Precision Care for Acne and Eczema with Oliver Liu of Hypothesis

Hey guys, welcome back to Skin Anarchy. This is a very special episode because we're gonna be covering a topic that I think we rarely get to sit down and speak about in detail and in full fullness in terms of the science. And so for decades, I know a lot of you have heard about acne, eczema, kind of the same way when it comes to the bacteria that are involved, the microbiome that's involved, but nobody dives into like what that actually means. I feel like we keep having this conversation and going in circles and not really getting to the nitty gritty of all of it. So our guest today is going to do exactly that and really talk to us in depth about the microbiome and really what that means for these different skin conditions. So without further ado, please welcome Dr. Oliver Lu who is the co-founder and CEO of Hypothesis. Welcome Dr. Lu, I'm so excited to host you. Yeah, thanks for having me. Really excited to have this conversation. Yeah, I'm really excited to dive in. I would actually love to start off with learning more about your background. I know you have such extensive experience in biochemistry, genetics, metagenomics. I mean, I'd love for you to dive into that and kind of walk us down on relaying and tell us about your background. Yeah, as you mentioned, the bulk of my career since my PhD has been in what's called metagenomics. Metagenomics is the study of communities of microorganisms, whether that be in the soil and a hot spring or on your body, like with the skin microbiome. The thing that makes metagenomics so interesting is that we honestly have barely scratched the surface of natural diversity. It's estimated that 99.9% of microbial diversity in the world has never been studied, primarily because we don't know how to grow them in the lab. That means almost everything we've learned, all these huge databases of species and genomic information, all these things come from just a small sliver of natural diversity. And the thing that I and my fellow co-founders at Hypothesis have learned, both at Hypothesis as well as at Radiant Genomics, the previous company I co-founded, is that if you do have a biological challenge, nature has almost always come up with a more elegant and effective solution than anything scientists can come up with in the lab. The answers are out there, often in those huge swaths of natural diversity that no one has looked at before. And metagenomics is a way for us to uncover those solutions. When it comes to the skin microbiome, we have been following that field for a while. So we know now that a well-balanced, diverse skin microbiome is critical for skin health. It helps to strengthen the skin barrier, train the immune system, prevent pathogens from colonizing. And over the past 15 years or so, the tools that researchers have to study and characterize the skin microbiome have improved tremendously. And so now we can not only look at someone's skin microbiome and see the specific species of microbes that make up the skin microbiome and their relative percentages in different parts of the body, we also have a much better understanding of what can go wrong in the skin microbiome, particularly when you have skin conditions like acne or eczema. And what we see in both those cases is that specific species of bacteria can overgrow in the skin microbiome and cause or worsen these conditions. In the case of eczema, that bacteria is called staph aureus. In the case of acne, this bacteria is called C-acnes. That's really interesting. And it really stood out to you, what you said about how we don't know about a lot, most of what's out there in the world of microbes. I mean, that's really fascinating. I think that really hits home for, I think, a lot of us, because we often think that now that science is diving into the gut skin access, the microbiome, like it feels like we haven't all figured out, but clearly there's so much to explore there. I would love for you to dive into, where did you see the biggest disconnect between what the science already knows, which I think you were talking about just now, about the microbiome and what's actually available to consumers? Yeah, so as I mentioned, so on the one hand, we increasingly have this very detailed mechanistic understanding of how specific bacteria can drive conditions like eczema or acne. These bacteria not just happen to be growing more, they are actually playing a central role in disease progression. On the other hand, the products that we have to treat these conditions haven't changed in decades, right? We're still using the same ingredients we always have, and they either don't really address the skin microbiome, things like colloidal oatmeal or stereocreams, or you have ingredients like benzoyl peroxide, antibiotics, disinfectants like hypochlorous acid, that are meant to kind of try to control some of this causal bacteria, but they're broad spectrum, right? And they indiscriminately kill all bacteria, including the good bacteria, your skin needs to stay healthy. So that's the gap that we saw when we founded Hypothesis. You have these skin conditions that are crying out for a precision approach, that's more than simply carpet bombing your skin microbiome. And importantly, we also thought we had the solution. We were inspired by a class of high specificity enzymes that are found in nature. And with these enzymes, we believed we could usher in what could truly be called precision skincare. And so over the course of two, three years of R&D, that's what we worked on. We developed these high precision enzymes that can specifically target either Staph aureus