Good day, and thank you for standing by. Welcome to Rhythm Pharmaceuticals, Obesity Week 2023 data presentation. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question -and -answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Mr. David Connolly, Head of Investor Relations and Corporate Communications. Please go ahead. Thank you, Norma, and thank you everybody for joining us today. For those of you participating via the conference call, there are accompanying slides that can be accessed and controlled by going to the events section of our Investors page on our website at ir.rhythmpharma.com. Yesterday in the afternoon, we announced data from our long-term extension study evaluating setmelanotide in patients with hypothalamic obesity and additional data, which were presented at the Obesity Society's Obesity Week conference in Dallas. This press release and the data presentations are now available on our website. On the conference call today, we'll hear from Dr. David Meeker, Rhythm's Chair, Chief Executive Officer, and President, and Hunter Smith, our CFO, will join us for Q&A. Now, moving to slide three, I'll remind you that this call contains remarks concerning future expectations, plans, and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly report on file with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to David, who will begin on slide four. Thank you, Dave, and thanks to all of you for joining this morning. So we are coming off a very good TOS meeting in Dallas, where we held two advisory board meetings. One discussing hyperphagia, an incredibly important aspect of these diseases that we know is highly debilitating, not only for the patient, where it can decrease their ability to concentrate and function, but for family members living with that severe preoccupation with food and the associated behaviors. The second advisory board discussed the importance of getting to a diagnosis of BBS and the role genetics might play in that effort. So there's more to come in these areas as we go forward. We had six data presentations, as you can see on slide four. Two reflected some early work trying to understand how treatment can modify future cardiac risk. That's obviously challenging to do, and when you're working with such small cohorts. But, but the effort or the exercise was supportive of the obvious point that early and effective intervention is probably good in terms of modifying one's subsequent or future risk. Second, we looked at the long-term maintenance of BMI reduction in both POMC patients and BBS, showing the sustained effects of setmelanotide treatment. The nine BBS adult patients achieved a mean BMI reduction of 16%, and the 15 BBS pediatric patients achieved a reduction of 0.7 in their BMI z-score. In patients with POMC and LEPR deficiency, we showed a BMI reduction of 20.3% in 11 adult patients and a 1.2 reduction in their mean BMI z-scores for patients younger than 18 after four years of setmelanotide therapy. Both of these results highlight the durable effect of long-term treatment. So now let's move to the 12-month data on our long-term extension hypothalamic obesity patient cohort, which is obviously data that we are quite excited about. So on slide six, you can see this is the disposition slide we've shown many times. Out of 18 patients who entered the original study, 14 went on to enter the long-term extension, and we're reporting here the full 12-month data set for the 12, who, from whom we have, 12 months of data. But we do have the updated data from the other two patients who do not have a full 12 months, but you can see their course. And so importantly, we have not lost anyone in our long-term extension. On slide seven, we have the demographics. These are the baseline characteristics of all 14 patients. Their mean age was 13.6 years. Eleven of these patients had a craniopharyngioma. Not surprising, as that is the most common cause for patients who go on to develop hypothalamic obesity. Two had hemangioblastomas and one had an astrocytoma. The mean BMI for all patients was 37, with a mean BMI z for pediatric and adolescent patients of 2.5. For the 95th percentile, let me provide a little bit of context, because this may not be a measure that everyone's familiar with, but it is becoming a preferred measure for evaluating weight in patients under the age of 18. So for each patient, their BMI is divided by the BMI value at the 95th percentile for that patient's age and sex. For example, if the 95th percentile BMI value is 25 kilograms per meter squared, and the patient's BMI is 30 kilograms per meter squared, the patient's BMI would be 120% of the 95th percentile or 1.2 times the 95th percentile. So what you see here is these patients had, at baseline, a 145.3% of the 95th percentile at baseline for these 11 pediatric patients. So moving to slide eight, we have the efficacy data. In patients on setmelanotide therapy achieved a BMI reduction of 17.7% at 16 weeks, 23.4% at 6 months, and 25.5% at one year. And it's important to remember when you're looking at the BMI data, that and we had children, younger kids under the age of 12 in the trial, that you would expect BMI to increase naturally as these children