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- [00:00]
A
Hey, guys. Welcome back to Skin Anarchy. This is a very special episode because we're going to 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 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 Liu, who is the co founder and CEO of Hypothesis. Welcome, Dr. Liu. I'm so excited to host you.
- [00:49]
B
Yeah, thanks for having me. Really excited to have this conversation.
- [00:52]
A
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 would love for you to dive into that and kind of walk us down memory lane and tell us about your background.
- [01:07]
B
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, in 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 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.
- [03:15]
A
That's really interesting and it really stood out to me 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, like the gut, skin access, the microbiome, it feels like we have it all figured out, but clearly there's so much to explore there. I would love for you to dive into, like, 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.
- [03:51]
B
Yeah. So as I mentioned, so on the one hand, we increasingly have this kind of 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. 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 steroid creams, or you have ingredients like benzoyl peroxide, antibiotics, disinfectants like hypochlorous acid, that are meant to 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, you know, carpet bombing your, 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 skin care. And so over the course of two, three years of R and D, that's what we worked on. We developed these high precision enzymes that can specifically target either staph aureus or acnes without damaging or affecting the broader beneficial microbiome. One of the things you see is, you know, if some of these acne treatments aren't working for you, you know, the suggestion often is to use, you know, higher and higher concentrations of these treatments and harsher and harsher things. And, you know, you're really starting to make a lot of trade offs in terms of kind of collateral damage you're doing.
- [05:37]
A
Right, right. No, that's exactly it. Just keep upping it and it just, that's never the solution. But I want to 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 like, just tell us more about that.
- [05:53]
B
Yeah, so when we started hypothesis, we got really interested in a class of naturally occurring enzymes found in bacteria and bacteriophages called lysens. They're interesting for couple 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 lysens, 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, hypochlorous acid, are broad spectrum. They kill all bact. And so the idea of being able to target a single species within the community seemed like, you know, honestly, like a superpower. And in particular, we thought the skin microbiome would be the perfect application.
- [07:13]
A
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 want to 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?
- [07:39]
B
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, you know that that term sounds familiar and this process sounds familiar, right? It starts with, you know, you have a patch of irritated skin, it 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. In 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 filaggrin. That's important for building a strong barrier. But the barrier can also be damaged by 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. Staph aureus 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, stretch, inflammation cycle. And once that's established, it tends to start reinforcing itself.
- [09:56]
A
So what is this like with staph? Or 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?
- [10:07]
B
Yeah. 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, you know, 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, you know, 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 on the skin is not static. Instead of 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 is actually an active participant, is 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 sapphires 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.
- [12:06]
A
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, staff, that's, that's very interesting. But I know with acne we hear about bacteria a lot more, especially with C. Acne. It's like, can we dive into acne as well and talk about what we've been told about acne thus far? Right. Is caused by bacteria, but you say it's actually about balance. So can you kind of walk us through that? Like, what does that mean for acne?
- [12:36]
B
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 antibiotics 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 imbalance of a specific bacteria called QD bacterium acnes or C. Acnes. And actually, even in the past five years, our understanding has gotten even more nuanced than simply saying you have too much C. Acnes. In the past it was thought that acne was caused simply by an overgrowth of C. Acnes. But now that we have much more detailed genetic studies of the skin microbiome and we know that people with clear skin often have just as much C. Acnes as those with acne. And C. Acnes 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 C. Acnes you have in your skin, but instead, you know what subtypes or phylotypes of C. Acnes dominate the population. In people with clear skin, these subtypes exist in kind of a relatively balanced distribution. They kind of keep each other in check. There's a lot of strands 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 can make up 95% of the C. Acnes population on acne prone skin versus, you know, 30 to 40% in non acne skin. And this inflammatory subtype produces more lipases that break down Sebum 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 C. Acnes as a species is overgrowing in general. It's more that there's a specific subtype of C. Acnes that has taken over the population.
- [14:37]
A
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. It's like the whole kill everything model, like just, 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.
- [14:55]
B
So as we mentioned, most molecules that kill bacteria treatments like benzoyl peroxide antibiotics, they indiscriminately kill all bacteria. Right. Including the good bacteria. Yeah. So obviously you're losing out on the benefits of a diverse, well balanced skin microbiome. All the good bacteria that your, that your skin needs to stay healthy are being wiped out. I think it's also worth noting that wiping out, you know, large portions of your microbiome has other downstream effects. You're actually removing a lot of the healthy competitors that keep bad bacteria like Staphoris in check. So once you stop using these treatments, the bad bacteria can actually come back even stronger because their, their natural competitors are, are, are gone. And so, and then I think we talked about, about the harshness of, yeah, like benzoyl peroxide. 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 C. Acne strains are resistant to some antibiotic. So, you know, that's both a public health problem and a practical problem for patients when their antibiotics aren't, aren't working.
- [16:02]
A
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?