or C-acnees without damaging or affecting the broader beneficial microbiome. One of the things you see is, if some of these acne treatments aren't working for you, the suggestion often is to use higher and higher concentrations of these treatments and harsher and harsher things. And you're really starting to make a lot of trade-offs in terms of kind of collateral damage you're doing. Right, right, no, that's exactly it. You just keep upping it. And that's never the solution. But I wanna actually go back to what you were talking about. You were mentioning this new approach, this precision-based approach. Can you dive a little deeper into that? I mean, what enzymes? And just tell us more about that. Yeah, so when we started Hypothesis, we got really interested in a class of naturally occurring enzymes found in bacteria and in bacteriophages called Lysins. They're interesting for a couple of reasons. First is these enzymes are designed to bind to bacterial cell walls and chew them up very rapidly, causing the bacteria to burst and die. So kind of really rapid bacterial killing activity. It's like popping a balloon with a pin. The really interesting thing about Lysins though, is that because the structure of the cell wall can differ pretty significantly from species to species, depending on how an enzyme binds to that cell wall, it has the potential for very high specificity down to a single genus species or sometimes even a subspecies. And so that means potentially one of these enzymes could specifically target a single species of bacteria within a community of many different types of bacteria. And that potential for very high selectivity struck us as an incredibly powerful property. As we've talked about, most ingredients with these antibacterial properties like antibiotics and hypochlorous acid are broad spectrum. They kill all bacteria. And so the idea of being able to target a single species within the community seemed like, honestly like a superpower. And in particular, we thought the skin microbiome would be the perfect application. Yeah, that's, I mean, that's incredibly fascinating that you can really narrow it down to that level. I mean, I hope we can go in that direction with everything now that I'm thinking about it when it comes to skin health. Now I wanna dive a little bit deeper because we started the conversation talking about acne and eczema. And I think it's important for all of us to kind of revisit like eczema and really understand what's happening here. Can you break down the three driver model for eczema? So we can just kind of get our brains around this. Yeah, sure, absolutely. I think the best way to understand eczema is through what dermatologists call the itch-scratch inflammation cycle. So if you have eczema, that term sounds familiar and this process sounds familiar, right? It starts with, you know, you have a patch of irritated skin that might be a bit inflamed, it itches, you scratch it. And that scratching ends up causing more damage to the skin, which unfortunately triggers more inflammation, which triggers more itching and then more scratching. And you have that cycle that repeats getting worse each time. And once it gets going, it can be really hard to stop. And before that initial itch has turned into a full-blown flare-up. So we now know that three interconnected factors really drive that cycle and keep it going. The first factor is a weakened skin barrier. The outermost layer of your skin is supposed to act like a seal, right? It keeps moisture in and irritants, allergens, bacteria out. And people with eczema, this barrier is often compromised. Sometimes it's genetic. A lot of people with eczema have a mutation in a protein called phylagrin. That's important for building a strong barrier. But the barrier can also be damaged by, you know, things like physical irritation, inflammation, and even bacterial activity. So that's one factor. The second factor is an overactive immune system. Eczema-prone skin tends to overreact, tends to kind of overreact to things that generally should be considered safe. And so it's prone to inflammation that can damage the skin and drive itch. This inflammation also makes the skin more hospitable to harmful bacteria like staph aureus. And finally, the third factor, which is the piece that's really been uncovered over the past five, 10 years. It has been generally overlooked in eczema care previously, which is the microbiome imbalance, specifically an overgrowth of staph aureus. It produces toxins and factors that break down the skin barrier, increase inflammation, increase itching. And you can see how this directly feeds into the other two drivers. And so that's what's so challenging, right? These three drivers don't exist in isolation. They feed on each other to drive that itch-scratch inflammation cycle. And once that's established, it tends to start reinforcing itself. So what is this like with staph aureus specifically? Like you said, this is a really, like this is the critical one, the bacteria in eczema. Can you dive deeper into that? Like what about it exactly is making things worse? So this is a great example of how we have learned so much about the skin microbiome over the past 10 years. Dermatologists have long known that staph aureus is more likely to be found on individuals with eczema. So studies show that 70% to 95% of individuals with eczema are colonized with staph aureus, while only about 10% to 30% of the general population is. The question has always been, what does this mean? Is this correlation or is this causation? In 2012, there was this great paper that came out of the NIH that looked at how the levels of staph