Hello and welcome to Wave Life Sciences' positive interim clinical data from the INLIGHT trial of WVE-007 and obesity call. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question-and-answer session. Also, as a reminder, this conference is being recorded today. I will now turn the call over to Kate Rausch, Vice President, Investor Relations and Corporate Affairs. Thank you, Operator. This morning, we issued a press release announcing positive interim clinical data from our ongoing phase I INLIGHT trial of WVE-007 in individuals living with overweight or obesity. Our press release can be found in the Investor Relations section of our website, www.wavelifesciences.com. The slide presentation to accompany this call will be available on the website following the prepared remarks. Before we begin, I would like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2024. We undertake no obligation to update or revise any forward-looking statement for any reason. Today, Dr. Paul Bolno, President and Chief Executive Officer, will begin with opening remarks. Next, Dr. Erik Ingels son, Chief Scientific Officer, will highlight WVE-007, our INHBE GalNAc- siRNA, and Dr. Chris Wright, Chief Medical Officer, will present the interim INLIGHT clinical data. Last, Paul will conclude with next steps and anticipated milestones before turning it to Q&A. Dr. Chandra Vargeese, Chief Technology Officer, will also be available to answer questions. I'd now like to turn the call over to Paul. Thank you, Kate. At Wave, our goal is to translate powerful human genetic insights into transformational medicines and with WVE-007, we are addressing a significant unmet need in individuals living with obesity. In particular, our focus has been on meaningfully improving body composition by reducing fat, in particular harmful visceral fat, and preserving muscle and as you'll see, that's exactly what we did. Today, we're excited to share a significant milestone towards this goal with the first clinical translation of 007 in our phase I INLIGHT study, which has exceeded our expectations. We've long stated that our goal with the three-month data from our 240-mg cohort was to demonstrate that we are on the curve to deliver meaningful fat loss and with today's update, after only three months, we're excited to be observing fat loss similar to GLP-1s without their associated impact on muscle. What was particularly remarkable was that this was despite INLIGHT investigating healthier participants without diet or exercise modifications. Just three months after a single dose, 007 led to dramatic improvements in body composition, with substantial reductions in fat, including a 4.5% reduction in total body fat and a 9.4% reduction in visceral fat. Importantly, we observed clear evidence of muscle preservation with a 3.2% increase in lean mass. Our best-in-class SpiNA design is leading to robust and durable suppression of Activin E, supporting once or twice per year dosing, and we're seeing remarkably clean safety profile through our fourth 600-mg cohort. As you'll hear today, these results support a potentially transformative profile and drive our excitement in advancing INLIGHT and further development of 007 across multiple settings. Now, to provide further background on 007's differentiated approach and strong biological foundation, I'd like to turn the call over to Erik. Thank you, Paul. Before diving further into today's results, it's important to reflect on the current obesity treatment landscape and why we believe WVE-007 is positioned to deliver a truly transformative, novel therapeutic approach. Individuals living with obesity face markedly higher risks of a range of serious conditions, including cardiovascular disease, type 2 diabetes, and several cancers. The key driver of this elevated disease risk is unhealthy body composition, with an excess of body fat in relation to lean mass. While GLP-1 receptor agonists and other incretins have transformed obesity care, their impact is often limited by a substantial loss of muscle mass, as well as tolerability challenges, especially GI side effects, frequent dosing, and high discontinuation rates. The loss of muscle with incretins is particularly important to emphasize in this context due to the important role of muscle in metabolism and weight maintenance. We believe that an improved body composition is the key goal of any effective obesity treatment strategy. Body fat, in particular excess visceral fat, including fat around internal organs, is strongly linked to diseases like type 2 diabetes, fatty liver, and cardiovascular disease, acting through chronic inflammation and insulin resistance. Additionally, skeletal muscle, which is the main component of lean mass, is important for improved insulin sensitivity, for sustaining a higher basal metabolic rate, which is critical for long-term weight maintenance, as well as for preservation of muscle strength and function, and to reduce the risk of sarcopenia and frailty. There's a lot of literature from over the last few decades demonstrating the strong links of increased visceral fat with insulin resistance, MASH, type 2 diabetes, and cardiovascular disease. As shown on the left, decreases of 5%-10% visceral fat lead to substantial and clinically meaningful improvements across a number of cardiometabolic disorders. As shown on the right, you can see that increasing levels of visceral fat are associated with a dramatically increased number of cardiovascular events. For these reasons, we're excited about the approach we're taking with 007 that leverages a completely orthogonal mechanism from gut-brain signaling and appetite suppression by inducing fat loss through lipolysis, breakdown of triglycerides, directly in adipocytes. 