grow. So you're trying to help them reduce their BMI to get them back in a more normal range. But you also have physiology, which is, you know, working as a, you know, return to health. That should be, BMI should be increasing, and we have some of the patients who are in the normal range whose BMI is increasing. So the mean value is confounded by that fact. When we look at the more age-focused measures for patients younger than 18, we see a reduction in their BMI z-score from 2.5 to 1.5, and a reduction of their ninety-fifth percentile from 145.3 to 104.5. So the overall effect continues to be quite, quite strong. On slide nine, you see the waterfall plot showing the 16-week and 12-month data, which shows that essentially all patients are showing further deepening or maintenance of an early, very strong response. And I'll come back to discuss the two patients with a more modest effect, who are at the far right-hand side of the slide in the upcoming couple of slides. So on slide 10, and this is the spaghetti plot. In slide 10, the spaghetti plot highlights the fact that patients, some patients do plateau, as you would expect in theory, once they get back to their physiologic set point, which may or may not be a value in the normal range. That a number of patients who may not have reached that set point continue to trend down. I want to highlight the patient in the light blue line. It's that top dot on the spaghetti plot there, who had lost approximately 13% of their BMI from baseline at 16 weeks, but had now increased to still well below their baseline, but now minus 7% from baseline. So this is an 11-year-old patient at trial start, peripubertal male, who as best we know, had been compliant with his medication, but did have a relaxation in their healthy eating habits after getting on the drug and having a good response, and that this was associated with an increase in BMI. How the additional physiologic changes that he was experiencing impacted, again, a little less clear. But, the drug's not magic, and, clearly if you adopt eating habits that are not so healthy, you know, you're not protected from potential weight gain in that setting. The other patient we will discuss on the next slide was the 12-year-old patient with a hamartoma. And that was the one patient out of the 18 patients who was compliant with their medications but failed to lose 10% or more at 16 weeks. So before we leave this slide, I do want to highlight the two patients who are intermittently off treatment. So we do not have full 12 months of data, but we have their data to the current point. And the first patient in that panel had a very robust initial response, losing 21% of their BMI at 16 weeks. Although he entered the long-term extension, he was immediately lost to follow-up. When he was relocated and reentered into the trial, he had regained all of his original weight. The patient had been slowly titrated up again, and as you can see here now, as he's back on medicine with an increase in dose, his BMI is now down 11% from baseline. The second patient is a patient who'd struggled with gastrointestinal complaints prior to entering the study and has had difficulty with nausea throughout her experience there. And so she's been literally up and down on her dose and occasionally off her dose. And so when her dose was increased, she lost weight. When it was decreased, she regained. She's now back on treatment and, as per the investigator, very happy to be back on treatment. So both of these patients are valuable in highlighting the importance of continuing the medication and showing the on-off effect here. So moving to slide 11. Slide 11 shows the follow-up DEXA data, where again, for the majority of patients, you can see a further decrease in fat mass, shown in green, with a much smaller decrease in lean body mass. Patient number six, in the middle of the slide, is the 12-year-old patient with that very modest decrease in BMI relative to the others, although it has slowly and steadily come down. And that patient now is about 8.9% decrease in their BMI. And if you look at the DEXA results. Sorry, 8.7. Apologize for that. If you look at that patient's DEXA results, you'll see at 16 weeks, had an almost 10% decrease in fat mass, with a 17% increase in lean body mass. This pattern has further improved at his follow-up scan, with a 15% decrease in fat mass and a 24% increase in lean body mass. So in light of that full data picture, he's actually having an incredibly healthy response to the drug and actually may have, paradoxically, been one of our better clinical responders overall. So now moving to slide 12. You can see the positive shifts in obesity classifications, with all patients moving by one or more classes. Three of the patients are actually now in the normal range, below the 85th percentile, and an additional two are below the 95th percentile, whereby that criteria, they would not have been eligible to enter the trial. So on slide 13, this is just a reminder of how important this program is, not only for the patients who do not have an approved therapy, which reliably works, but obviously for Rhythm as well. The U.S. prevalence numbers are in the range of 5,000-10,000, with