Masterclass Monday: Understanding the Fundamentals of Clinical Trials in Skincare ft. Timeline and Dr. Brad Currier

0:00Hey guys, welcome back to Skin Anarchy. This is the third episode in our Timeline Masterclass series. I hope you guys have been following along. We've covered so many amazing topics from things like mitochondrial health and understanding mitochondria to Timeline's approach towards longevity with their patented complex, which is MitoPure, which is actually urolithin A. So I hope you guys have been following along. But if you haven't, make sure you go back and catch up on those episodes because they're really, really amazing. So without further ado, I want to introduce you guys to our third guest in the series.

0:29He is the manager of clinical trials at Timeline, Dr. Brad Currier. Welcome, Dr. Currier. I'm so excited to interview you. Dr. Aksa, thanks so much for having me. Really excited to be here and having a conversation today. Yeah, no, I'm really excited to dive in. You have such an awesome background as well. I mean, you're really leading timeline in this clinical trial space. And I think there's so much we can learn from you when it comes to understanding, obviously, right, as consumers, what is the necessity of a clinical trial? What is the necessity of us understanding the clinical relevance of any brand?

1:03I think that's a huge area that I'd love to cover, but to get us started, I'd love to learn about your journey in this space as a scientist and what led you to Timeline, if you can kind of walk us down memory lane. Yeah, absolutely. So I've been at Timeline now just over a year, but flashing back a few years before that, I'm a Canadian, born and raised in the Toronto area, and I went down to do my bachelor's in St. Louis, Missouri. I was down there on a golf scholarship at the time and was really interested in sports performance. So I, while I was there, I got involved with an exercise physiology lab.

1:38And that really was just the light bulb moment for me of, I love research. It was really cool working with these elite athletes, trying to see what we can do to maximize their performance. And after I'd spent a few years there, I was getting a bit of an appetite for doing something that was a bit more applicable. It's fun to see if you can make someone a gold medalist instead of a silver medalist, but it was more exciting to me to think of doing something that could have a meaningful impact in hundreds of thousands of people's lives. And my grandparents were a big part of my upbringing and healthy aging really was an interest.

2:15So I went back to Canada to do my PhD in muscle physiology, where I was able to run clinical trials, really looking at exercise and nutrition in this aging setting where maybe people are exercising, maybe they're bedridden, but really looking at how we can see how these interventions impact our health and ultimately our ability to live a long and healthy life. So during that time, that was really where I developed some of the skills that ultimately brought me to Timeline, which was here managing clinical trials. And that's something that I know we'll get into, but Timeline is science first from the get-go.

2:57It's a huge team effort that we have here to make it possible. But that's a little bit of the arc of how I kind of went from, I guess, the Canadian trying to be an athlete to now having the absolute best time doing science to try to make a meaningful impact in people's lives. That's really cool. I love that you're a physiologist and you have this background in physiology because I often find myself having these conversations with people where I'm like, you know, we don't get enough training in physiology, in medicine or science. And I think that is one of the most critical components of understanding health.

3:30I think if you don't have that grasp on what is physiologically normal for the body, like that's where that's the baseline, right? So it's like, I think for a lot of consumers, we get so wrapped up in the pathology that we don't think about where is that baseline for us and where's the starting place. And so I would love for you to speak on this a little bit because you do, I mean, muscle physiology is very relevant to aging, obviously, as you know. And actually when we think even about the facial features that we're always trying to work on through aesthetic medicine, like what are your thoughts on muscle health and how it like kind of correlates with skin health overall?

4:08I certainly think there's a lot of parallels. I think one muscle in many cases is rightfully considered a key longevity organ. It's about 40 % of our body mass, so it's a huge part of us. And on top of just needing it for movement, it's very metabolically active. So a lot of our metabolic rate, actually about 80 % of it, is determined by how much muscle we have. So it is very important for our movement and metabolism. And I think there's a lot of parallels that we can look at with skin. One, skin is also very big. It is our largest organ, as we've probably heard many people say. But a key thing about them is that both muscle and skin are rich with mitochondria.

