Thank for standing by, and welcome to Jeune Aesthetics Interim Clinical Data Update Call. At this time, all participants are on a listen-only mode. After the speakers' presentations, there will be a question-and-answer session. During the question-and-answer session, there will be a limit of two questions per participant. As a reminder, today's conference is being recorded. I would now like to hand the conference over to your host, Stéphane Paquette, Vice President of Corporate Development at Krystal Biotech. Please begin. Good afternoon, and thank you all for joining today's call. Earlier today, we announced positive interim safety and efficacy results for Jeune Aesthetics' KB301 program in the treatment of lateral canthal lines at rest and dynamic wrinkles of the décolleté. The press release is available on our website at www.krystalbio.com. Both the press release and today's presentation have also been filed as an 8-K with the SEC. Joining me today will be Krish Krishnan, Chairman and Chief Executive Officer of Krystal Biotech, Dr. Steve Yoelin, one of the principal investigators on the PEARL-1 study, and September Riharb, Senior Vice President of Jeune Aesthetics. This presentation will, and our responses to questions may, contain forward-looking statements. You are cautioned not to rely on these forward-looking statements, which are based on current expectations using the information available as of the date of this webcast and are subject to certain risks and uncertainties that may cause the company's actual results to differ materially from those projected. A description of these risks, uncertainties, and other factors can be found in Krystal Biotech's SEC filings. With that, I will turn the call over to Krish. Thanks, Stéphane. Today, we're excited to be sharing the KB301 clinical update that highlights the potential of our unique and fundamentally rejuvenative approach to aesthetics. Before sharing the data, I'd like to talk about how Jeune is structured and the support that Krystal currently provides to Jeune. Jeune is a wholly owned subsidiary of Krystal and leverages Krystal's proprietary technology platform in aesthetic medicine. It's a validated platform that to date has produced one approved drug, Vyjuvek, for the treatment of dystrophic epidermolysis bullosa. That approval demonstrates, A, that we can safely and effectively deliver genetic cargo to the skin, B, that we now have commercial-scale manufacturing infrastructure approved by the FDA and EMA and by the PMDA in the near future, and C, a familiar platform to the FDA that enables faster development timelines and thereby significantly de-risking our aesthetics programs at Jeune. Presently, Jeune Aesthetics is basically a clinical development company, with Krystal providing support on the research pipeline, manufacturing, and regulatory interactions. Jeune's approach to developing treatments for aesthetic conditions is conceptually similar to our disease platform, and in Jeune's case, the objective is to reverse the declining trend of collagen and the extracellular matrix associated with aging. Here is a one-minute animation that describes our approach. The appearance of youthful, healthy skin relies on key proteins such as collagen and elastin. As we age, production and maintenance of these proteins declines, resulting in thinning of the skin and wrinkle formation. Jeune is developing groundbreaking technology to naturally rejuvenate the skin, consisting of a specially engineered vector that can carry genes for multiple skin proteins. Following injection, the genes are delivered directly into skin cells, boosting the ability of the cells to produce the encoded proteins. The body's natural systems are therefore leveraged to replenish the key structural components of skin that are normally lost with aging. By being designed to restore and rebuild, Jeune's technology has the potential to improve skin quality and appearance. As you saw from the video, our vector platform provides significant flexibility with the capacity to deliver one or multiple genes to the skin. Jeune's lead product candidate is KB301, which delivers the COL3A1 gene that encodes the pro-alpha-1 chains of type 3 collagen. We selected COL3 as our first candidate because it's critical for maintaining youthful and healthy skin. Humans have abundant amounts of Collagen Type 3 when young, and as we age, production of Collagen Type 3 diminishes, which is one of the primary contributors to thin-aged skin. KB301 is designed to supplement COL3 expression from an individual's own skin cells, restoring collagen levels and rejuvenating the skin. When we began the aesthetics program, our objective was to narrow down to one indication, to advance into Phase II and pivotal studies that had a decent chance of approval and one that addresses a fundamental unmet aesthetic need in this huge market. And here is how we narrowed down to an indication of choice. Having established safety in cohort I, we evaluated KB301 in a few different areas to establish initial proof of efficacy in our cohort II efficacy study and to ascertain the durability of expression. The learnings from cohorts I and cohort II were used to narrow down and conduct a proof-of-concept open label study in two indications: lateral canthal lines at rest, also referred to as smile lines or crow's feet, and dynamic wrinkles of the décolleté. Today, you will hear about results from these two indications and the indication we have chosen to move forward with. As we