the unusual element, as we've highlighted previously, for a rare disease, that the vast majority of this population are diagnosed and engaged with the healthcare system. And finally, on slide 14, the phase III trial is ongoing. We're making good progress towards our goal of full enrollment by the end of the year. And with that, I will open it up to questions. Thank you. As a reminder, to ask a question, you'll need to press star one one on your telephone. To withdraw your question, please press star one one again. Please wait for your name to be announced. Please stand by while we compile a Q&A roster. One moment for our first question, please. First question will come from the line of Tazeen Ahmad from Bank of America. Your line is now open. Hi, guys. Good morning. Thanks so much for taking my question, and congrats on the updated data. David, I just wanted to ask your thoughts. As you see, you know, the maturing of data for the HO population, how should we be thinking about some points about differentiation from the GLPs, which some doctors might still feel might be a first-line therapy for some of these patients? And also, just based on what you said about that one patient that might not have kept to their healthy diet, is there a difference in the level of hunger that patients who are HO feel relative to other MC4 defective patients who've received the drug thus far? Thanks. Yeah. So let me take the GLPs first, which will be an eternal question here. I think I'm gonna refer you, remind you of Dr. Abuzzahab quote, who we had on the very first analyst call that when we presented the initial data. And, you know, what she has highlighted is that she thinks on the order of about 20% of patients with HO will have some response to a GLP. And the magnitude of that response would be on the order of 10% or less. And as I've said many times, pressure tested that with other experts in the field, and that resonates with them. If anything, they think that may be a little high, not low. There was a recent abstract at the ESPE meeting, you know, European Society of Pediatric Endocrinology in Europe, and where they looked at three to six patients and who had been on either liraglutide or semaglutide. And they fit that pattern, where they had an arresting of their weight gain. I think the maximum decrease they reported was about 8% in one of the patients there. So people gain weight for different reasons. The GLPs and these combo therapies, you know, are incredibly powerful and good drugs. And so, you know, putting a patient on these drugs, you may, you know, and not uncommonly, get some weight loss. I think what's pretty clear is that one, you're not getting this kind of an effect. So, you know, hopefully this kind of data will increasingly highlight the difference in why what we're doing, replacing the missing hormone, in theory, is getting at the fundamental problem here. Whereas, you know, the other GLPs or approaches, any other medication may be working indirectly in terms of trying to modify this problem. And the other piece is, liraglutide has been out since 2014, and it's available, some may not be quite as good a drug as semaglutide, but it's a good drug. And the number of reports that that works and has been effective, they're extremely limited. So again, if it was magically correcting the problem, people would go there. So, that question will continue to come up, but I think, you know, the more data we can put out, and, you know, obviously the phase III trial should be highly supportive. Again, I feel that people will increasingly understand that this may be the root cause of that problem. And then your question was on diet, or sort of how they experience hunger. And the HO patients, what's interesting here is it is a little bit different, and part of that may have to do with the genetic causes, have a surgical interruption, if you will, a very specific, no, surgical is the wrong word. They have a very specific impairment of the MC4 pathway without damage to the other parts of the hypothalamus. Whereas in the HO patient, they're getting various amounts of one trauma, I mean, to the hypothalamus, and so other circuits, to a variable degree, can be affected. So the picture is, I would say, much more heterogeneous. Not all patients complain of hunger in exactly the same way. But in our phase II trial, we collected hunger scores, and even those patients who started with a lower hunger score, they had a very significant decrease in their hunger from wherever they started. So there's no question that a decrease in hunger, as measured by those scales, this lack of inability to feel full, that is being addressed and is playing a significant role here, along with the fact, in theory, that we're also significantly increasing the energy expenditure to get these kind of reductions in their overall BMI. Okay. Thank you. Thanks. Thank you. Next question? Thank you. One moment for our next question, please. Our next question comes from the line of Phil Nadeau with TD Cowen. Your line is now open. Good morning, and congratulations on the data, and thanks for taking our questions. One question, a follow-up on the hunger score. I think you showed a 45% mean