4:51And these are the organelles that are the powerhouse of the cell. Yes, they make energy. They do so much more in our cells too. But I think there's a really nice parallel between this massive organ in our body and the prevalence of mitochondria that we can draw a lot of parallels for aging and healthy aging. I love how you mentioned the skin features too, because that is something I think, at least so far in my experience, has been maybe underappreciated, which is just actually the muscles, say, in our face and how they atrophy or hypertrophy and how that impacts the facial image. So I think that's a fascinating area with not just how the actual skin is changing, but to your point about physiology, It's how all these things go together.

5:39Right. Yeah, exactly. And that's exactly why I wanted to bring that up to you because I hear so much, especially in the aesthetic space, right? Like the deeper you get into aesthetics, we're working with like neurotoxins and trying to relax muscles. And we are working on that plane. We're working very much on the muscle and the fascia and all of these components. But then when you think about longevity, we don't talk about it. We, especially in skin longevity, we talk about how is the skin laying on top of all these structures? And it's like, we got to get down to the root cause. We got to figure out like what's underneath and where does that, that health come in?

6:14And so I think that's where also where I get very fascinated with timeline because mitochondria are not tissue specific. They are everywhere. We have them in every cell in our body. So I'd love for you to talk to us a little bit about when you guys, when timeline was approaching just mitochondrial health at large, what are some of the big things in the clinical trials perspective that really stood out that you wanted to measure, that you wanted to get out there and say, we got to test this, got to show people the relevance of this like marker or whatever it might be? Yeah, absolutely. And so maybe even taking a step back, you know, Timeline's origin was looking at these foods that appeared to have prolific health benefits and the natural molecules in them.

6:58So I know you've covered it in the series already, but a key one was mitopure, urolithin A, which is a postbiotic that's formed when we digest polyphenols that are in things like pomegranates, nuts, berries. And the road to doing this research has not been short. It's over 15 years now that timeline has been researching mitopure, urolithin A. And through that time, we were really driven to say, okay, we're going to do things the right way. And when you find this interest in molecule that seems to be having some benefits, early on you're looking at preclinical models. So these are things like animal studies where you can measure lifespan, muscle health, much easier than doing a human clinical study.

7:39So it was known from an early stage that urolithin A was improving mitochondria. And as that progressed into clinical development or human trials, that was where you could start looking at the mitochondria but also other things in the tissue so i think the uh the knowledge that mitopure was having an impact on the mitochondria was known before even getting into clinical trials which originated with muscle in in timelands case and now of course with skin so the mitochondria target was known early on and has definitely continue to be a key pillar of how mitopure has its benefits. I think also one thing that's fascinating is that we don't, we're not really dealing with, I feel like in longevity, we're not so much dealing with like these before and after scenarios.

8:30I think it's more of like the long-term tracking. You're looking at long-term tracking. I mean, how does that really come into play when you're looking at it from a clinical trials perspective, especially for a brand, a consumer-facing brand, where do you think the relevance needs to be? And what are some things we should look for as consumers in these kind of studies that make them relevant to us and separate the fluff from things that might just be for marketing? A few things I've mentioned on that. One is just clinical trials, period. Clinical trials, the reason they are so important is one word, confidence.

9:07How sure can we be that something is having an effect. We're not looking for a skincare product or any other intervention without the hopes that it could do something beneficial for us. And clinical trials are the systematic way that we can generate the evidence to be confident in the effect something has. So certainly we look at how different products or ingredients can impact key aging features or other components of skin health. One thing I would highlight to consumers to look at in terms of the evidence that's available if you're considering a product one does it have clinical trial data has it been studied in humans and two if it has what did they show and you can often tell a lot based on claims that are around the product oftentimes in the cosmetics or skincare field i see claims that are around things like reported or self-perceived improvements and not objective benefits where say people might think they felt like their skin was more hydrated or they felt like their skin was more supple.

10:16But it's not necessarily saying that they've proven that in clinical studies. It's just an anecdote from one person. Whereas when you have data from clinical trial, you can actually calculate and look at, okay, how much did this product improve wrinkling? How much did it improve hydration? And so I think looking for those concrete claims, it's a bit of a unique situation from a regulatory perspective in the cosmetic space, but looking for those powerful claims that are substantiated by clinical data, I think that's one I've noticed in the consumer-facing messaging that I see a difference between the brands doing it best and the ones that are some of the fluff that you talk about.