aureus change in people with eczema as they go through flare-ups. And what they found was that the level of staph aureus in the skin is not static. Instead, the amount of staph aureus actually spikes dramatically right before and during flare-ups. And the more staph aureus that you have, the worse your symptoms tend to be. And so this finding was really important. It kind of indicated that staph aureus isn't just this bystander on the inflamed skin, but it's actually an active participant. It's actually one of the big drivers and triggers that amplifies these flares. Since that study, other researchers have not only confirmed those results, they begin to uncover exactly how staph aureus drives that itch scratch cycle. It actually produces toxins, enzymes, molecules that break down the skin barrier, drive inflammation, crowd out other microbes. There was a paper that came out a couple years from Harvard Medical School that actually identified the specific enzyme that staph aureus produces that can activate a nerve cell that drives itch. And so this is the first time, actually, that they found a microbe that could directly trigger itching. And so it basically accelerates all the drivers of this itch scratch inflammation cycle. So it turns out staph aureus is really like, it's like the fuel on the fire, right? It's really what's revving up the itch scratch inflammation cycle. It turns that initial trigger into that full blown flare up. That's so fascinating. Like, I mean, especially with the nervous system integration that you just explained, that's really interesting. Now, in terms of like, now, I mean, staph, that's very interesting where I go about, but I know with acne, we hear about bacteria a lot more, especially with sea acne. It's like, can we dive into acne as well and talk about what we've been told about acne thus far, right? It's called bivacteria, but you say it's actually about balance. So can you kind of walk us through that? Like, what does that mean for acne? Yeah, no, absolutely. As you mentioned, in the case of acne, most people know that bacteria play a role, right? It's why, you know, you do see things like benzoyl peroxide or why dermatologists prescribe antibiotics. Why you see a lot of like antibacterial being a selling point. But just as with eczema, it's not all the skin bacteria that's involved in acne. It's driven by the balance of a specific bacteria called QD bacterium acne or sea acne. And actually, even in the past, you know, five years, our understanding has gotten even more nuanced than simply saying you have too much sea acne. In the past, it was thought that acne was caused simply by an overgrowth of sea acne, but now that we have much more detailed genetic studies of the skin microbiome, we know that people with clear skin often have just as much sea acne as those with acne. And sea acne is a normal permanent resident of your skin. It's actually one of the more abundant bacteria to face. We now know the problem is not necessarily how much sea acne is you having in the skin, but instead, you know, what subtypes or phylo types of sea acne dominate the population. In people with clear skin, these subtypes exist in kind of a relatively balanced distribution and they kind of keep each other in check. There's a lot of strains that are less inflammatory, but in acne prone skin, that balance shifts. And so there's one subtype in particular, known as 1A1, which becomes dominant. And so it could make up 95% of the sea acne's population on acne prone skin versus, you know, 30 to 40% in non acne skin. And this inflammatory subtype, you know, produces more light paces that break down sebum and into irritating fatty acids. And they generate more inflammatory metabolites. They're more likely to form biofilms. And so it's not necessarily, in the case of acne, it's not necessarily that sea acne's as a species is overgrowing. In general, it's more that there's a specific subtype of sea acne's that has taken over the population. That's really, I mean, that's really fascinating to learn about because, I mean, it really makes you then question this whole idea of what we were originally talking about where it's like the whole kill everything model. Like just nuke everything. Can you talk to us a little bit more about that now in terms of like why that doesn't really make sense then now that we know this? So as we mentioned, most molecules that kill bacteria, treatments like benzoperoxide, antibiotics, they indiscriminate kill bacteria, right? Including the good bacteria. So obviously you're losing out on the benefits of a diverse, well-balanced skin microbiome. All the good bacteria that your skin needs to stay healthy are being wiped out. I think it's also worth noting that wiping out large portions of your microbiome has other downstream effects. You're actually removing a lot of the healthy competitors that keep bad bacteria like staph aureus in check. So once you stop using these treatments, the bad bacteria can actually come back even stronger because their natural competitors are gone. And so, and then I think we talked about the harshness of like benzoperoxide. One other thing to note around antibiotics is that there's also a lot of issues with antibiotic resistance, right? So studies show anywhere from like 60 to 90% of siacne strains are resistant to some antibiotic. So that's both a public health problem and a practical problem for patients when their antibiotics aren't working. What is your opinion on why the industry hasn't been able to embrace this more precision-based model so far? Like why have we been stuck in this like nuke everything mode? Yeah, honestly, it's