007 aims to improve body composition by reducing body fat, in particular visceral fat, while preserving muscle to deliver a healthier cardiometabolic profile. WVE-007 targets Inhibin E, or inhibin subunit beta E, with a strong foundation in gene genetics, which has been shown to increase the probability of successful drug development by up to two- to fourfold, with coding variant evidence in the upper part of that range. In the UK Biobank and other cohorts, heterozygous Inhibin E loss-of-function variant carriers exhibited a healthier metabolic profile with lower abdominal obesity by waist-to-hip ratio and lower visceral adipose volume, lower triglycerides, ApoB, and fasting glucose, and higher HDL cholesterol. We also have favorable associations with liver traits, such as ALT and cT1, a measure of liver inflammation and fibrosis, and lower risk of type 2 diabetes and coronary heart disease. Our therapeutic hypothesis is straightforward. By silencing Inhibin E mRNA, we aim to recapitulate the protective phenotypes seen in these heterozygous loss-of-function variant carriers. Inhibin E is produced in the liver, where two of the subunits dimerize to form the hepatokine Activin E. Activin E gets released into circulation, where it binds in a specific manner to ALK7 receptors on adipocytes. The resulting signaling blocks adipose lipolysis, promoting abdominal adiposity and increasing risk for cardiovascular disease and type 2 diabetes. By reducing hepatic Inhibin E mRNA with a GalNAc siRNA, we lower circulating Activin E, decrease ALK7 signaling in adipose tissue, and release the brake on lipolysis, which is expected to shrink adipocytes and reduce abdominal adiposity, thereby lowering cardiometabolic risk. In addition to Inhibin E's strong foundation in human genetics, we believe 007 is differentiated by our proprietary chemistry, which makes us well-positioned to deliver a potentially best-in-class approach. 007 is a GalNAc siRNA using Wave's SpiNA design, including backbone stereochemistry and PN chemistry, to enhance interactions with Ago2 and to improve silencing potency and durability. We have demonstrated the dramatic improvement of Ago2 loading, which is a critical differentiator when trying to silence Inhibin E, a target that is hard to keep sufficiently and durably suppressed, presumably due to evolutionary pressure for the need to store energy efficiently. Based on observations from genetic studies, we would expect that Inhibin E silencing and Activin E reductions should lead to meaningful improvements in body composition as well as cardiometabolic health, which should be the main objectives of any obesity medication. As we have shared in a number of previous presentations, our preclinical studies show that by reducing Inhibin E mRNA and circulating Activin E levels, increased adipocyte lipolysis leads to reduction of adipocyte sizes and fat loss, in particular visceral fat. This, in turn, results in a shift from pro-inflammatory to anti-inflammatory macrophages and less fibrosis in visceral adipose tissue, as well as improved insulin sensitivity, changes that can contribute to a lower risk of cardiovascular disease and type 2 diabetes. As we also shared previously, our preclinical data in diet-induced obesity mice strongly supports 007's ability to both potently and durably knock down Inhibin E and reduce circulating Activin E, leading to substantial changes to body composition with fat loss, in particular visceral fat, while sparing muscle. Based on our preclinical data, we would expect reductions of Activin E levels of at least 70% to translate to improvements of body composition in clinical setting. As observed in the right figure, when comparing the kinetics, weight loss with Inhibin E siRNA was similar in magnitude to semaglutide, but occurred more gradually. A potential explanation for the initially slower weight loss could be that the preservation of lean mass is offsetting weight loss early on, but that over time, the substantial fat loss is translating to weight loss as lean mass stabilizes. As Chris will share in further detail momentarily, our results with 007 represent the first clinical data linking durable Inhibin E silencing to meaningful changes in body composition in humans. With the clinical translation of 007's strong human genetics foundation and our robust preclinical data, we're incredibly excited to continue to evaluate 007 across cohorts and with longer follow-up in INLIGHT, where we expect to continue to see the loss of total and visceral fat with muscle preservation. With that, I'll now turn it over to Chris to walk through the INLIGHT clinical data in more detail. Thanks, Erik. Good morning to everybody on the call. As a reminder, INLIGHT is a placebo-controlled single ascending dose study, randomized three to one active to placebo, with potential to escalate up to five single dose cohorts and plans for additional multiple dose cohorts. It's designed as a safety, tolerability, PK study. Participants are healthy individuals living with overweight and mild obesity, with key inclusion criteria of HbA1c less than 5.9 and BMI between 28 and 35. The study does not require diet or exercise modifications or counseling. In addition to