10:57Right. No, that's really fascinating because I think also with topical, and I want to kind of dive into this part, especially because with topical products, this becomes even more hazy, I think, for consumers. Because I mean, I know I have a hard time sometimes believing, trusting that there is relevance here in the clinical data that I'm looking at. What are some of the hurdles with topical products when it comes to really doing a robust clinical study? yeah with the topical products specifically i think the the biggest one at large just from the field is that there's not as much standardization as there would be in say the pharmaceutical industry where there's a pretty clear progression of if you want to get something approved and be able to sell it or take it it's got to go through some certain checkpoints the the rigor is less in nutrition and cosmetics.

11:51So it does put the onus on consumers and practitioners to kind of separate the wheat from the chaff, to see the signal in the noise. I think some of the practical hurdles that people will encounter if they're trying to do this are things like cost, time, and expertise. These studies, it's not a cookie-cutter method. Depending on what type of product you're testing, what type of outcome you're looking at, there's a specific method that would be best or the gold standard way to determine if that product has an effect. So I think that's one where we need to do an increasingly good job as people in the space of educating consumers on how that may look.

12:37So I think the hurdles to doing clinical trials are things that a lot of brands will cut corners on. If they don't see the benefit or they don't think it's worth a while, then they won't take the time and the money to actually invest in doing the clinical trials and generating the evidence so you know that you're delivering the best possible solution. Yeah, I like what you said. It's like this whole idea of cutting corners because that has been, for me, when I look for any data, I'm always wondering. It's always in the back of my mind. It's like, well, what didn't you look at? What did you really base this around?

13:13I feel like there's a way to bias some of this stuff. I feel like when you really have a company that does it right, it becomes obvious. And when you don't, it's really hazy. because there's a lot of brands. They're like, there's one clinical study that they've done. And I'm like, that's not enough. Like, I need to see more. I need to see what were all your endpoints. How many angles did you look at this with? So I think that's where I get very lost as both a consumer as well as a scientist because I'm like, I don't know if I can believe you flat out. I don't feel like I can. And that's why I asked you about topicals because topical, there is no standardized model for the skin.

13:51We have these things now with organoids, Human and organized systems are coming out more and like people are utilizing them more and more for these kind of reasons. But even that is just too early sometimes, I feel like, when it comes to things. You're absolutely right. And maybe I'll give an example because I realize maybe some people have varying experience with clinical trials. I know you and I live in this world. So we know, but one example that maybe consumers can look for if you're thinking about a product, one that you'll just see in the marketing, if they say they have human clinical trials, a second one would just be if that's published.

14:27Most brands that have done the research, well, brands that have done the research, that's a huge differentiator because like you said, there's so much noise. So that publication should be readily available on, say, their website. It shouldn't be hard to find. Right. An example of what you might look for to the bias point, because you're right, there's no standardized procedure. And maybe just to illustrate that, say, if you're developing a new drug and you want to take it through clinical testing, a key part of that process is pre-registering your trials. So this is a process where scientists who are about to run a study will publicly declare what they're going to do, what people are they're going to do a study in, what they're going to measure, how long the intervention will be.

15:10And this is a this is a national public registry that you can look at. And then when they report the results, you can go back and look at if they actually did what they said they were going to do before they started. This is something that there's no standardization in the cosmetic space. And if one example of when you see companies or organizations that do high quality research, even though it's not required, they go that extra mile and say pre-register trial, publish the study. So there's a few things like that, maybe just to differentiate on where some fields are standardized and this one is not.

15:48Yeah, that's a really, those are really good points, actually. Thank you for mentioning that. Yeah, that's, I mean, I couldn't agree with you more. That makes a lot of sense. And sometimes these are not published. You're right. Like a lot of times brands will just say it on their website. They'll just literally list it like under extra information or something like that. But then you can't find the paper. And a white paper is not a publication. Right, exactly. Yes. Yeah, thank you for saying that. And this is so important for all of you listening out there. I really think we are getting into that realm now with skincare, especially where we're allowed as consumers now start demanding.

16:22this. We have enough companies doing it right to where we can say, if you're not doing it, that means you're not doing it. Don't sugarcoat it to us. Just say you didn't do it instead of masking it or pretending. So yeah, I mean, I just want to say that. I completely agree. It's disingenuous if you're not, right? Where the mission, I think with the people who, the companies who are in it for the right reason and the people and consumers, what they're looking for, same mission. We're trying to improve our skin health, our skin longevity. And if we're truly committed to that mission, then things are going to be done the right way.