decrease in maximal hunger at week 16. How did that trend over time out to one year? Was that relatively consistent, so the hunger went down and stayed down? Was there some fluctuation? Did the maximal hunger score continue to decrease as weight went down? What was the trend line in the hunger for most patients? Yeah, it's a good question. So we haven't continued to follow the long-term extension data. We collect slightly different things, so I don't have that data. But the good news is, the indirect measure of that, which is the BMI, would suggest these kids are obviously doing much better, continue to do much better. I think, you know, part of what's been described is that these kids are returning—most of my kids are returning to more normal states which they were before, in a more normal relationship with food. And that's not just the HO population we're hearing from. This is the BBS, the POMC world. You know, it's a very different thing than just I have no desire to eat. It's that, you know, suddenly, it's not that I lose completely my appetite, but I feel full. I eat a meal, I feel full, I get up from the table, I leave food on the table. So, you know, that, that is the nature of what I think people are experiencing. But to your specific question, Phil, I don't have the long-term numbers for under on this group. Got it. Okay, and then second question is on the plateauing. Where did the plateauing of weight tend to occur? I know you said it didn't necessarily mean patients go back to normal, but they get back to maybe their normal physiological set point. So was the plateauing of weight largely in the five patients who got to overweight or normal weight categories? Or was there actually some plateauing for patients who were still classified as obese, even at week 52? Yeah, I think, so it'll be interesting to see how this plays out. If you go back, and I hope my number is correct here, and look at slide 11, with the spaghetti plots. You know, the kids or the individuals who are getting down with their 35%-40%, although some of those are still trending down, I think they're, you know, getting—those are part of the group that's getting into their normal range. But the upper group, as I said, this doesn't... Your normal—Before you get your tumor, if you were an overweight individual before you had your craniopharyngioma and developed HO, this drug, in theory, could get you back to that prior overweight state, but doesn't necessarily allow you to then fall below that. Got it. Okay. Congrats again on the data, and thanks for taking our questions. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Derek Archila with Wells Fargo. Your line is open. Great. Thanks, and good morning, everyone. Thanks for taking the questions. Just two from us. First on HO, maybe just discuss the change in AE rates that you saw, you know, between the index trial and the long-term extension. You know, mainly hyperpigmentation and some of the GI-related side effects. It looks like those rates went down pretty meaningfully. And then also, you know, on the Bardet-Biedl three-year data, I guess, how do you think that's gonna impact the ongoing launch? I mean, have doctors and some of the caregivers been looking for longer-term data before putting their patients or, you know, their kids on Imcivree? So again, you know, is that something that you think will impact the launch positively? Thanks. Yep. So in the AE rates, the, as you highlighted, those are the two areas, hyperpigmentation and the GI effects. Hyperpigmentation, just a reminder, I mean, it- because it's an on-target effect, meaning- or an off-target, on-target, meaning this drug hits the MC1 receptor, every patient will have some change in their pigmentation. It's just that if you're very fair-skinned, that change may be very light and not noticeable. In fact, you know, for many patients we've heard it, they like it. But for the darker you are, the, you know, more melanin you release in this, and, and that, that may be more noticeable. So the reporting of it's highly variable across our, our studies, but it, and it occurs relatively early, so that'll be captured relatively early. That's a one-time event. You know, you get it, you don't get it, you report it, you don't report it. The GI complaints, again, what was reassuring is that this drug is very well behaved. I mean, I think as we begin to study it more and across, you know, different populations, the pattern of the adverse event profile is very consistent. So the GI complaints, the nausea, rarely vomiting, but, you know, those two, they occur early. They tend to occur in the first few weeks of treatment. They can be managed by taking longer to dose escalate, or if you need to, even going down a dose and continuing for a longer period before you dose escalate. So, this has stayed exactly that way. And then to your point, as you get out into, you know, beyond the three-month point, the GI complaints become negligible. You know, as a rule, with the exception, I highlighted that one patient who continued to struggle throughout the trial. But as a rule, they tend not to be an issue beyond that very early stage. Your question around the BBS data. Yeah, I think, you