shared prior, our initial efficacy study was a multicenter, randomized, split-body study. We looked at efficacy in the skin above the upper knee and above and below the facial cheekbone. We had clinically meaningful efficacy and evidence of pharmacodynamic effect across all three injection sites. Above the knee, we saw a roughly 1.7 mm increase in skin thickness, as measured using a caliper, consistent with COL3 expression and our skin rebuilding mechanism, and in the upper and lower cheek, we saw clear improvements in subject satisfaction. Additionally, injection site reactions were all in line with what is seen in aesthetic injections, and they were mild to moderate, transient, and declined in frequency with repeat dosing. We followed the subjects who had been randomized to high-dose KB301 in the lower cheek up to nine months following the treatment in the cohort II durability study. The results showed sustained efficacy up to nine months after treatment. This finding shows that the natural skin rejuvenation with KB301 is stable and sustained for an extended period of time. Based on this initial data and following discussions with scientific advisors, we narrowed cohort III and cohort IV down to two indications that you see on this slide. Lateral canthal area of the upper cheek region is a fast-responding area to treatment. These smile lines, especially the lines that are present when not smiling, are one of the earliest appearing and most concerning areas of aging for consumers, and the FDA has not approved any aesthetic injectables for this indication. Like the lateral canthal skin, the skin of the décolleté is very thin and delicate, making it very difficult to treat with current available options. The décolleté is also one of the first areas to show signs of aging and is a highly concerning area for many people. Again, the FDA has not approved any aesthetic injectables for this indication. I'm now pleased to turn the presentation to Dr. Steve Yoelin, one of our investigators in the study, who will introduce the studies and share the interim results. Thank you, Krish. PEARL-1, cohort III, is an open-label study of KB301 in the lateral canthal lines at rest, which are the lines next to your eyes, known as smile lines or crow's feet. The lines at rest are those that are still present even when you are not smiling. We evaluated KB301 safety as well as efficacy in this study, with efficacy assessed by both the investigator and the subject, utilizing the Global Aesthetic Improvement Scale, or GAIS. Subjects also reported on their overall satisfaction with their wrinkle appearance using the Subject Satisfaction Questionnaire. We evaluated KB301 dose and injection technique in this cohort, with six of the subjects being injected by microneedling and seven by standard syringe. In today's interim readout, we will be presenting safety and efficacy results for the combined study population, as assessed one and two months after completing three weekly treatments. Safety findings are summarized here. KB301, at both low and high doses, was generally well-tolerated, with a safety profile consistent with previous clinical studies. Injection site reactions have all been within the expected range of aesthetic injectables, with all reported as mild to moderate and transient, and we have not seen any increase in the frequency or severity of adverse events with repeat treatment. We saw clear and clinically meaningful improvements in lateral canthal lines in KB301-treated subjects. Starting with the GAIS results, investigators reported an improvement of one point or better in over 90% of subjects at the one-month time point, and 50% had a two-point improvement. At two months, 75% of subjects were assessed as having a one-point or better improvement, and again, 50% with a two-point gain. Subjects also self-assessed meaningful improvement, with at least 50% reporting one point or better improvement at both one and two months. Consistent with our GAIS results, 2/3 of subjects reported increased satisfaction with their wrinkle appearance at the two-month follow-up. We were encouraged by these positive findings and the promise of having a primary treatment for this challenging area that is extremely concerning to my patients. In addition to wrinkles, the GAIS tool also captures other key skin quality attributes. As this slide shows, KB301 is having a clinically significant impact on crepey skin, the elastic quality of the skin, overall skin hydration, radiance or reflectivity of the skin, and the skin's texture. This is an exciting finding and points to the potential benefits of KB301's unique mechanism of collagen-free replenishment to meet the strong demand among injectable aesthetic users for products that go beyond wrinkles and address the overall quality of the skin. Here is a before and after picture of one of the Cohort III subjects. Her lateral canthal lines, or LCL, at rest at baseline was mild, and by month two, the lines had softened significantly with the rebuilding and rejuvenation of the treated skin. This subject is an older patient with deeper lines and a higher Fitzpatrick skin type. KB301 treatments showed the same level of clinically significant improvement in this subject, with the rebuilding of the skin and the softening of the LCLs at rest, or lateral canthal lines at rest. Overall, KB301 exhibited promising efficacy in lateral canthal lines at rest across patient types with a safety profile in line with injectables commonly used today. As Krish