16:57And you'll see that from the companies that are doing that. Yes, I agree. Now, I want to actually dive into timelines data because it's wonderful and it's very, very clear to me why the brand works so well. I know I have seen huge changes in my skin since I've started utilizing it. So I guess I'm Like for myself, I'm living proof. My skin definitely has improved since I used the products. And I would love to learn about what were some of the major endpoints you were looking at with some of the products? I mean, I know one of my favorite products was the serum. I really love that product. If you could kind of dive into that for us.

17:32Yeah, absolutely. So the line has expanded just over the last year with the addition of the cleanser and exfoliator. For that, there have been four key products. The serum, obviously, that's a great, great product. really enjoyable experience. And I'm newer to skincare in the last few years as a user, admittedly, for improvement. And my better half makes sure I stay on it. So that's a new one, but the serum is a brilliant feeling. And the other three are creams. So one, an eye cream, a dewy cream, and a barrier cream. Now, we just finished up the 12th clinical trial that we've on timeline products.

18:15And those first few trials, after showing the safety of these products, some of the key endpoints I would consider canonical or hallmark skin aging targets. So these will be things like skin wrinkling, skin hydration, skin barrier function. And really they kind of are representative in many ways of how the skin is aging. So wrinkles we can all think of is how much are the wrinkles changing but also how is the structure changing like are they are they deeper are they shallower after using a product and that's one that we do see uh with the products improving now we can we can pick any trial because they've all uh they've all included it and they all it's all showing a beneficial effect but usually you'll see anywhere in the range of depending on the duration of the study you know 10 to 30 reduction in wrinkling over a month or two to generalize 10 trials into one.

19:14That's kind of the range people typically, or that we typically observe in the clinical studies. And the eye cream is a really neat one where it actually just came out last year too, but fascinating data and really showing some of the best efficacy data in terms of how well it does reduce those wrinkles. So I think they're all great products and we've started to apply them into different scenarios, But skin wrinkling, hydration, barrier function, those are all things that we're looking at to get a complete picture of how these products are benefiting our skin longevity. Yeah, that's interesting.

19:52That's huge, though. That wrinkle reduction number, that's really huge. It's better than most that I've ever come across because people never say that. They always say, like, oh, well, fine lines were reduced and pores were blurred. No one ever just outright, I think, says these days we actually saw a reduction in wrinkles and the depth and all that. So that's very, very fascinating. I can definitely see that. I mean, it's a great product. But I want to actually dive into a little bit more because one thing that I think a lot of people are trying to understand right now, especially in longevity, is there are these like very much pillar molecules, just the ingredients that we are looking at, right?

20:32in the skincare longevity space. For Timeline, that's Eurolethine. It's MitoPure, and the brand also markets itself as being mitobiotic. So what does that mean from the clinical trial lens and the data lens? Yeah, so I think mitobiotic, it's a great and well-fitting name. So biotic simply just means a living organism, right? And mito, obviously, mitochondria. I think the mitobiotic phrase and name really captures nicely that we are living organisms that need to be nourished and so are mitochondria and that's exactly what we're trying to do with these formulations is support our entire the entire ecosystem that is our body and the not just the some cells but all the components of our cells so from a from a clinical trial perspective that goes back to the the original studies where it was looking at, okay, what is the mechanism of action of things like urolithin A?

21:33Now, we know from the previous studies going back now, I guess, 10 years or so, it's benefits on mitochondria health. But when we wanted to look specifically at the skin, it was saying, okay, what's it doing that's unique to the skin? And in one of the first studies, it was a bit more invasive where we took skin biopsies from people using what's now the barrier cream. And after using the product, we did a deep profiling of what genes and proteins were changing following use. And you did see this significant upregulation of collagen synthesis and organization. So showing that by using this product, that there was a benefit unique to skin in that the collagen matrix and what's comprising the skin was improving with use.

22:18So from a clinical perspective, that early finding of how is this molecule actually working informed some of the things we might target or try to improve in future iterations. It's really interesting because I think one of the biggest questions I think I have, and I'm glad that Timeline, I just want to say this before I ask another question, one of the things I'm glad about Timeline is that you guys aren't just using buzzwords. People have so many proprietary names these days, and I think that's really important for consumers. So for everyone listening in, longevity to me, especially in skincare right now is interesting because of that, because you can't make claims as a company about fluff anymore.