because, in my opinion, and I think it's because creating precision ingredients that actually can be highly selective for a single species of bacteria is actually a really hard biological challenge. You need an ingredient that somehow can tell the difference between different bacteria, right? Can kind of distinguish between one bacteria from another. Or you need to find some vulnerability that only your target bacteria has. And that's not easy to do, particularly with like simple chemicals, like benzoyl peroxide or hypochlorous acids, not even easy to do with more complex molecules like antibiotics. And so this is where we really took inspiration from nature because, of course, nature has solved this biological challenge in the form of these high-specificity enzymes. And you really do need the kind of the biological complexity of a large molecule like an enzyme that can actually distinguish between different bacteria. And so, you know, when we learn more and more about license, the more we thought, yeah, this would be the key to precision microbiome skincare. Yeah, I mean, it makes a lot of sense, honestly. And I like that you brought up the point about how there isn't a vast amount of resources required to create technologies like this. I mean, this is really worth noting is that it takes a lot of dedication in years and decades of science to come to this kind of understanding. So, I mean, that's huge. And I'm glad that you guys are doing it, honestly, because we need this approach. And now, how are technologies like TPZ-01 and CUT-02 different from traditional actives? Right. So, TPZ-01 and CUT-02 are two patented and proprietary precision enzymes. TPZ-01 is designed to specifically target staph aureus, while CUT-02 is designed to specifically target sea acnes. We spent two to three years developing these enzymes. I mentioned they're based on enzymes that are found in nature that we discovered in our research. We tested over 800 variants of these enzymes to find ones that kind of met the criteria and specificity that we wanted. So, in our laboratory testing, both of these enzymes kill 99.99% of their target bacteria, while having no measurable impact on a broad panel of beneficial skin bacteria. So, they have very strong and very selective activity. And because they only bind to their target bacteria and don't really interact with human cells, TPZ-01 and CUT-02 are incredibly gentle. They don't cause irritation or affect the skin barrier. We have done both tests on panels of sensitive people with sensitive skin or looked at 3D models of human skin tissue. In what we see, we confirm the enzyme has no effect on human skin cells at all, even at really high concentrations. And so, these have very few side effects. They're non-irritating. In our clinical testing back set up, 95% of participants that use our acne serum for eight weeks said it was non-irritating, they had no issues. Wow, that's amazing. And that's really amazing that they're so precise. Like, they're not interacting with the skin in any negative way. That's really, that's very fascinating. Now, I'm curious though, like, what is the biggest challenge? Because I always wonder, right, with like proprietary ingredients, like, it's got to be hard bringing that to like mass scale and putting in skincare. So, what were some of the biggest challenges that you faced bringing these enzymes over into skincare products? Yeah, it wasn't easy. So, we're not the first group to think about using license to manipulate the skin microbiome. Other labs, other groups, other companies have looked into it. I think historically, there have been three kind of big challenges in turning these enzymes into effective products. The first is that specificity. And there are a lot of license, you know, you can find license and while license have the potential for specificity, it can be really hard to find one that actually has a specificity you want, right? So, for example, there are a number of enzymes that have been found that target the genus, Staphylococcus broadly. But finding an enzyme that can distinguish between Staph aureus and its closely related species Staph epidermidis, which is actually a good bacteria, is really hard. And so, you know, finding that specificity and figuring out ways to distinguish between those can be quite challenging. In the case of acne, no one has previously been able to find an enzyme that effectively targets the acne. So, CUT02 is really the first enzyme that even really targets the acne in this class. So, specificity is the first challenge. I think the second challenge is that even if you can find an enzyme with the right specificity, you still need more from that enzyme, right? You need an enzyme that has high activity. It works, you want it to work at the right pH. You know, skin is ideally slightly acidic. And most importantly is highly stable. You're probably familiar. Enzymes are notoriously fragile. They're sensitive to heat. They can be damaged, they can be degraded. They just fall apart over time. And of course, when it comes to skincare products, shelf life is really important, right? So, you want a long shelf life at room temperature. So, that's both convenient for customers. Also, you need that long shelf life to let you sell through different channels like retail or Amazon. So, we had to work really hard to develop enzymes with very high stability and develop formulations that really protected these enzymes. So, we could achieve that two-year shelf life. Third challenge I think you alluded to is that you need to be able to produce these enzymes at large scale and cost effectively. We worked really hard to increase