mentioned, the décolleté, the triangular area of the chest that includes the cleavage, is another aesthetic target site with no approved injectables and a frequent priority area for aesthetic patients. Cohort IV follows a similar design to Cohort III to evaluate KB301's safety, as well as efficacy in the treatment of dynamic wrinkles of the décolleté. Again, efficacy and satisfaction were assessed using the Global Aesthetic Improvement Scale and Subject Satisfaction Questionnaire, with follow-up at one and two months following treatment. A total of eighteen subjects were treated and assessed through the two-month follow-up. All subjects in this cohort are women. Only high-dose KB301 was utilized in this cohort, and the injection technique was with a standard syringe only. Subjects received three weekly treatments and were assessed monthly for the next two consecutive months for this interim data report. Injection site reactions were again within the expected range of aesthetic injectables, with all reported as mild to moderate, and all events were transient and resolved, and as with Cohort III, we haven't seen any increase in severity or frequency of adverse events with repeat treatment. In comparison with lateral canthal lines, we saw superior improvements in wrinkles of the décolleté following KB301 treatment, as well as a trend of greater improvement with time. Investigators reported an improvement of one point or better in over 80% of subjects at the one-month time point, and 28% had a two-point improvement. At two months, 94% of subjects were assessed as having a one-point or better improvement, and again, 28% had a two-point gain. Subjects also self-assessed meaningful improvement, with over 60% reporting one point or better improvement at one month, increasing to 89% at two months. The proportion of subjects reporting a two-point improvement also increased to 39% at two months, and consistent with this trend, 94% of subjects reported increased satisfaction with their wrinkle appearance at the two-month follow-up. As with Cohort III, in addition to wrinkles, other key skin quality attributes were assessed by GAIS, and in line with the strong improvements we saw in wrinkles, we also saw meaningful improvement across the queried skin attributes, with investigators reporting a one point or better improvement for all five attributes in over 85% of subjects at two months. Here is a representative picture of a cohort IV subject, and you can see how the extended wrinkles visible at baseline completely disappeared by month two. This is an older subject with extensive wrinkling and crepey skin at baseline, and you can see how the skin has rebuilt in this older subject by month two. The crepey skin has completely disappeared in the middle of the chest. Finally, this is an example of a very light Fitzpatrick skin with deep-set cutaneous wrinkles at baseline. By month two, her décolleté had no wrinkles, and her pigmentation was significantly improved, and now I'd like to hand off to September Riharb to discuss Jeune's plans for KB301 moving forward. Thank you, Dr. Yoelin. With evidence of improvement across multiple skin attributes and high levels of subject satisfaction, we believe that today's results highlight the potential of our fundamentally rejuvenative approach to restoring youthful vibrancy to the skin, and progressing towards the goal that Krish laid out at the beginning of today's call, today's results also provided us with the necessary information to nominate the décolleté as our target indication for phase II development. This is a decision based on both the lack of available therapies for the indication, as well as the profound improvements we saw in the cohort IV subjects. Moving forward, the next step is for us to engage with the FDA on study design and scale development. Once we have developed a KB301 specific scale and assessment tool for patient-reported outcomes, we will then proceed to phase II, which we expect to start next year. We are excited to have progressed KB301 through this key development milestone and will soon undertake the next phase of clinical study. Based on the unique mechanism of KB301, we believe this product and our Jeune pipeline are well positioned to disrupt and revitalize the aesthetic treatment paradigm. Let's look at today's market and the skin rejuvenation opportunity. Today's primary aesthetic tools are not designed to rejuvenate the skin. Fillers are designed to replace fat and bone loss as a result of the aging process, and neurotoxins paralyze muscles that create dynamic wrinkles. The third leg of the stool, as we call it, i.e., skin rejuvenation, is a category that is at least as large as the other "legs of the stool," but it has no primary tool today. The ideal primary skin rejuvenation tool will address the root cause of the issue, i.e., replenishing the skin's key proteins to rebuild the skin naturally, be injected with standard syringes, and be shipped and stored as other aesthetic injectables, and lastly, not require a capital investment. The gene technology checks every box. Our excitement in pursuing the décolleté in phase II is not only based on the strong data we saw in the cohort IV study, but our timing is perfect, as the décolleté has become an extension of the face, with today's designers showcasing the beauty of the female form in their deep, plunging necklines. We know the 4.5 million estimated aesthetic patients are requesting effective anti-aging treatments for this delicate and thin