know, this all builds. In a rare disease world, I think, is rarely one piece of data or one event that, you know, dramatically changes the overall picture, but this is highly encouraging. And the fact that, you know, you go on the drug, and if you stay on the drug, you can maintain or continue to lose weight and decrease your overall BMI. And that is consistent with how we think about this, which is unlike a lot of interventions where you're pharmacologically manipulating a situation, you're taking a normal state and trying to disrupt it to get a benefit in another way. We're, in theory, replacing a missing hormone, this alpha melanocyte-stimulating hormone, which is low or absent in these patients who we're studying. And so once that signal's been replaced, then, you know, that should be a more normal, more physiologic state, and that may be a more durable kind of intervention, and that's what I think this data suggests. Got it. Thanks, David. So how would it affect the launch? Yeah, I, I don't know. the launch? Yeah, I, I don't know. Congrats on the data. Obviously like I said, all good news is good news, and I think it'll help us, but I'm not expecting an avalanche of response in the next two weeks. No. Got it. Thanks. Thank you. One moment for our next question. Our next question comes from the line of Dae Gon Ha with Stifel. Your line is now open. Hey, good morning, guys. Congrats on the data, and thanks for taking our questions. Two from us, both on HO. So David, if we go back to, excuse me, the Endo presentation in mid-June, and then compare that weight class data from then versus the Obesity Week presentation, it seems like the select guys are kind of in that similar BMI reduction. We haven't really seen additional gain on BMI reduction magnitude. So it does seem to kind of portray the plateauing and the reference you made earlier about pre-tumor weight may be kind of where they're sort of landing at. Can you just remind us, in terms of the LTE, do we have a longer-term follow-up, or are you planning on doing more updates just to kind of keep tabs on what might eventually happen to these individuals? Second, it's also kind of a multi-part question, but the DEXA data, I think it's pretty fascinating, you're seeing some lean muscle mass growth. There were a couple of tirzepatide presentations here at Obesity Week that started to look at sort of the leading causes or predictors of individuals that benefited more so than others. I think the cutoff was 30%. I know this data set you have is pretty small, but any insight you can glean from this that can be a predictor of who gains lean muscle mass? And would this be a potential differentiation versus GLP-1s? Thanks. Yeah. So your first question was just, will we continue to follow and monitor these patients? The answer is yes. They'll stay up until the drug's approved in a company-sponsored long-term extension trial. So we will continue to collect data, and we will update at some point here. We haven't guided as to when that will be necessarily, but we will, yes. And then two, in terms of the... I think the DEXA data is, of course, it's really incredibly interesting. I highlighted the kid with the hemangioblastoma, who, you know, we thought was having a more modest response, when in fact, you know, he actually looked like he may be having an incredible response here with, you know, and gaining the lean mass and then, you know, a little larger loss of his fat mass. Part of what makes the DEXA data challenging for us is, unlike a lot of the studies that are done in the patients with general obesity population, they can do large studies and very specifically isolate to adults and teens and, you know, ultimately children. But, we're having to mix them all together. And so we're trying to analyze data of kids, like I said, the whole peripubertal, you know, stage of life here, where we get changes in the body. You know, girls and boys have very different effects, again, as the hormones kick in and the like, and you're trying to interpret your data in that context. And so, that becomes challenging. But what's really encouraging here overall is that I think we have a pretty healthy basic response, which is, for the most part, we're losing much larger amounts of fat mass, than we are lean mass. The potential for gain in lean mass is definitely there, and this is something we're gonna follow, and the world's following it, right? Because, you know, shutting people's appetite down completely, is what's highlighted multiple times at the TOS meeting, isn't always good. And, you know, people get into other problems when that happens. So we're encouraged by this. Great. Thanks for taking our questions. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Michael Higgins with Ladenburg Thalmann. Your line is now open. Good morning, guys. Thanks for taking some questions. Congrats on all the data this fall. Two questions, if I could. In your ESPE presentation, you provided data from Roth and included variant classification in which genes are in your trials. But at your Analyst Day, when you provide Daybreak data, might you share that variant classification with the Daybreak data? Yes, the goal will be on the upcoming R&D Day. We will have a presentation on Daybreak, yes. Within that, would you share the variant classification for those handful of genes? Yes. Meaning in the pathogenicity state? Yes. When you say that, yes. Yeah, so to the extent that we have it, and, so for the genes we, we break out there, we'll, we'll provide as much information as we have to try to help everybody, understand what we've got. So yes. Okay, that'd be helpful. And then the second being, ahead of Daybreak, can you remind us the variant classifications, the pathogenicity state in your approved indications? So we, for POMC and LEPR, we're approved for, pathogenic, likely pathogenic, and the variant of unknown significance. And then for BBS, it's a clinical diagnosis, so it's not a, there is no genetics as part of it. The genetics are complicated and interesting, but they're not part of the diagnostic criteria as per the label. Appreciate that. Thanks, guys. Thank you. Thank you. One moment for our next question, please. Next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is now open. Yeah, good morning, everybody. Maybe just a couple from us. First, as you continue to get in these data, are there any additional baseline patient characteristics that you are seeing that are kind of influencing patients that have maybe greater or lesser magnitudes of response within the HO population? And kind of like, what are you seeing on that? And then the second one, on the patient six that you highlighted that had the increased lean muscle mass, do we know if there were some other, like, dietary or activity changes that influenced that? And can you remind us what the lifestyle modification recommendations are in this study versus in the ongoing phase III? Yeah. So just on that, I'll take that second question first. There are no lifestyle modifications. In most of our trials, we've done them without diet or exercise guidance. Our EMANATE trial does have a light touch on that, but it's hard to do and to do consistently and well. And second, it seems in most of our trials that our drug works independent of that. So no guidance in that sense. In terms of predicting, you know, which patients, here, it's just the data set's too small, right? I mean, it's a great question. I hope in our phase three, maybe we get some more insight. I don't know. You know, obvious questions are, if you've got somebody who's closer to when their tumor occurred, and so you're seeing the very acute effect of their weight gain, and you intervene shortly after that, could you more easily or, you know, to a greater degree, get back to their prior state as opposed to somebody who had it 10 years ago and maybe has settled in and has other confounding factors, right? All the things that cause any of us, the potential to gain weight. So, so anyway, those are, those are things we'll, we'll have a better sense, I think, coming out of our phase III trial. One follow-up, if I may, on that. You, you've talked a bit about patients kind of getting back to where they were prior to the tumor as the goal. So if they were already overweight, they get back to being overweight, but at least better. Do we have visibility on these patients, kind of pre-existing BMI before tumor? Or is that something you, have collected or have in this data? Yeah, we've done the best we could. It's all historical, and you go back and ask for their records, and they come in variable quality levels, if you will. But yes, to a certain extent. You know, one of the kids we've talked about, I mean, the six-year-old who had the most dramatic response immediately in the first 16 weeks, I mean, I think he was over 30%. You know, that child is gaining. His BMI is... He's below the 50th percentile, but his BMI is going up, so he's, you know, he looks great, normal. Okay, helpful. So your answer to your question was, do we have some insight to that? Yes. Thank you. Thank you. One moment for our next question, please. Our next question comes from the line of Joseph Stringer with Needham & Company. Your line is now open. Hi, good morning. Thanks for taking our question. Just a quick one from us. How has the compliance, in terms of missed injections, been tracking in the HO, OLE, and how does that compare to what was seen in BBS patients? So compliance overall, thanks, Joe. Compliance overall has been quite good. Again, in virtual, whether it's in a trial or in the real world, as best as we can assess. And, you know, we've attributed this in general to the fact that, you know, it's we're replacing a hormone. If you, when you replace it, you get that immediate signal, and people describe feeling different quite quickly. I mean, you know, whether it's that day or within a few days or a week, I mean, they recognize the difference of being on the drug. The compliance in the trial is very high. And I think, again, what the patients that I highlighted, those two patients who came on and off their drug, and this is, you know, patients recognize this. They come off their drug, and they immediately, you know, their course changes, and they go back to they're gaining weight and whatever their hunger state was, comes back. So, compliance has been high, and it's not just