the production yields of our enzymes so that we can sell at accessible price points. Wow, no, that sounds incredibly like a true feat to be able to accomplish this. Yeah, I mean, it's really, I think that's one of my biggest, I'm always like in all of that when you look at innovation, the space and how it's brought to life. And skin care, like it's always very inspiring to see how much work goes into that because scaling is... Yeah, I was saying this is, and one of the reasons we also wanted to found hypothesis is that we did feel like we had, with our experience with metagenomics, with harnessing natural diversity, with our background in engineering biology, we felt like we had a new way and a new approach to try to overcome these historical hurdles. And so, as you could imagine, a lot of the ways we've been able to overcome these challenges by looking to find better enzyme candidates and better starting points, kind of by looking broadly in natural diversity where no one else has looked before. Yeah, I mean, I think that's very fascinating. I'm glad you're also highlighting that there is so much in nature that we can still use. I think that gets lost a lot of times, is that we can really go there and find solutions still. We just have to do the science. Like you gotta do the work. You gotta look into technologies that can bring that out. But I wanna dive deeper into your clinical results. I know you have immense amount of clinical data really backing up what you're doing. Can you dive into the clinical studies and what they revealed about how effective this approach actually is? Yeah, so I think this is where the kind of proof is really in the pudding, right? It's great to be able to show specificity and activity in the lab, but the question really is what happens when you apply it to the skin? So we have run a number of clinical trials. In the case of EGSMA, we ran what's called a dual arm formulation controlled clinical study. So we split our participants into two groups. One group used our EGSMA Precision Hydrogel, which contains our TPZ01 Precision Enzyme. They used it twice a day for two weeks. We then had a, we also had a second group, which is our control group, which used an identical formulation. Contain kind of same OTC levels of colloidal oatmeal, the same Provitamin B5. The only difference is that it did not contain the enzyme. Again, that control group used that control formula, formulation twice per day. We looked at EGSMA symptoms. We had them clinically scored by experts using the SCORAD rubric at baseline one week and two weeks. After two weeks, the control group saw a 25% decrease in EGSMA symptoms on average. The group that used the EGSMA Precision Hydrogel saw a 61% decrease in symptoms. So simply adding TPZ01 to the formulation improved results over two and a half times. Importantly, when we looked at the microbiome, the amount of staph aureus decreased by 85% in the group using our hydrogel, while there was no significant change in the control group. So we think this study was really a nice set of data that ties and demonstrates the performance of TPZ01 with its benefit. Yeah, that's really huge. That's really, really good. Yeah. Yeah. In the case of acne, we ran longer eight-week trials. So improving in acne is generally more gradual, and actually a lot of trials go out even longer, 16, 24 weeks. So we had participants use our acne precision serum, which contained CUT02 once per day, nightly for eight weeks. In these trials, we saw that 93% of participants saw improvement by week two, but with the most substantial improvements accruing over weeks four through eight. We saw significant improvements in all the symptoms that we tracked, including lesion count, redness, tenderness, skin tone. We didn't do a head-to-head with traditional treatments, but when we compare our clinical trial results to the clinical trials in the literature that are testing first-line treatments like combinations of antibiotic, spenzol, peroxide, and retinoids, the magnitude and pace of improvement that you see with the acne precision serum is comparable. So comparable, good efficacy, but with much less irritation, much better tolerance. Wow, that's really fascinating, because yeah, because the protocol for acne just feels so daunting. So that's really, really promising to hear that. Now, in terms of like, I'm gonna really put this in context for our listeners in terms of routines, because I think that's where a lot of us get stuck, right? Is like figuring out how to incorporate novel tech into our routine. So if somebody's using hypothesis products, what is a realistic routine that they can follow? Yeah, great question. I think this is really where science becomes kind of really practical for people, right? So for our eczema line, the routine is designed to be simple, consistent. We recommend starting with either our eczema precision hydrogel or our precision healing spray. Both contain TP-Z01 and same concentrations and are applied directly to the eczema prone skin. These are kind of the primary products for keeping staff aureus in check. You would apply them twice daily, morning and evening possible, and at least twice daily to the areas where you tend to flare. I think it's really kind of personal preference whether you use the hydrogel, the spray or both. Some people find the spray easier to apply to hard-to-reach areas or to use on the go. Some people find it easier to apply to children while other people like kind of a more traditional gel format. So we have kind of that piece that controls staff aureus. We also have an eczema therapy cream, which we recommend you follow on to any of the