safety, tolerability, PK, and activin E levels, the study has exploratory endpoints of body composition by DEXA, biomarkers, and body weight. INLIGHT is currently ongoing at multiple clinical trial sites, including in the U.S. We began testing WVE-007 at our lowest subtherapeutic dose of 75 mg in eight participants, which did not include DEXA and was primarily to affirm early safety in PK-PD. We next evaluated the 240-mg, 400-mg, and 600-mg ascending dose cohort, which are expected to be at or above our therapeutic threshold. We have expanded to and fully dosed 32 subjects in each of these cohorts based on the favorable safety profile. Today's update primarily covers three-month follow-up data from our first potentially therapeutic 240-mg cohort, N equals 32. In addition, further updates on safety for the 75 mg through 600-mg cohorts and PK from 75 mg to 400 mg cohorts are provided. Baseline characteristics were generally well-balanced across the treatment arms. Participants were in their late 30s to early 40s on average, with a mix of men and women in each cohort, with a somewhat higher proportion of females in the 75-mg group and males in the 240-mg group compared to placebo. Mean baseline BMI was approximately 32 kilograms per square meter in the treatment cohorts, consistent with the participants having healthy overweight or mild obesity. In our cohorts from doses of 75 mgs to 600 mgs, including placebo, there were no discontinuations, serious TEAEs, or deaths. All study drug-related AEs were mild. There were no clinically meaningful changes in lipids, glucose, or other clinical laboratory measurements, including liver function tests through 600 mgs. Overall, we are very pleased with the favorable safety profile that WVE-007 continues to exhibit across a wide range of doses in our first-in-human trial to date. Following our update at research day, we continue to see robust and durable reductions of Activin E. In this chart, we show the dose-dependent Activin E decreases over time across three single dose levels of WVE-007 and placebo. The percentage reduction of Activin E from baseline is shown on the Y-axis, with days on the study on the X-axis. As a reminder, at research day, we reported that at day 29, we saw statistically significant mean Activin E reductions of 56% at 75 mgs, 75% at 240 mgs, and 85% at 400 mgs. Activin E reductions in the 75-mg cohort were sustained out to six months and reached a maximum reduction of 59%. Both the 240-mg and 400-mg dose levels still appear to be trending downward at day 29. We are now pleased to show that these statistically significant reductions are enhanced and persist in the 240-mg cohort at later time points, with up to a 78% mean reduction in Activin E at day 43 and sustained decreases of greater than 75% out to day 85, which is approximately three months. These data continue to support a highly convenient dosing interval of once or twice a year. So what do these durable and robust reductions in Activin E translate into? As I will now cover, we are seeing significant fat loss and meaningful improvements in body composition. Even at our initial three-month time point, in our lowest therapeutic 240-mg single dose cohort, if you look from left to right, we observed significant reductions from baseline in visceral fat of 9.4%, total fat mass loss of 4.5%, with increases in lean mass of 3.2% from baseline as measured by DEXA. Importantly, these changes were observed in otherwise healthy individuals with mild obesity and without any protocol-mandated diet or exercise modifications. No significant changes from baseline were observed on any DEXA measure in the placebo arm. Overall, these data demonstrate that a single dose of WVE-007 can shift body composition towards less visceral and total fat while preserving muscle, consistent with our preclinical findings and with the underlying human genetics. With this important and unique clinical proof of principle, we are looking forward to evaluating the impact of this mechanism with higher doses and over longer durations throughout 2026. To help contextualize these body composition changes at the three-month time point, we evaluated our results and examined those of the BELIEVE phase II study, evaluating semaglutide and the myostatin inhibitor, bimagrumab, where DEXA scans were available at the 12-week time point. On the left are the placebo-adjusted changes from our INLIGHT study with a single 240-mg dose of WVE-007 at three months in participants with a mean BMI of around 32. A 9.2% treatment effect was observed on visceral fat, as well as a 4% decrease in total fat mass. There were also small improvements in lean mass and decreases in total mass of 0.9%. In the center and on the right are the estimated placebo-adjusted changes from the BELIEVE phase II trial, which investigated weekly semaglutide and intravenous bimagrumab in participants with BMIs around 36.5. The total placebo-adjusted fat mass reductions for semaglutide were of a similar magnitude as for 007 at 4.2%, but there was substantial lean mass reduction of 3.5% or approximately 4.5 pounds. Visceral fat reduction was 5.7%, and total mass reduction was 3.8%. Notably, 007 showed a placebo-adjusted reduction in total fat mass on par with semaglutide at 12 weeks, while simultaneously preserving lean mass and driving greater reductions of visceral fat. When evaluating bimagrumab, which increases lean mass with reported safety limitations, there are modest reductions in visceral