skin area that ages quicker than other areas of the skin. To date, the FDA has not approved any aesthetic injectables for this region, and off-label use is limited because of the unique challenges of treatments in this area of the skin. The current go-to treatments are lasers, but they inflict injury to the skin in the hopes of producing neocollagenesis. KB301 is the ideal treatment to address the aged and pigmented skin by using the body's own natural production of collagen, and the décolleté is the perfect canvas for our first product candidate. In addition to the significant demand from current aesthetic patients, there are market expansion trends that promise to swell the numbers of patients seeking to rejuvenate their skin. First, the global population spent $25 billion on skin rejuvenation products and services in 2023. KB301 will appeal to the consumers who to date, have only purchased over-the-counter topical creams. KB301's non-invasive and natural-looking results provide the skin rejuvenation solutions that this market segment is seeking. Next, demand for minimally invasive procedures, such as neurotoxin and filler injections, is on the rise in younger demographics, including a reported 50% increase between 2015 and 2020 in the millennial age bracket, and aesthetic treatments are even more accepted and pursued by the Gen Z population in their twenties. Both the millennials and Gen Z generations believe in prejuvenation, which is treating the skin prior to when wrinkles and pigment issues arise. They are actively looking for non-invasive, natural-looking skin rejuvenation treatments, and lastly, and most recently, the Ozempic face has become a concern following rapid weight loss. Plastic surgeons have reported that their patients who have lost weight with a GLP-1 have accelerated aging of their skin, making surgical procedures more challenging. KB301 could be used to rebuild the skin prior to or in place of a plastic surgical procedure. We believe that the existing aesthetic patients will quickly incorporate KB301 into their treatment cycles of neurotoxin and fillers. We also believe that consumers who have not advanced beyond over-the-counter lotion will seek out providers for the natural-looking skin rejuvenation provided by KB301, thereby making it their first and only choice in non-invasive aesthetic treatments. Using conservative estimates, we believe the skin rejuvenation market will be in line with the neurotoxin and filler markets as the primary tool for skin rejuvenation. And now, I would like to hand the presentation back to Krish. Thank you, September. We're looking forward to progressing KB301 into phase II next year. This is not, however, the only active program at Jeune. Our vector platform is amenable to the delivery of various payloads, including other extracellular matrix proteins that are high priorities in the field of aesthetics. In addition to our KB301 asset, I will highlight our KB303 program, designed to deliver elastin to the skin. In preclinical studies, we've already demonstrated that we can achieve robust elastin expression, and that elastin produced in vivo organizes and fibrous, which is a requirement to impact the elasticity of skin. With this program and others, Jeune is poised to deliver a comprehensive offering in the field of rejuvenative aesthetics. Finally, I will touch briefly on our long-term strategic vision for Jeune. Krystal is well-positioned to advance KB301 in the near term. Managing regulatory interactions, manufacturing, and phase II setup are well within our areas of expertise. However, we recognize that as KB301 progresses in the clinic, the need for dedicated resources and commercial aesthetics expertise will grow. Jeune was purpose-built as a wholly owned subsidiary to allow optionality for spin-out or a partnership during clinical development. And as we progress through key value-creating phase II milestones, we will leverage this optionality to ensure that Jeune is optimally positioned to deliver on our vision of creating a new segment in medical aesthetics. And now, operator, we'd like to open the line to questions. Thank you. At this time, we'll be conducting a question-and-answer session. As a reminder, during the question-and-answer session, there will be a limit of two questions per participant. If you have any questions or comments, please press star one on your phone at this time. We ask that while posing your question, you please pick up your handset if listening on speaker phone to provide optimum sound quality. Once again, please press star one on your phone at this time if you wish to ask a question, and please hold while we pull for questions, and the first question today is coming from Alec Stranahan from Bank of America. Alex, your line is live. Hey, guys. Thanks for taking our questions. Just a couple from us. First, maybe thinking about how FDA might advise your approach to a phase II study. Maybe walk us through any regulatory precedent for percent of subjects achieving either a one or two point improvement that it might be viewed as meaningful. Do you think, you know, Juvederm or Kybella might be appropriate analogs here? And then I've got a follow-up. Thank you. Hey, thanks. Thanks, Alex, for the question. This is Krish. You have to realize we primarily go through OTP and not the derm division as some of the other aesthetics drugs have gone through. So that's an important distinction that is tough to, like, elucidate completely at this point. But the general feeling, if