23:02I feel like, I think there's like two camps that we're in where people either believe that it's like this big over umbrella term, but then I'm more so in the camp of like, no, I think it's more precision than anything else. So like, that's why I asked you about like, what is actual, What's the meaning of mitobiotic? Because that is an actual term that's being utilized to describe biology. And so when we're looking at longevity skincare, it's important to kind of make that differentiation rather than just saying like, oh, this like blurs your skin or whatever. I think for consumers, this is the era of precision more than anything else.

23:35I think with our conversation and what we're talking about from the data side, it's very relevant to kind of have that overarching theme, have that in our mind when we're looking at these kind of products. Okay, this should be precision-based. It shouldn't be just random marketing terminology and whatnot. Yeah, absolutely. I completely agree. And it does capture it nicely where it is the mitochondria is important and we're just nourishing it because we're a living organism. That's all we're trying to do is keep everything healthy. One of my biggest questions, honestly, from the clinical data side is what is the biggest hurdle with measuring something like an organelle?

24:15Mitochondria are so small and there's so many of them. And we know, in my opinion from science, we know so little about them. We're still learning so much. What, in your opinion, is the hardest part about studying something like that? Well, I think the hardest part, and I wouldn't say even that maybe it's the difficulty because we're very fortunate, especially at Timeline, we've got some world-class scientists, the best in the world at what they do in their fields, and they at least make it look easy. I don't know how they do some of the microbiology and formulation. It wows me every day what the team does.

24:52But I think something that's so important when doing clinical studies is that you're intentional with the design of the trial or what you're doing. Because you want it to be worthwhile. You want it to be novel. But you don't want it to be redundant or superfluous. So I'll give you an example in that. I talked about how in the early skin, one of the first few skin trials that Timeline had done, collected those muscle biopsies and got an idea for the cellular mechanism of how this product or this active was having an impact on skin. in subsequent trials we don't always take biopsies because we've we've generated that data we understand what's going on and skin biopsies are a burden on the participant now when you have a skin biopsy it's relatively easy to look at the mitochondria you separate all the cells you break them down and you can isolate those organelles and parts of a cell but that's not always necessary when you've established how something works at the cellular level ultimately we want to target that cellular health to cascade and impact the overall physiology.

26:07So now with a lot of the trials we've run, it is more what we call a phenotypic or a physical outcome where the mechanism is understood. And now we're seeing if different outcomes such as barrier function or skin wrinkles or hydration are impacted differently because that's a lower burden on the participant. So I think it's really important when human research to make sure that at the end of the day, you've got human volunteers willingly participating in these trials. And you want to make sure that whatever you're measuring, it is worth their while. And so that what I would say is how we've kind of transitioned from the cellular based work in clinical trials to now the efficacy type trials, looking at how well something ultimately accomplishes our goal.

26:56I love that. I love that you guys have jumped into actual human trials and you're looking at real skin. That's huge. That's absolutely huge. And I, honest to God, I have had this like, I've been on this rant, I feel like for years at this point, where I'm just like, please get out of the Petri dish. Let's go to human skin. We got to look at the skin. We got to look at real patients. We have to, unfortunately, there are so many ingredients that really pop up on the market these days, where it's like the only study they'll have is that one in vitro study. and people will you know what i mean and it's like immediately like the marketing kicks in immediately everyone's like yeah this is gonna fix everything and my fat pads are gonna recover all it's just insane and so i think that's amazing that you guys are just so focused on no we got to look at this in real human skin that's understand the science but also know the product right and i think that's something really unique about timeline is that every product that We market has been studied in clinical trials with humans.

27:55And it actually, you just saying that made me think to your earlier point about differentiating claims that are maybe a little bit of fluff versus legitimate claims. And you'll see that a lot when a company hasn't done clinical trials is how the, is the claim on the product or is it on the ingredient? Now, don't get me wrong. Ingredient claims are super important to know that a certain part of that formulation has an effect. But if there's no statement saying that the product has been shown to be safe or have these effects, then oftentimes you'll just get people mixing a few ingredients together and claiming based on what they put in it and not on what the complete product does.