and total fat mass, along with increases in lean mass leading to small increases in total mass. It is particularly encouraging to see 007 driving total fat reductions on par with semaglutide or greater at the three-month time point, even in a lower BMI, healthier population without diet or exercise modifications. Coupled with the convenience of once or twice yearly dosing, lean mass preservation, and a favorable safety profile, we believe 007 has the potential to transform the obesity treatment paradigm, and we look forward to keeping you updated on our progress in INLIGHT. I'll now turn the call back to Paul. Thanks, Chris. WVE-007 has demonstrated a potentially transformative therapeutic profile by improving body composition, specifically a loss of fat, including harmful visceral fat, with muscle preservation. All of this is delivered with a single subcutaneous injection given only once or twice a year and a favorable safety and tolerability profile. Taken together, 007 has the potential to address the significant unmet needs that remain in obesity. The clinical translation of WVE-007 in INLIGHT fortifies our excitement in other treatment settings where we've demonstrated compelling preclinical evidence. As shown on the left, in mice, we've observed approximately twofold greater weight loss as an add-on to semaglutide versus semaglutide alone. And on the right, the ability of WVE-007 to curtail rebound weight gain following cessation of semaglutide, providing powerful data for its utility in a maintenance setting. This translation now unlocks opportunities to investigate 007 in multiple treatment settings. While INLIGHT is currently investigating otherwise healthy participants with a markedly lower BMI compared to other obesity trials and no diet or exercise modifications, we believe 007's favorable safety profile and ability to drive reductions in fat while preserving muscle also support investigating 007 as a monotherapy in higher BMI populations with cardiometabolic comorbidities. With its orthogonal mechanism, we also see an opportunity to use 007 as an add-on to incretins. And within the community, there is particular excitement about 007's potential as a maintenance therapy, which would allow people to transition off incretin therapies while at the same time preventing rebound weight gain, preserving muscle, and sustaining cardiometabolic health. Planning for these phase II trials in these settings is now underway. The substantial reductions in fat mass we've observed at this three-month time point are already on par with semaglutide. As we look ahead to the coming quarters, we have multiple opportunities to assess the impact of duration and dose on the continued improvement in body composition. Next quarter, we'll have six months of follow-up data from the 240-mg cohort, as well as three months of follow-up data from the 400-mg cohort. In the second quarter of 2026, we'll have six-month follow-up data from the 400-mg cohort, as well as three-month data from the 600-mg cohort. Before turning the call over to questions, I would like to take a moment to thank all the individuals participating in our INLIGHT clinical trial, the clinicians involved, and the study site staff. They inspire the work we do every day, and from everyone at Wave, we'd like to express our sincerest gratitude. With that, I'll turn the call over to the operator for Q&A. We will now move into our Q&A session. For those of you who are joining us via Zoom, if you would like to ask a question at this time, please raise your hand by clicking the raise hand at the bottom of your Zoom window. Once called upon, please unmute your audio to ask your question. Our first question comes from Joon Lee at Truist Securities. Please unmute your line and ask your question. Great. Congrats on the great data, and thanks for taking our questions. Looks like there was a net weight gain in the placebo arm driven by increase in lean mass. How do you explain that, given most weight loss trials, the placebo arm loses weight, not gain? And bigger picture down the road, how are you looking at the potential labeling differentiation to compete against GLP-1s, which are now just $300-$600 per month? Thank you. Yeah, no, thank you, Joon. And as you see, there was a gain in the placebo arm as well as in the treatment arm from baseline. Remember that this did not require diet and exercise, and yet we still saw a statistically significant increase in lean mass. But if you look at the placebo-adjusted data sets, it was about a 0.9% increase. And we also saw, as you pointed out, a 0.9% decrease in total mass. So I think ultimately, we have a medicine that's driving weight loss down by losing fat. And this is very consistent with our preclinical data that demonstrated strong fat reduction and, over time, muscle stabilization, both of which led to total body weight decrease compared to semaglutide. So again, I think it's really a powerful medicine in a world that's really looking for improvements in body composition long-term. To your point on the evolution of the commercial landscape with the pricing pressures on GLP-1s, there are over a billion patients worldwide living with obesity. And I think the power of what we've shown today is that with a once to twice-a-year subcutaneous administration, the one that can open up monotherapy to maintenance, I think it creates a powerful disruptor to the marketplace. So we're excited to accelerate it and to generate those data. And I