you look at a prior approval of LaViv, could potentially be a bit faster, sooner than a classic approval in the aesthetics area. So in terms of phase II, I want to be clear, we haven't really yet, we have yet to meet with the FDA. But our expectation is that we enroll about 80-120 patients in a phase II study, and then figure out what the path forward is at that point. But ahead of just presenting a protocol for the phase II, we have to complete a scale development based on what we've seen to date, based on the pictures, all the different pictures and the improvements. We'll work closely with Yoelin and whoever and other investigators to kind of develop a comprehensive scale and move forward. Scale development usually doesn't take that long. It's about three to four months once we get started, maybe even less. And so we feel pretty good about getting the study going next year. Okay, that's helpful. Then, you know, maybe appreciate the, you know, the update on the indication that you'll be pursuing. Maybe as a follow-up, talk about any precedent paths for label expansion, say, beyond the dystrophic EB, if approved. Thank you. September? Sure. So the concept that we are pursuing is to focus on a single indication for KB301, and then to extend the pipeline forward with an indication for our next product candidate. With regard to product extensions in the aesthetic space, we're very aware that products are used all over the body once they're approved. So, basically, our opportunity is to expand the product pipeline as quickly as possible. That's the way that we're thinking about it. Understood. Thank you. Thank you. The next question will be from Tim Lugo from William Blair. Tim, your line is live. Hi, team. This is John on for Tim. Thanks so much for taking our questions. So could you provide us some color on how the GAIS scale compares to some of the other aesthetic scales, such as those that are more specific to lateral canthal lines? And then maybe as a follow-up, could you give us any details on any FDA interactions you've had on that scale, and how you're thinking about potential for just using that in the phase II study? Sure. So I'll start with the GAIS. That is basically it allows the investigators and the subjects to compare the improvement relative to baseline, whereas your scales that are developed for your primary endpoint in the phase II, phase III studies are actual grading scales that the investigator and the subjects use to assess the scale at a specific time point. So typically, what you see in the phase II, phase III studies is your primary endpoint using these specific scales, but they also as an exploratory secondary endpoint, collect the GAIS because it is very informative with regard to subject and investigator satisfaction. And with respect to the FDA conversation, I think our path forward is to develop scales specific to décolleté based on what we've seen on KB301, and along with GAIS, present both scales and get an acceptance before we actually lay out the phase II protocol. Very helpful. Thanks. Thank you. The next question is from Ritu Baral from TD Cowen. Ritu, your line is live. Hi, guys. Thanks for taking the question. I wanted to dig into the scale development just a little further. So it sounds like it's not gonna be a derivative of GAIS or even the FSO. Can you talk about the elements that you may propose, or at least that makes sense to go into that scale? I noticed you guys mentioned pigmentation in one of the patients. Is skin thickness part of this discussion? I know the data that was presented was just knee, but if you could walk us through that, and then I've got a manufacturing question as follow-up. Thank you. Sure. I'll take the scale development question. So it is very specific to cutaneous wrinkles. So we will have a five-point scale that it's essentially a descriptive and also an image for every step in that five points that allows the physician and also the subject to do an assessment of the subject at that given point in time and determine where they are on that scale. So it is not reflective of pigmentation. It's not reflective of skin thickness. All those are exploratory data points that we can co-collect in the phase two and the pivotal studies. But as far as our primary indication, it will be the classic scale, looking specifically at cutaneous wrinkle improvement. Understood. And then on manufacturing, can you say where you are on CMC? Will you be going into phase II with, you know, registrational ready product? And where do you plan on manufacturing it? Mostly ASTRA, or are you gonna do some of this at Ancoris? Thanks. Yeah, thanks, Ritu. To answer the second part of your question, yes, ASTRA is fully capable of supplying the demand based on our initial forecast at this moment. In terms of actually scale-up, I alluded to this in the Bristol call. We're starting a process of scale-up and scale-out activities. We're very cognizant of the price point in aesthetics compared to the price point in rare diseases, and feel really good about a potential margin in aesthetics that we're comfortable moving the program forward. Will the phase II product be phase III and registrational product? I'm sorry, I didn't hear you. Can you repeat the question? Will the products that you use in the phase II trial, will it be, registrational quality CMC wise? Yeah. Yes, they will be. Got it. Thank you. Thank you. The next question will be from Dae Gon Ha, from Stifel. Dae Gon, your line is live. Great. Good