- [16:13]
B
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, it 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, that's not easy to do, particularly with like simple chemicals like benzoyl peroxide or hypochlorous acid. It's not even easy to do with more complex molecules like, like antibiotics. And so this is where, you know, 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, 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.
- [17:22]
A
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 and years and decades of science to come to this kind of understanding. So, I mean, that's huge. And I'm glad that, I'm glad that you guys are doing it, honestly, because we need this approach. Now. How are technologies like TPZ01 and CUT02 different from traditional actives?
- [17:50]
B
Right, so TPZ1 and CUT02 are our two patented and proprietary precision enzymes. TPZ1 is designed to specifically target Staph aureus, while CUT O2 is designed to specifically target C. 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, TPZ01 and cut O2 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. And 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. And our clinical testing backs that up. 95 of participants, 95% of participants that use our acne serum for eight weeks said it was non irritating. They had no issues.
- [19:23]
A
Wow, that's, 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, 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 doing? We're some of the biggest challenges that you faced bringing these enzymes over into skincare products.
- [19:44]
B
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. There are a lot of licensed, you know, you can find lysens and while lysens 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 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 C. Acnes. So cut O2 is really the first enzyme that even really targets C. Acnes in this class. So specificity is the first challenge. I think the second challenge is that even if you, 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 that 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 lets you know 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've worked really hard to increase the. Increase the production yields of our enzymes so that we can sell at accessible price points.
- [22:09]
A
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 awe of that. When. When you look at innovation space and how it's brought to life in skincare, it's always very inspiring to see how much work goes into that, because scaling is. Yeah.
- [22:30]
B
This is 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 can 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.
- [23:02]
A
Yeah, no, I mean, I think that's very fascinating. I'm glad you. 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, you know, do the science like you got to do the. You got to do the work. You got to look into technologies that can bring that out. But I want to 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?
- [23:35]
B
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? Right. So we have run a number of clinical trials. In the case of eczema, we ran what's called a dual arm formulation controlled clinical study. So we split our participants into two groups. One group used our Eczema 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, you know, same pro vitamin B5. The only difference is that it did not contain the enzyme. Again, that control group used that control formulation twice per day. We looked at eczema 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 eczema symptoms. On average, the group that used the eczema 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 TPZ1 with its benefit.
- [25:16]
A
Yeah, that's really huge. That's really, really good.
- [25:21]
B
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.
- [25:33]
A
Yeah.
- [25:34]
B
So we had participants use our acne precision serum, which contained cut O2 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 kind of substantial improvements accruing over kind of weeks four through eight. We saw significant groups in all the symptoms that we tracked, including lesion count, redness, tenderness, skin tone. We didn't do head to head with traditional treatments, but when we compare our clinical trial results to clinical trials in the literature that are testing first line treatments like combinations of antibiotics, benzoyl 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.
- [26:26]
A
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 want to 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?
- [26:51]
B
Yeah, great question. I think this is, 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 TPZ01 in same concentrations and are applied directly to the eczema prone skin. These are kind of the primary products for keeping staph 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, 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 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, that piece that controls staph aureus. We also have an eczema therapy cream which we recommend you follow on to any of the TPZ1 products. And so this therapy cream contains colloidal oatmeal, three essential ceramides. It's designed to moisturize and really strengthen or repair the skin barrier alongside the TPZ01 products. So now that your chance has a, your skin has a chance to calm down, you can address, you know, both the Sapph aureus as well as kind of the skin barrier driver of eczema. If you do have active inflammation, I think 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.
- [28:36]
A
Yeah, and I would imagine it's a really good way to like kind of wean off of those kind of medications also and not compromise your results. Results and not compromise. Yeah, that's, that's really, really interesting. I mean, I think this is where I get very fascinated also because this is where I, I think I said this before on the podcast where it's like we're really bridging at this point with dermatology. If 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, it'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 plateau with your results. And sometimes consumers don' know where to go after that. Even doctors don't know what to prescribe at that point. So.
- [29:17]
B
Yeah, and in the case of staph aureus. I think dermatologists are increasingly really appreciating the, the role of staph aureus. There was a, some recent papers from, from a leading group of pediatric dermatologists that, that cited staph aureus as kind of the, the most critical driver of the itch scratch inflammation cycle and, and contributing to, to eczema progression. And that is, is one of the highest kind of unmet needs in terms of eczema care management. So I think there's, there's, 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, as 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, it's just going to kick that cycle back up again. And so, yeah, staph is very aggressive too.
- [30:11]
A
I mean, it's like wherever you see it in any pathology, it's an incredibly strong driver. Driver of pathology in all places of the body. Like. Yeah, I mean, this is, 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, this is huge.
- [30:40]
B
Yeah, yeah. And as opposed to C. Acnes, there's really no reason you want staph aureus on your skin. And so you definitely just, you want to get it removed if you can. And I think the other thing too, that, you know, as we get more and more data and information on other skin conditions, you know, there's, there's increasing evidence that staph aureus is a contributor to all kinds of skin problems.