think, you know, lastly, you know, I think it's very much tied to the direction that the FDA is moving to obesity therapies. You know, while they say in guidance that there's a 5% weight loss requirement for approval, it is very clear from the FDA that they want to see weight loss driven from fat loss and not from muscle explicitly. I think this product definitely delivers within the realm of what the agency is looking for. Joon, if I also can add, you asked about other trials. Remember that, you know, placebo loses weight is mostly from the phase II and III trials where individuals are under intense lifestyle intervention. In this case, we didn't give any diet or exercise modifications. So it's hard to compare in that case. Great. And, you know, just to follow up, is weight loss going to be the regulatory hurdle that you guys are going to hoop, I mean, jump over, or are you looking at something else as an approval endpoint down the road? Thank you. Yeah, we're not focused on creating new endpoints. I think the goal is that weight loss remains an approval endpoint, and it remains a focus of what we see with inhibiting human genetics in our mouse models and ultimately what we believe will continue to occur in humans. So very much the focus. But again, I think we're seeing momentum across the clinical community, the patient community, and the regulatory community to drive a focus on body composition and driving that weight loss and preserving lean mass and losing fat. I mean, as Chris mentioned on the call, we're sounding at the first three-month time point that actually a lot of that predominant weight loss driven off of the GLP-1s is fat. It was almost 4.5 pounds of fat that were lost at that early point in kinetics. Sorry, muscle. Muscle. And so by preserving that muscle, that's a lot of muscle to lose very early. And so we do see it as critical to lose fat, which is what we saw. Very impressive. Thank you so much and congrats again. Yeah, thank you. Our next question comes from Steve Seedhouse at Cantor Fitzgerald. Please unmute your line and ask your question. Great. Good morning. Thank you. I wanted to first ask if you could comment on the precision and accuracy of the DEXA methodology that you're using in this study. I think it has a pretty good reputation, but just wanted to confirm how much variance across patients in the study you'd expect to be just biological versus actually technical margin of error from the measurement. And I have a couple of follow-ups. From the DEXA perspective, we used a standard methodology and had a group that made sure that it was standardized across all the sites and all the data was analyzed in detail to ensure quality across the board. Just relatedly, what was the, if you have it handy, what was the highest percent fat loss and highest percent total weight loss that you saw in any individual patient in the treatment arm? Do you have that? Yeah. I mean, obviously, it was tight. This is the data that we're sharing in the meantime. We'll have more data coming in meetings in the future. But I think what's really important and what drives weight loss, and this is something that if you looked at the Activin E data early on between the 75 and as we got to the 240, is how tight the knockdown got. So if you look at the error bars on Activin E at the 75-mg cohort, there was a lot more variation. And as you moved into higher doses, the expression and knockdown got tighter and tighter, and that translated to good, tight fat loss and muscle preservation. Got it. Just trying to get it basically, as you follow through six months, your level of conviction that the true effect of the drug here with increasing fat loss over time that would be expected would sort of easily reveal itself. And then the other question I wanted to ask is, bimagrumab has an adverse event profile that includes diarrhea, muscle spasms, I think acne as well. Are you seeing any imbalance in those features specifically from 007? I'll answer the last one first, simply. No. As you saw, it's a remarkably clean safety and tolerability profile, and so that obviously has us. It's an important feature, one, to your point around thinking about some of the evolving muscle sparing therapies, but importantly, as we think about other weight loss medicines, and again, bodes well for a drug that is focused on body composition, fat loss, and muscle sparing. Yeah. I mean, as we noted, we didn't really see any clinically meaningful changes in lipids or LFTs or glucose or any other clinical laboratory measure. Okay, and just real quick, lastly, do you have data on any patients yet through six months in the 240-mg cohort, or is that sort of batched and received all together at some point in the first quarter? Yeah, it's batched and received together. But getting back to an early point we made of how do we expect to see, and I think your forward-looking piece and trying to see variability, we have an extraordinary amount of confidence in what happens as we continue to run this study forward. That's driven on both the fact of sustained durable knockdown of the Activin E expression and really the strong translation that we can continue to see in the preclinical models that is, so long as you're suppressing Activin E, fat loss continues. So again, the data that we continue to expect as a function of the duration of time, so long as Activin E is suppressed, is we do expect to see continued fat loss. Terrific. Exciting update. Thanks so much. Thank you. As