afternoon. Thanks for taking our questions. I guess, a question for Dr. Yoelin. When we look at the data, it seems like, you know, in the case of the décolleté, you've got 28% at month one, improving by two points, and then 28% also improving by two points, in month two. I just wanted to clarify, does that mean it's the same patient population that had maintained the two-point improvement at month one and persisted out to month two? Or were there differences there, some new and some dropping out of that two-point scale? And then maybe the, the question for the team. When we look at the GAIS, between the investigator and the subject assessed, I guess, there is obviously going to be some, variability between the two. Which one should be the most important as you kind of approach the FDA discussions, and would SSQ or any other PROs be important to substantiate that type of a primary endpoint? Thanks so much. Dr. Yoelin? So I think the question was, at month one, there was a 28% reported two-grade improvement, and at the two-month mark, that was the case as well. And, you know, unfortunately, I don't have that data set in front of me, so it's really hard to know if those individuals that experienced a two-point improvement went on from the one-month mark to the two-month mark to experience that, or there was a little shifting in terms of if there was, you know, someone who may have dropped off a little bit, and then the individuals who only had a one grade experienced it at the one-month, experienced a two grade at the two-month mark. So unfortunately, I don't have that data in front of me, but perhaps September or Krish, do you have that data in front of you so you can answer the question more granularly? Absolutely. It was very similar to what we saw with cohort II, specifically in the durability study, that when they peak, it is plateaued, and it's maintained, so it is 28% that was peaked at two points at one month and continued out to two points or continued out to two months, maintaining at two points. Thank you. Sure! And with regard to the GIAS and thinking about, you know, what carries more weight, the investigator or the subject, they're both very indicative of the feedback and the satisfaction levels, and obviously, both are very important. I can tell you, 'cause you referenced GIAS and primary endpoint, the GIAS won't be a primary endpoint for the phase II. It will be the scale, the scale that we were talking about. GIAS will be secondary, but we know from research that this positive GIAS scores that we're seeing is indicative of what we will see in the scales, once we have them developed for phase II. Okay, thanks very much for the clarification. Yeah. Thank you. And the next question will be from Tolani Othman, from Goldman Sachs. Tolani, your line is live. Hi, all. This is Tolani on for Andrea. Thanks for taking our questions. First, can you provide a little more color on what was driving patients' decisions to redose? So, you know, what proportion of them opted in, and how are you thinking about real-world utilization of KB301 in the context of redosing and long-term benefit? Then I have a second on the market opportunity afterwards. Thank you. So redose, we had three doses that were universally supplied for both cohort III and cohort IV. In cohort IV, we did have, and it's still underway, a optional retreatment, and of these 18 subjects, 13 opted to continue into the retreatment. We are kind of in the middle of summer, and there were vacations and scheduling issues that limited the you know some of the patients in continuing on to the optional retreatment, but it was a very positive overall. Everyone wanted it, but not everyone could participate 'cause of their schedules. Okay, that's helpful. Thank you. And then the second one, how are you thinking about the longer-term market opportunity for KB301, specifically in dynamic wrinkles of the décolleté, especially in the context of existing therapeutic options? So for example, Botox, other injectables and serums, which may be used off label. If you could share a little more on that as well. Yeah, I'll start, and then I'll turn it over to Dr. Yoelin. In the décolleté area, the wrinkles that you see are called cutaneous wrinkles, which are wrinkles of the skin. Typically, when you use a filler or a neuromodulator, you are looking at an area that has lost fat or has lost bone due to natural aging. That would be where you would use a filler, typically, and then a neuromodulator if the wrinkle is formed by a muscle contraction. But what you see in the décolleté is really cutaneous wrinkles, so it's wrinkles of the skin. So the primary tool that are used are lasers, and they inflict damage to the skin, hoping for neocollagenesis, which is essentially the rebuilding of collagen. But it's challenging to use a laser because you have different Fitzpatrick or different colors of skin, and sometimes you can cause hypo, hyperpigmentation of the skin. So there's a lot of variability in using lasers based on the technology and also on the patient. Dr. Yoelin, do you want to add any color to that? Yeah. It's actually a great question. And a little bit of background about me. I'm an ophthalmologist, as was described earlier, but for the past twenty-five years, all I've been doing is injecting things like neurotoxins, Botox being one of them, among all the others, the serotypes that are approved here in the States, and then also the HA dermal fillers and the biostimulatory agents like Radiesse and Sculptra. And I