TP-Z01 products. And so this therapy cream contains clotomol, three essential ceramides. It's designed to moisturize and really strengthen or repair the skin barrier alongside the TP-Z01 products. So now that your skin has a chance to calm down, you can address both the staff aureus as well as kind of the skin barrier driver of eczema. If you do have active inflammation, I think that people should feel free to use a topical steroid as directed by a dermatologist if you're comfortable with it. Ideally, we think as you kind of get into the routine with the hypothesis products, you should be using any kind of steroids less and less over time as the microbiome stabilizes. Yeah, I would imagine it's a really good way to kind of wean off of those kind of medications also and not compromise your results and not compromise. Yeah, that's really, really interesting. I mean, I think this is where I get very fascinated also because this is where I think I said this before on the podcast where it's like we're really bridging at this point with dermatology in the skincare space. Like this is that kind of tech that's going to bridge that gap and it's going to give you an actual solution. That's not just going to be like another product in your routine. This can actually replace something that maybe you think is too harsh for your skin or that it's just not, maybe you've plateaued, plateaued with your results. And sometimes consumers don't know where to go after that. Even doctors don't know what to prescribe at that point. So, yeah. And in the case of Staph aureus, I think dermatologists are increasingly really appreciating the role of Staph aureus. There was some recent papers from a leading group of pediatric dermatologists that cited Staph aureus as the most critical driver of the H scratch inflammation cycle and contributing to eczema progression. And that is one of the highest kind of unmet needs in terms of eczema care management. So, I think there's really been this gap of how do you, even when you control kind of the skin barrier or you kind of control inflammation if you have all this Staph aureus on your skin, it either can keep the cycle going on its own or it's like priming the skin at the most simple provocation is just gonna kick that cycle back up again. And so, you're talking about the difference. Yeah, and Staph is very aggressive too. I mean, it's like wherever you see it in any pathology, it's an incredibly strong driver of pathology in all places of the body. Like, yeah, I mean, this is huge. I mean, in a lot of ways, because I mean, controlling something, a bacteria like Staph is very different than something that is not as aggressive. And I think that's important for consumers to understand is that that's probably why eczema treatments like have been failing for so long. It's like we have never addressed that root cause. So, this is huge, yeah. Yeah, and as opposed to siacneys, there's really no reason you want Staph aureus on your skin. And so, you want to get it removed if you can. And I think the other thing to, that as we get more and more data and information on other skin conditions, there's increasing evidence that Staph aureus is a contributor to all kinds of skin problems. Right, no, I want to talk about this because I really like products like this personally, especially dealing with adult acne, precision microdart blemish patch. Can you talk about what makes this different than any other patch on the market? Yeah, so for our acne line, we have three products. So, we have a daily acne cleanser, which is kind of a gentle, silk acid and glycolic acid cleanser that helps clear pores and prepares the skin for cut-o-two. We also have that acne precision serum, which is kind of the hero, right? It delivers cut-o-two directly to the skin. So, those two products act as a kind of daily routine that you're going to be using. What we've also developed, as you mentioned, are these precision microdart blemish patches. And so, this is actually a pretty hard technical feat, but we were able to figure out a way to formulate these micro needle patches with cut-o-two and have our enzyme kind of survive that formulation process. And so, these patches, as opposed to most pimple patches like hydrocolloid patches that kind of work passively, they sit on the surface of the skin and absorb fluid from a pimple to kind of accelerate this healing process, our precision microdart blemish patches are worked differently. So, they use these dissolvable micro needles to deliver cut-o-two into the pore where acne develops. And so, they're particularly effective at stopping the development of kind of early stage and under the surface pimples that haven't come to a head yet. It's those pimples that you can start to feel under your skin. You kind of know they're coming. There's a tender, but it hasn't really emerged yet. In our clinical testing, when people use our patch to kind of actively address those early stage pimples, 88% said the patch completely stopped the progression of the pimple, 97% said that it worked to flatten that under the surface pimple. So, whereas you use kind of hydrocolloid patches for whiteheads and pimples that have already kind of gone to the surface and you're really just trying to protect them and get them kind of healed, these precision microdart patches are really to kind of address and get at those early stage pimples and try to keep them from even developing in the first place. Also, this is actually, you're kind of debunking one of the misinformation out there too, because for a long time, I think people were using hydrocolloid patches as preventative when they're not. I