a reminder, please limit your questions to one question and one follow-up. Our next question comes from Samantha Semenkow at Citi. Please unmute your line and ask your question. Hi, this is Ben on for Sam. Thanks so much for taking the questions. To start, can you talk about the slope of fat loss and the increase in lean mass? Are you seeing any plateauing in the lean mass? And then from a genetic perspective, what is driving the increase in lean mass? Yeah. I mean, I think we continue to see the slope of fat loss. And lean mass, it's interesting in preclinical data, it goes up and stabilizes. So if that continues to translate, we continue to expect to see, and that's been seen in other muscle medicines. So we expect to see sustained support in lean mass with continued suppression again. And that's really the biology and the genetics. So long as Inhibin E and Activin E is suppressed, you'll continue to see fat reductions. And we see that slope in kinetics in our preclinical experience compared to semaglutide. And we now see it in humans. And again, I think it's astounding when we go back to the comparator in mice and we go back to our comparator data looking at cross studies in humans, that impact on GLP-1s on muscle is profound, right? 4.5-pound decline at the beginning versus ours, which is purely fat. And so again, we expect those characteristics to continue. And to add to Paul's point there, that's the expectation based on our preclinical. But just to be clear, from the clinical, we only have a DEXA from baseline zero, and then now at three months, we only have these two. So it's not really kind of a trajectory yet, which is two time points with the slope. Then as a quick follow-up, maybe based on your preclinical models, have you observed any kind of ceiling effects in either the fat loss or the muscle preservation, just sort of thinking ahead through to the 400- and 600-mg cohorts? Yeah, muscles stay stabilized. That's really a function of the fact that you're not shifting. I think we're all used to a number of increases. You're not shifting to a starvation phenotype where you break down muscle to provide energy and you break down fat. What's unique again about Inhibin E is it's purely a fat loss component. And actually, if you follow the mouse data out, which is pretty interesting, is the total body weight kind of crosses the semaglutide arm, which means that it actually shows that actually as long as you have fat to deplete, you're able to continue to decrease your fat content. And that's another reason why when we think about this study where we have a particularly low BMI in comparison to the historical when all of you were looking at obesity studies, if you look at BELIEVE, it was nearly a 30s. BMIs were nearly 37. So if we think about having larger fat subcutaneously in visceral, the magnitude of effect should actually be potentially larger like it was in the animal model. So again, bodes well for future subsequent studies in an obese population with a higher BMI and comorbidities. Great. Thank you so much. Thank you. Our next question comes from Salim Syed at Mizuho Securities. Please unmute your line and ask your question. All right. Can you hear me now? We can hear you. Yes. Okay. Great. Paul, congrats on the data. I know you mentioned that the data here is pretty tight on the bars. Could you give us just some quantification to how tight it was, just given we don't have any sort of spider plot data here just on maybe some of the measurements, the 9.2% and the 4% that you provided? How tight exactly is this data? Yeah. I mean, we can share the data that we shared today. All the subsequent data would be at future presentations. But I think the key is that we're getting strong exposure, strong consistent knockdown of Activin E, and it's translating across to statistically significant changes from baseline in fat and increasingly muscle. And so again, when we talked to a number of you going into this several months ago, I think our thought was we would be fortunate in a phase I study without diet or exercise, with all normals, with a low BMI, that it would be really nice to start seeing trends on this. And so the fact that we're actually delivering statistically significant reductions in both fat and on lean mass, I think, speaks to the power of the data. Okay. And then just to follow up, the data that's coming in the 1Q, could you maybe just preview that for us? What are your expectations for the six-month data and for the next cohort three-month data, please? Thank you. Yeah. I think what's clear, and we've said this a number of times, that the goal is, are we on that curve of fat loss? And I think with today's data, we deliver that we are on the curve of fat loss with GLP-1s, with muscle preservation. And we expect continued based on our preclinical experience that so long again as we have sustained Activin E suppression, that we would expect those findings to continue. So muscle preservation continuing and fat loss continuing. And so I think it, again, bodes very, very well for our Q1 data updates over longer duration, so where we expect to see that impact continue. And we're also going to learn about dose impact. Does that accelerate the curve? Does that help us push the dosing frequency out with less? Again, I think the power is going to be in both looking at both the dose as well as, most importantly, duration. We'll have multiple data sets as we move through not just the first quarter, but beyond