think one of the significant downfalls, and you can use neurotoxins in the décolleté, and we use them not so much for the dynamic piece, but we use it for improving skin quality. But it's expensive, and it's not very long-lasting, so a lot of people don't really use neurotoxins to improve skin quality in décolleté or décolletage. Then you're left with the HA dermal fillers, which do, I think, a reasonable job, but basically, they're not adequate, and I think that's why a lot of us have sort of turned away from HA dermal fillers in the décolleté or décolletage, and so we're left with these biostimulatory agents. Once again, a lot of us don't feel super comfortable with the fact that the products don't work as well as we would want them to, and they don't meet patient expectations. There's this massive opportunity, and there's also this desire to use more of a natural way to improve the quality of our faces and our overall skin. That's why this, you know, gene therapy, which is what I think of when I think of what we're talking about this afternoon, is so vitally important, and there's this massive abyss, if you will, or void, where we just don't have anything. It's one of the things that we literally want, but we just don't have. So the opportunity here for, you know, rejuvenation of the décolleté, not just with, you know, Collagen III, has been mentioned before, but elastin represents this massive opportunity, and I actually think it will eclipse the neurotoxin marketplace across the board, and even the dermal filler and collagen stimulator marketplace, the biostimulatory agents. And the reason I say that is, while the face is important and it's high-value real estate, compared to the body, it's very small. I mean, the body is so much more massive. And if all we need is one indication, like what was discussed earlier in the décolleté, and then we'll start using our creative senses, practitioners will, and we'll be using this product, I would imagine, all over the body, whether it's the neck, the face, the extremities, or the trunk. And so the world is really hungry now just on the practitioner side, but the patient side, for something like this, gene therapy, true regenerative medicine, because we're just not there yet. We desire to be there aesthetically, but we're just not. So I think the opportunity here is just absolutely immense, especially for someone like me, who does not rely on devices. I just rely on injectables, and unfortunately, kind of fallen short so far up until this point in time. And I know I kind of went off a little bit, but I'm pretty excited about the opportunity of working at the gene level to improve the quality of our patient's skin, not just the face or the décolleté, but the whole body. Thank you so much. Appreciate it. Just one more, if I may Of course. A follow-up to my earlier question. For those patients who did opt for the retreatment, so those 13 patients that decided to go ahead, was there a specific reason behind their choice to go ahead with the retreatment? And what frequency of those would you expect in a real-world setting? Yeah, I can take that. I can- Oh, no, go ahead, Dr. Yoelin. No, people, it's really interesting because the vast majority, I think there are two sites in this study, but in our site, people will do anything to improve the quality of their skin, and I practice in Southern California, and a lot of my patients have fairer skin, and as I said before, there really is very little, if anything, that can be done for the décolleté or décolletage to meet the needs of these patients, so it's very promising that individuals, first of all, enrolled in this study, and we didn't have a hard time at all getting people to enroll, but when people re-enroll and they want to continue, it speaks volumes in terms of the potential of a product. I've done probably 70 clinical trials over the course of my career, and the patient-reported outcome piece is very important. But what's probably more important is what you just mentioned, is the level of enthusiasm of re-enrolling or continuing to be treated. And these treatments, you know, being poked by a needle is no fun, but people are willing to take on that discomfort in order to make sure that they get a result. So there was a fair amount of enthusiasm, as what September talked about. It is in the middle of summer, and people do vacation. We require them to be, you know, very prudent with regards to our appointments. But to get this kind of re-enrollment, if you will, is a very big deal. It speaks volumes in terms of the desire to look their very best, but also the fact that the product works. Makes sense. Thanks, Doctor. Oh, sure. It's Steve. Thank you, and once again, it will be star one on your phones at this time if you wish to ask a question today. That's star one if you wish to ask a question. The next question is coming from Geulah Livshits from Chardan. Your line is live. Good afternoon, and thanks for taking questions. Maybe sticking on the topic of dosing frequency and redosing, can you talk about what kind of dosing frequency is considered attractive? For example, again, in comparison to the frequency of laser use, and also kind of in a somewhat related note, what kind of duration or follow-up do you expect the FDA would want to see from, you know, phase II and ultimately, a clinical program? Thanks. Yeah. So thank you for the question. With regard to dose, so we, both in the cohort II study and the cohort III study, we did three treatments, and then