the fact that they're in a trial, but it's that the medicine, the signal itself, encourages high compliance. Great. Thank you for taking our question. Thank you. As a reminder, to ask a question, you'll need to press star one, one. One moment for our next question. Our next question comes from the line of Jeffrey Hung with Morgan Stanley. Your line is now open. Thanks for taking my questions. I guess, why do you think that the sparing of lean muscle was more pronounced in pediatrics? And then the second question is, this morning, another company with an approved MC4R agonist announced it was beginning a combination study, with GLP-1 in patients early next year. Can you just remind us of your plans for studying setmelanotide with GLP-1, and why would or would not make sense in the patient populations you've been focusing on? Thanks. Yeah. So, the lean and sparing in kids, I think this goes back to the challenge of interpreting DEXA scans in adolescents and children, because they got other, you know, the hormonal changes which are impacting their, you know, whether they're gaining more lean body mass or more fat mass. Again, different between boys and girls, obviously. So, that's it. I think. We had a very small number of adults, so I just, I can't conclude. I mean, the one adult you'll see on the page, who's in our 12, who came down from a 50 and is now down to a BMI of 37. I mean, he continues to, his BMI continues to come down, and it's just been a very steady, slow, gradual decrease, you know, for him. I don't know what a longer-term DEXA scan would look like for that individual, but again, I'm going to plead the data is just too small to make further assumptions there. And then your question was around a combo therapy. And, you know, combo therapies, again, you know, obesity is complex. Like many complex medical conditions, more than one drugs often get used. People gain weight for more than one reason, and that for sure is going to happen in this world. We have doctors who are, you know, already playing around with that. There's some very good results anecdotally. So it's gonna happen in a way that makes sense. I think what we're encouraged by and where I think this is gonna go, if you have a deficit in this pathway, and like I said, you're missing the hormone, that's where you start. That's the foundational element of this, and you replace that, and then if you need something else on top of that to address some other aspect of your presentation, back to, you know, some other pathway driven, you know, addicted to X, Y, or Z, you know, another treatment, the GLP itself may be incredibly helpful and effective in addressing that part of your equation. So the combo would work and would work better that way. We don't have immediate plans for studying in combination. We'll let some of this play out in the real world here. I think our focus right now is really helping people understand the foundational element of replacing this hormone, and we'll work at that for a while and then see where we go. Great. Thank you. Thanks, Tim. Thank you. One moment for our next question, please. Our next question comes from the line of Whitney Ijem with Canaccord Genuity. Your line is now open. Hey, guys. Congrats on the data from me as well. One quick, I guess, follow-up clarification question on the lifestyle modifications. I understand that no guidance was given in the phase II. Can you remind us that I believe that's also the case in phase III, but I wanted to double-check. And then second part of that is, while no guidance is being given, is that being tracked or kind of controlled for, I guess, in any way, if patients all of a sudden decide they want to do that themselves? So there is no guidance for the phase III, so we, we've stayed with exactly the same overall trial structure. And what you know, what we hear is, patients, it's highly heterogeneous in terms of, you know, how, you know, controlled, somebody's environment is and how, how adherent they are. I think, again, what's encouraging about this data is it's, it just trumps, you know, whatever your background state is, you know, this will take you to a different place, is what you know, this data would suggest. So, I'm not, you know, it's not surprising. This is incredibly encouraging and supportive of the fact that, you know, we had a good response at 16 weeks. It wasn't a transient effect, that this is looks like it's a durable effect, and so our one-year trial should hopefully reconfirm that. And there'll be a range of lifestyle practices that people will follow within that, but it shouldn't impact the overall result. Very helpful. Thank you. Thank you. I'm currently showing no further questions at this time. I'd like to hand the conference back over to Mr. David Meeker for closing remarks. Yeah. Well, thanks all for joining this morning. Again, obviously, you know, exciting moment for Rhythm as we continue to learn more about the effect of setmelanotide in HO, and we very much look forward to further updates, one of which will be coming in the not too distant future with our Q3 earnings call. So talk to you soon. Bye. That concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a wonderful day.