mean, like that's, I've seen a lot of people do, I know I've done it, where it's like you just put them on because you think, oh, I'm gonna get a pimple right here, but then that's not doing anything for it to actually prevent it from developing. So, this is huge. I mean, it's a totally different way of thinking about it. That's very cool. I wanna actually ask you though, because I know that with microbiome-focused skincare, there's been a very big gap, I think, in the industry as far as the education around what we can realistically expect in terms of our routine and the efficacy and the timelines for resolution or whatever it might be. Can you kind of walk us through what users can realistically expect when they're starting a microbiome-focused routine? And how should we really be approaching this from a psychology standpoint? Yeah, that's a great question, because I think setting the right expectations is actually one of the most important things we can do for our customers, because acne and eczema are conditions where people are just eager for products that work for them, right? And so, I think the first thing to know is that results will build gradually, particularly with acne. This is an achievement that's gonna work overnight. The skins, the microbiome, the microbial ecosystem takes time to rebalance the acne, lesion, lifecycle. It means that pimples that are kind of already developing beneath the surface, before you start a new routine, will still appear in the early weeks. And so, when you look at our acne clinical trial, most people do start to see a meaningful improvement within one to two weeks, but really kind of the best results build over that kind of full eight weeks of consistent use. So the trajectory can be encouraging early, but really the full benefit takes time to develop. In the case of eczema, setting expectations can honestly be a little trickier, because there are definitely a percentage of our users that actually do see a fairly dramatic improvement within just a few days. And these individuals are probably in a point in their eczema flare cycle, where staff always is at its peak and really driving symptoms, and TPC-1 can bring that down fairly quickly. And of course, we celebrate those results, and it's incredibly fulfilling to know that our products provide such relief. But honestly, I think the mindset you really need around eczema care is that this is a, this is kind of really a long game. Eczema is generally a chronic condition that's going to ebb and flow. And your long-term goal really should be, how do you manage those three drivers of the edge scratch inflammation cycle that we talked about? If you can create a routine where you're pushing back against those drivers consistently, you can keep that flare cycle in check. You can reduce the occurrences of flare ups. You can reduce the severity of flare ups. Our products can have dramatic results in some cases, but it's not meant to be necessarily to be a magic bullet. It's another tool in your toolbox, in your dermatologist's toolbox to help you target a driver of eczema symptoms, Staph aureus that's previously been kind of completely unaddressed. And then the most important thing is consistency. When you're trying to kind of maintain kind of good microbe balance, like you need kind of sustained daily effort. It doesn't rebalance if from like occasional use, it's not, think of it less like taking a medication for, you know, when things are going poorly, but when symptoms flare and more like kind of building a habit that kind of supports your skin's long-term health. Absolutely. Yeah, I think that we should be doing that anyways. At this point, like as much money as we invest in our skincare, you guys, like we shouldn't be doing that because that's how things work. I mean, no, honestly, like I think that's also like, I think that's why also like I gravitate so much towards trying to understand the microbiome personally as a consumer myself because it's really like at the heart of like understanding how your skin functions. And that takes time. It takes persistence and like consistency in your routine. And I feel like this specific niche of skincare is addressing a serious problem consumers have had for so many decades where we're like, just bombard my skin, but I mean, and then I'm going to do nothing for the next week. And it's like, we can't do that. It's an organ. So, yeah. Absolutely. And I think what we're really excited about is we are finally kind of bringing the products and tools that allow you to do that type of precision skincare and gentle skincare that I think people have always wanted, but you know, it just hasn't been available. Absolutely. Now, do you think like, I just want to get your opinion on this, like in going into the future and seeing how skincare is evolving, do you think it will eventually come to a point of being as personalized as something like what we study in genomics or just precision medicine at large? I mean, do you think we're cutting there? Yeah. And I think that is kind of the long-term goal, right? Is this personalization at some time, at some point you want to be able to, you know, profile your skin microbiome, understand, you know, the specific distribution of different species and strains, and then be able to kind of select from the treatments that are tailored to your kind of specific imbalance. I think that's where we're going to get to, but I do think it's going to take quite a bit of work for it to be a real thing. I think one of the challenges is that they're, right now there's really no concept of an ideal skin microbiome, right? You know, people with healthy skin can