my life in Switzerland, half my life in Canada, and in Canada, there's four seasons, right? In a lot of places in the United States, there's also four seasons, right? So, if you have, for example, a device that, delivers insulin, right? Then I think the seasonal conditions in which this device has to work also matters in the end, right? In a clinical study. So, and another big difference between Canada and Switzerland is that we have trains all over the place. You just jump on a train, you get to the next location. In Canada, you jump on a train, you have 24-hour delay to get into Toronto or Vancouver.

So, I mean, how do you deal with these? Because, I mean, these are environmental differences in the environment in which you're at, right? You have difference in seasons, you have difference in how you get to work, you know, and in Switzerland, a lot of people just jump the train. Canada, there's no way you're going to jump the train. Yeah, I'm just sort of curious on how you deal with these, I mean. in Canada, you have lots of ethnicities, a lot… I think, personally, a lot more than you have in Switzerland represented. Yeah. I'd be really interested in how you deal with these differences.

Welp… if I understand the question correctly, Stephanie, Latin America is very, very, very much urbanized. I think is… is… is one of the most urbanized areas of the world. If I understand your question correctly, People do not have to move that much in Latin America. Because we have… big, big cities, big cities. I mean, Mexico City… That's over 30 million people. You don't even find that in North America. I don't know why, but that's the way it is. The second largest city in Mexico, I think, is Guadalajara?

I mean, like, seven large cities. Anyway, the point is that we don't really have to deal with those Actors that you're describing, to be honest with you, in our studies, and also because our studies are small.

But, you know, when you deliver… but, you know, for me. I'm just looking at it at a global perspective. Yeah. I want to get… collect data that I can use in different jurisdictions, right? And these different jurisdictions may have four seasons in comparison to Latin America. In some regions, there's only two seasons. I mean, you have winter and summer, right? Or you just have summer. Oh, yeah.

That must have been something.

And then you have different environments in which you're working in it, and so when I set up a clinical study, then I want to have a region, actually, that best represents the working conditions of how this medical device, and what this medical device will be exposed to.

Yes.

In front with my question, yeah?

Yes, yes, yes. Now I understand the question more. Thank you for that clarification. But that applies on later phases. That doesn't necessarily apply on First Inhuman, at least for medical devices. Remember, medical devices, Or a hardware product. And the hardware product that has been developed for probably 3 years. 4, 5, sometimes 5 years, in a lab. And they have invested three, five million dollars on, on, on, on this product. On this, on this hardware. That has never been tested in humans. You've just completed 5… Pigs. your animal testing. It takes 5 sheep. That's usually the models that we see in our space.

So, you completed this animal testing, and you presumed That's gonna work in humans. Because you chose an animal model that is the closest one that you can get to. Before you get to humans. Not even Canaver's. work in this… in this space. Sometimes you can… kind of try with carnivores, but, you know, carnivores are just dead people, so they don't have blood circulation, things like that, so you really have to jump to humans. All you need is 5 patients, 10 patients, 15 patients. So you don't care if it is cold or hot, if it is snowing or raining. It's not a factor. You don't care if the patient has to come from 3 hours away from the hospital, you get the patient in, whatever it takes.

Yeah. It implanted.

Device on the patient.

One of the other, participants commented, what did he say? He said, the first in-human study is to get the ultra-risk-averse American doctors to begin to think about doing a study here in the U.S. Yes!

Great point!

You know…

point.

Before they'll do a study in Canada or in Switzerland, they'd really like to see it tried someplace else.

Yes.

Same with the United States. It's… it's… we… we… we don't… we don't want to assume that risk.

Yeah.

Somebody else assumed the risk.

Yeah.

And, you know, that brings up some interesting ethical discussions, but I'm not gonna go there.

I agree, yeah.