on really elucidating the power of Inhibin E. Okay. Thank you. Congrats again. Thank you. Our next question comes from Ben Burnett at Wells Fargo. Please unmute your line and ask your question. Okay. Great. Can you guys hear me? Yes. Okay. Excellent. I just want to ask about, so you mentioned that there was no diet or exercise modifications. How was that implemented in the study? Excellent. Sure. Yeah, so this is a typical first-in-human study. So in that context, you don't generally limit diet and exercise in the way that you would for a phase II weight loss study, so that was just part of a standard approach to first-in-human studies when you're looking at safety and tolerability. We anticipate for our phase II studies, we would, in fact, include similar criteria as others have as well. Okay. Most interesting way to look at this is a real-world study. I mean, I think it's always been something that we've become enamored in looking at the genetics of Inhibin E that this is a population that's walking around that has a protective loss of function that drives reductions in abdominal visceral fat that has better cardiovascular outcomes, as Erik said, and better type 2 diabetes outcomes, and as part of living their normal lives and so in a lot of ways, the phase I portion of the study gives us kind of a real-world environment with which to assess that indeed that's true. I mean, even in mice, what was fascinating on the prevention of rebound weight gain is when we stopped the GLP-1 and predosed with Inhibin E, despite an increase, so hedonic eating with an increase in caloric consumption, those mice didn't regain weight. And I think it's just really important as we reframe kind of thinking about obesity therapeutics and kind of a completely different paradigm shift. It's not about caloric restriction and essentially starvation. This is about resetting the metabolism to driving fat loss, which allows you to preserve muscle. So it's really exciting, I think, as we think about obesity therapeutics going forward. Okay. That's great. And can I also ask? I mean, so the hypothesis is sort of playing out that you're seeing muscle sparing. And I think a lot of us are kind of looking at the GLP-1s and what else is sort of coming down kind of the obesity pipeline as sort of comps for what to expect. I guess if you are indeed sure that you could spare muscle, I'd love to hear what ultimate level of fat loss do you want to see for this to be commercially competitive? I think we want to continue to see where we are. I mean, I think we're starting at this point, and we'll continue to follow a downward trend, and we're on par with GLP-1s as it states at this very, very early time point. So I think it bodes really well that we're competitive with GLP-1s on fat loss. We see that in our preclinical models as well, but not to underestimate the power of sparing muscle. I mean, muscle is an endocrine organ as well in terms of insulin sensitivity and outcomes, and also drives energy consumption, which actually ultimately continues to drive better body composition, so I think in profile, we're on that path already as it stands. But I think stepping back and thinking about, to your point, just the evolving landscape, I do think this idea of how do you put patients on medicines where at that very early time point, the majority lose a massive amount of muscle at those early time points? You retain it, you lose fat. And that's all kind of thinking about monotherapy settings. I think one of the very interesting applications is this maintenance concept of ultimately, if we think longitudinally about how to keep patients with a better body composition, having a once to twice-a-year shot where you continue to drive fat loss and preserve muscle, we think is a highly competitive profile. Great. Thank you so much. And congrats on the data. Thank you. Our next question comes from Yun Zhong at Wedbush Securities. Please unmute your line and ask your question. Hi. Good morning. Thank you very much for taking the questions and congratulations on the very positive data. So the first question on the lipid profile, I believe the press release said there were no meaningful changes in lipid profile, but I thought heterozygous carriers, they do have a better lipid profile. So do you expect the treatment to maybe lead to any metabolic benefit as GLP-1 does to reduce the risk of other comorbidities? Yeah. Based on the human genetics, we would indeed expect that lipid levels, glucose, and other metabolic parameters would improve. Now, remember that these are otherwise healthy overweight and obese individuals. So you wouldn't really expect a lot of effect in this patient segment. That's also one of the reasons why we're very excited about the phase II trials in higher BMI individuals with some of those high triglycerides or prediabetics, where we definitely would expect this to be beneficial with decreasing levels. I see. And then the second question, given the lean mass increase in both treatment cohort and the placebo cohort, I understand that there were no modifications in diet, but are you collecting data on any potential impact on diet or calorie intake or maybe even exercise pattern? No. So there's no requirement in this study. I mean, hence, people are going about their normal activities, so you're not incentivizing them that this is a weight loss study to participate in those activities. Okay. Great. Thank you very much. Thank you. Our next question comes from