have very different skin microbiomes. So there's a lot of ways that a microbiome can be right. Now we've made a lot of progress understanding how the skin microbiome can go wrong, and that's where we can make a big impact now. And I think in the near term, it's also going to be easier and more reproducible to remove a species from the microbiome than to consistently add species to establish microbiome, given the kind of dynamics and competition in the skin microbiome. But yes, you know, I think as we generate more and more data on the skin microbiome of both healthy individuals and those suffering from skin issues, our understanding of individual microbial profiles and how we can give them a nudge here and there to a healthier state is only going to improve. And I think with tools like our precision enzymes, with probiotic approaches where we're, you know, maybe able to introduce beneficial strains, I think we can get to a point where we can kind of provide routines and make recommendations with confidence. And, you know, of course, no conversation can end without a mention of AI. I do think AI could play a really important role here as we kind of really accumulate large kind of vast amounts of microbiome data. Yeah, absolutely. Now I'm really excited about this space, honestly, and watching it grow because this could technically replace the entire area of allopathic medicine. Like if you really think about it, like all of the drugs that are circulating in the acne space, like just right now, I'm not saying we need to get rid of them saying, it could really make you re-examine what needs to be prescribed. And I would love to see a world where we can get more precise with dermatology drugs because I've said this before on the podcast where it's like, we, like what you said was very fascinating, by the way, about the antibiotics, like how dermatologists are the largest prescribers of this. But at the same time, it's like, I feel like dermatology drugs that large are really dated. And that's genuinely my opinion. Like I feel like when I look at the rest of medicine and I see how quickly we adapt technologies, I don't know why we're not doing that in dermatology. And so it would be really cool to have a world one day where we can say, okay, listen, we can get way more precise and we don't need to compromise other organ systems in the process of treating things like acne. So yeah. And I do think one of the more near-term opportunities is going to be kind of expanding the breadth of these types of microbiome approaches where we started with acne and eczema because kind of our understanding of the microbiome is the most developed there. We kind of, we understand which specific bacteria driving those conditions. But there's a lot of research going on and skin microbiome is implicated in a growing number of conditions beyond just those two. I mean, you look at psoriasis, rosacea, seborrheic dermatitis, there was even a paper on the skin microbiome and wrinkles and aging. So I think as the science develops, we get a clear understanding of kind of the microbial signatures of these conditions. And the precision approaches become more relevant there as well. Absolutely. Now in closing, I would love for you to give us just, like impart some closing wisdom on us about like, what is one thing you would like people to know about acne and eczema? And like, if you were to give us like one thing, we should keep in mind. Always, yeah. Let's see. I mean, what I would say is that these conditions are not about eliminating bacteria broadly, right? They're about restoring balance in the skin's microbial ecosystem. Your skin has its own ecology. It has bacteria that has co-evolved over millions of years to protect us, regulate our immune system, keep harmful organisms in check. And when we treat those conditions by kind of carpet bombing that ecosystem, we're really working against the biology rather than with it. And so what excites me about where we are with hypothesis is that for the first time, we have tools precise enough to work with the skin's biology. We can reduce the specific bacteria driving harm without kind of dismantling everything around that. And I think that's fundamentally a new approach to skin care that's only possible with the enzyme technology that we've developed and one that can kind of really be called precision skin care. So I genuinely believe it's gonna change how people think about the experiences and how they think about an experience, and I'm excited for people to try it. Absolutely. Now, I really, really urge you guys, definitely check out the brand if you have not already. You can get all the information, the show notes of this episode. So scroll down if you're listening anywhere and make sure you go check out the website, check out the brand. I mean, I really urge you guys, let's really vote with our dollars when it comes to technologies like this because I think that we can shift, move the needle a lot. We can really move the needle as consumers. And I think if we make a statement in that way, like it really goes a long way for allopathic medicines. Like I can't say that enough times. Like I personally myself, I really believe that when you see real innovation, like get behind it because that will immediately impact how physicians and practitioners day to day are working with these diseases. And so I just, I'm just so excited about this, Dr. Liu, what you guys are doing. It's very, very exciting. And I really applaud your team for coming out with something so innovative. So thank you for sharing that with us. Yeah, thank you. Thank you for your kind words and thank you for having me.