But I think what we're hearing is about an opportunity, for… inventors, people who are developing, Class 3 devices, implantable devices, that, that are new and different. And we're learning about a market, the university, people, and how they think about commercializing a product being very different from the 510K pathway and the… and, and even, U.S. FDA approval and, and, and MDR. That…

Seems to be 3 to 5 years down the road from the stage that we're at now, where we're talking about just getting the basic evidence in place to line up the investors, to find people that want to buy, that want to invest in the technology or purchase the technology outright.

Yes.

So, with that in mind, then, are your clients successful in, unloading their technology on, larger companies? You know, what kind of success rate do you see with.

Yes. First of all, before I get there, I want to point something out related to what you just mentioned about ethical questioning and things like that. I've been in this industry for about 20 years, and you'd be amazed How safe? These products are. Because the first… The first endpoint on… Endpoint, I assume everybody knows what an endpoint is. The first endpoint, usually the endpoint of the first human child is safety, not efficacy. You're not looking to see if the device works or not. You just want to make sure the device is safe in humans. And before you implant that device in a human, You… you did?

10,000 tests. 10,000 tests. You spend years and money. Doing the testing to… To put your reputation at risk as an investigator, because Again, the leaders of these companies are… or the leadership team of these companies I mean, top people, world-class people, the best brains in the world in medical device development, they are the people behind these companies. So they don't want to put their reputation at risk. And also, the reputation of the key opinion leader that they hired, like. I described at the beginning of the call, like, people like Dr. William O'Neill. etc. I mean, if you are a Harvard

physician, a cupino leader, or a John Hopkins physician, you're not going to get involved with a technology that is gonna harm people, that it's gonna… not gonna work. So you want to be part of something that… that is going to make you proud, right? So anyway, the point is that Safety is not really an issue. Most of the trials we get involved in is, I mean, patients We changed their lives. We literally changed their lives. They have a disease, they have a condition that has not been treated. For years, because of the reasons I said, the healthcare system doesn't want to treat them, it's too expensive, whatever.

And also because there is no treatment. I mean, again. These are innovations that get a lot of funding, From investors, because… investors from the United States, because it's a condition that has no treatment available in the United States. Right? This hasn't been any innovation. For example, back pain. There's no innovation. The past 30 years, 40 years, if you look at the history of back pain innovation, there's almost none. Very incremental. So the moment you come with… you come in the market, to investors with a very good product to treat back pain, investors are gonna jump on you, because it's an opportunity to create a unicorn!

in back pain, in the back pain space. Anyway, the point is that these companies are not really in the business of harming patients or anything like that. It's just that it does want to do something that is faster overseas, and patients overseas are just begging for these type of innovations, because they don't have access to these innovations.

That makes perfect sense.

Exactly.

I understand.

John, may I just jump in really quickly?

Yeah, we have to wind up, though.

I know, I know, but I think it's really important to mention that a lot of investors need to see the numbers in terms of the patients in order for them to invest.

Beautiful.

Based on my experience, it's insufficient. I mean, that was noted before. For me, it's insufficient for an investor to get involved. And they're really picky right now, and as I mentioned at the very beginning of our call, there is a noted downturn, and investors are really edgy, and so 5 is not going to do it.

Yeah.

Anyways, just to keep clear, thanks.

Yeah, that's a great point, Stephanie. I see… I see that 5 is not enough, but, it's increasing. Now, investors want to see more data, more and more data. Now, I think the magic number is 20. That's usually what my clients, Tell me about sweetie.

That's… that's helpful. Thank you both. So, we're right at 5 o'clock, in… Portugal. And I apologize again for, the late start and the confusion, and apologize to our speaker. Especially, I'd like to thank everyone for your patience. I hope that you'll join us again next week for, the QMS presentation. And I look forward to seeing you all soon. Don't forget to vote MLVX.ai slash MLV100. We've had over 3,000 votes submitted so far. and counting. So, voting is open until the end of the month.

please look for those posts, please share them, with your, with your colleagues, and nominate people. Again, thank you, Julio, and, and everyone who, who shared their time with us today. Until next week…

Ryan, thank you for having me here.

Thank you. Bye-bye. Hi, everyone.