we followed the patients. So in the cohort II study, we followed them for an initial three consecutive months, and then we did an extension where we followed them out through to nine months after their dosage. And so we saw, you know, peak efficacy and then maintaining it out to nine months, which is very unique. What you see typically with a neurotoxin or a filler is that there is a bell curve, and at some point you start to see the return to baseline. Mm-hmm. But with our product in cohort II, we didn't see that. So with the cohort III and cohort IV, we took them out to two months because we wanted to collect that data and knowing from our cohort II experience, that they would reach peak efficacy in that period of time. So we do expect to see the same sort of duration that we've seen so far in our cohort II, without a return to baseline, so meaning that it could extend longer than that time period. Mm-hmm. And then with regard to what the regulators would want to see in terms of follow-up? I'm sorry. So with regard to what the FDA would want to see in terms of follow-up? Yeah. Yeah. So we actually haven't had those conversations with regard to duration, but we're thinking probably following them for about six months. You mean post-approval follow-up? No, just in terms of, kind of understanding the overall package, in terms of the kinetics of the activity and safety and things of that nature. Right. I mean, our expectation is maybe patients get, like, two doses a year, based on the durability we have seen. But I thought where you were going was once approved, like, you know how in Vyjuvek, we follow the patients for a certain amount of time for safety reasons, post-approval? What we were trying to say is that we haven't gotten to that point with the agency, but we don't expect it to be any different than what- Mm-hmm. KB103 or Vyjuvek is going through. But in terms of, like, dosing frequency, we're probably, you know, at this point, thinking, like, two doses a year, depending on what we see. And that's kind of how we are thinking about designing the phase II. Got it. Thanks. That's helpful. Thank you, and the next question is coming from Yigal Nochomovitz from Citigroup. Yigal, your line is live. Yeah, hi. Thanks. I'm just going back to an earlier comment from the physician. You know, once you get an initial label for the décolleté, you know, given the, as was mentioned, the sort of creativity in terms of using this product in different parts of the body, on the lateral lines and so forth, you know, how much of a driver really is there to have a an expanded set of indications? Once you're on the market, it seems like this product will be used liberally in different ways, you know, as is determined to be suitable for a patient, you know, on a case-by-case basis. So just, c an you talk about, like, how many indications you actually need to have out there before the product just sort of, you know, takes on a life of its own? And thank you for that question. It's actually a great question because I'm thinking about, you know, for example, Botox, you know, more recently, Xeomin, and Botox. Its first aesthetic indication was for glabellar lines. And for many years, obviously, we used it in the glabellar. I think it was back in two thousand and two is when Allergan got that indication. And we moved to the high forehead, we moved to the lateral canthal lines, we moved to the masseter, we moved to mentalis, we moved to orbicularis oris, we moved to the neck. We kind of moved around, determining kind of where the product would work the best in our practices without, you know, an FDA indication. As time has gone on, what Allergan has done, and to their credit, and they've spent a lot of money doing this, is they pursued some of these other areas in order to give us a better idea of how best to use the, their particular product in these areas, so that there'd be a way in which maybe newer injectors or even more seasoned injectors, could kind of lean on a way, or I could say, look to an indication and look at the way in which that indication came to be and mimic that injection pattern based on what was in the clinical trial. So what I would say is, while it's true, I think it's important to let the market sort of decide what might be sort of the next best area or areas, but eventually, I think that using the information that the company will gather from that quote, unquote, "off-label use," if you will, to create algorithms for different areas of the body or the face, makes a lot of sense in terms of helping newer injectors, as I said before, even more seasoned injectors, get best results possible. So I think that what you say makes complete sense. You just ideally need one indication, and that indication is probably décolleté or décolletage. But once that's awarded to the, you know, the manufacturer, then it would be sort of up to the clinicians to decide maybe what works best, using, you know, a technique that they think about, and then that information then is shared with the manufacturer, and then the manufacturer then can move forward in terms of what may be best. I know that's a very long answer, but that's, The Botox example would be a really nice way to think about what lies ahead for the company. Got it. Thank you. Of course. Thank you. And that does conclude today's Q&A session. And also, this concludes today's conference call. You may disconnect your lines at this time, and have a wonderful day. Thank you for your participation. Thanks, everybody.