- [31:02]
A
Right now I want to talk about this because I really like products like this personally, especially dealing with adult acne Precision, the Precision microdart blemish patch. Can you talk about what makes this different than any other patch on the market?
- [31:15]
B
Market, yeah. So for our acne line, we have three products. So we have a daily acne cleanser, which is kind of a gentle silic acid and glycolic acid cleanser that helps clear pores and prepares the skin for cut O2. We also have that acne precision serum, which is kind of the hero. Right. It delivers cut O2 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 microneedle patches with cut O2 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. Process. Our precision microdart plant patches are work differently. So they, they use these dissolvable micro needles to deliver cut O2 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.
- [32:36]
A
Oh, yeah.
- [32:37]
B
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. Whereas use hydrocolloid patches for whiteheads and pimples that have already gotten to the surface. And you're really just trying to protect them and get them of healed. These precision microdart patches are really to kind of address and get at those, those early stage pimples and try to keep them from even developing in, in the first place.
- [33:18]
A
Also, this is actually. You were kind of debunking one of the misinformations 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. I know I've done it where it's like you just put them on because you think, oh, I'm gonna get a, I'm gonna get a pimple right here. But then that's not doing anything for it to actually prevent it. So this is huge. I mean, it's a totally different way of thinking about it. That's very cool. I want to actually ask you though, because I know that with microbiome focused like 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, right. 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 focus focused routine? And how should we really be approaching this, like from a psychology standpoint?
- [34:12]
B
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 isn't a treatment that's going to work overnight. The skin's microbiome, the microbial ecosystem takes time to rebalanced. The acne lesion life cycle 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 meaningful improvement within one to two weeks, but really 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, it 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 staph aurease is at its peak and really driving symptoms and TPZ one can bring that down fairly quickly. And you know, of course we, we, 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 itch, 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 know, 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, it's not meant to be necessarily, to be a magic bullet, right? It's another tool in your toolbox, in your dermatologist's toolbox to help you target a driver of eczema symptoms, you know, staph aureus that's previously been kind of completely unaddressed. And the most important thing is like consistency, right? When you're trying to kind of maintain kind of good microbial balance, like you need kind of sustained daily effort. It doesn't rebalance 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.
- [37:02]
A
Health, absolutely. Yeah. I think that we should be doing that anyways at this point. Like as much money as we invest in our skin care, you guys, like, we should 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, you know, your routine. And I feel like this specific niche of skin care 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 gonna do nothing for the next week and it's like, we can't do that. It's an organ. So.
- [37:45]
B
Yeah, 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, you know, precision skin care and gentle skincare that I think people have always wanted, but, you know, that just hasn't been available.
- [38:01]
A
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 headed there?
- [38:18]
B
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 profile your skin microbiome, understand the specific distribution of different species and strains, and then be able to select from the treatments that are tailored to your 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 right now there's really no concept of an ideal skin microbiome. People with healthy skin can have. 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 established microbiome, given the kind of dynamics and competition in the skin microbiome. But yes, and 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 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 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.
- [40:12]
A
Yeah, absolutely. No, I'm really excited about this space, honestly, and watching it grow, because this could technically replace an entire area of allopathic medicine, if you really think about it. All of the drugs that are circulating in the acne space, like, just, just right now, I'm not saying we need to get rid of them, saying it could really make you re examine, like, 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. You're 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 at large are really dangerous. And that's genuinely my opinion. Like, I feel like when I look at the rest of medicine and I see how, like, quickly we adapt technologies, I don't know why we're not doing Latin 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.
- [41:15]
B
And I do think one of the more near term opportunities is going to be kind of expanding the breadth of these types of, of microbiome approaches. Where we started with acne and eczema, because our understanding of the microbiome is the most developed there. We understand which specific bacteria are driving those conditions. But there's a lot of research going on and the skin microbiome is implicated in a growing number of conditions beyond just those two. 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. Precision approaches become more relevant there as well.
- [42:01]
A
Absolutely. Now, in closing Lu, 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.
- [42:16]
B
Yeah, let's see. I mean, what I would say is that these conditions are not about eliminating bacteria broadly.
- [42:24]
A
Right.
- [42:24]
B
They're about restoring balance in the skin's microbial ecosystem. Your skin has its own ecology as 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 skincare. So I genuinely believe, believe it's going to change how people think about the experiences and how they think about and experience acne and eczema care. And I'm excited for people to try it.
- [43:25]
A
Absolutely. Now I really, really urge you guys, definitely check out the brand if you have not already. You can get all the information in 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, I mean, let's really vote with our dollars when it comes to technologies like this because I think that we can shift, we move the needle a lot. We can really needle as consumers. And I think if we make a statement in that way, like it really goes a long way for allopathic medicine. 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.
- [44:15]
B
Yeah, thank you. Thank you for your kind words and thank you for having me.