Cheng Li with Oppenheimer. Please unmute your line and ask your question. Oh, hi. Congrats on the super impressive data, and thanks for taking the question. Just a couple from us. So first, can you maybe comment on, I mean, recognizing the small patient number, but curious if you can comment on any baseline characteristic can predict the weight loss? For example, you see maybe greater weight loss in female versus male or maybe higher BMI versus lower BMI. Also wondering if baseline Activin E level can predict response to WVE-0 07? Yeah. I mean, first, I think your question was interesting because if you set that up compared to all of the other comparator obesity studies that we were referring to on this call, and people will, I'm sure, do others, is actually in every one of those settings, this study was essentially handicapped in the sense that the BMIs were lower, so to your point, we're starting with a lower BMI and seeing these data that are comparable with the three-week data on GLP-1s, and actually, as Chris pointed out, we actually had in this arm more males than females, so if we look at kind of all of the, as you point out on the obesity studies, things that would drive that to a different outcome, this medicine performed extraordinarily well in those settings. But stepping back, it is, as to your point, a small study to be able to discern these features. But again, bodes really well. I mean, I think while that separates, I think thinking about safety, convenience, and opportunity, I mean, the profile is distinguishable again on all parameters. Okay. Got it. And also, I think you are measuring some blood biomarkers. So any comments on those biomarkers relevant to anti-inflammation or anti-fibrosis you can share? Yeah. I mean, as part of the study, I mean, obviously, as we shared on what would be the first biomarker we look at, we hope DEXA was going to be a good biomarker to look at body composition changes, and indeed it was. We are also collecting over the course of the study different panels. But obviously, to your point on Activin E, getting more samples. I mean, we'll have over 100 patients' worth of data as the study continues to progress. All patients are dosed in the study through 600 mgs. So the study is now running. And as we accumulate that data, both on Activin E levels and biomarker, we'll be able to assess that both on duration. So we want to look at dynamics of those biomarkers over time as well as at higher doses. So we want to explore both the dose responsiveness as well as duration of those biomarkers. Okay. Thank you and congrats again on the data. Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Please unmute your line and ask your question. Great. Thanks so much. Congratulations on this really groundbreaking data. I guess I have a question on efficacy and also safety. So first of all, how would you expect the weight loss effects to differ in patients who are obese and are entitled to diet and exercise in a study like we might see in the next phase? And just conceptually, why at a fundamental basis would you expect the results to differ based on the mechanism? And then on safety, it's really encouraging you saw no discontinuations at three months. I think we do see some with the GLPs due to GI issues. So can you just dissect that for us a little bit? Thanks. Yeah. I mean, just to take the first one. I mean, what's interesting is we think about increased BMIs. To your point, as you get larger and patients with more subcutaneous fat as well as visceral fat, you have more opportunity to see substantial reductions. So I think we see that preclinically, the reductions are dramatic. I think we'll have the opportunity in patients with larger BMIs to see both big impacts on both visceral fat as well as subcutaneous fat as we actually move into those larger BMI patients, as the last question was alluding to. I think there's a great opportunity, again, in a forward-looking way, that we de-risk the Inhibin E mechanism in the challenging population of a phase I healthy overweight patient population with low BMI. I mean, I think this is, again, exceeded our expectations to see this early. I think fat loss is happening extraordinarily quickly. And again, mirrors well to what we've seen in human genetics as well as in the diet-induced obesity mouse models. So that's exciting. As far as safety, I'll let Chris answer that question. Sure. So to your question around discontinuation, so we haven't really seen discontinuations as we show in the safety table. Just to comment on the overall duration. So it's not just three months. So the lower dose, 75 mg, is out to six months. And we saw no discontinuations there. And then for 240, we're also beyond the three-month timeframe at this point. The data was at three months, but those patients continue on, and there's been no discontinuations to date. And then from the GI perspective. Sorry, go ahead. No, you're going to what I was going to ask. Thanks. Okay. Yeah. I wasn't finished. I think I was getting to your second question. And as we also showed, there were no, all the treatment-related adverse events were mild, and there were no GI issues. Perfect. Thanks again. Thank you. You're welcome. Our next question comes from Cha Cha Yang at Jefferies. Please unmute your line and ask your question. Hi. This is Cha Cha on for Roger Song. Thanks for taking our question, and congrats on the really great data. I was just hoping that you can speak to your decision to use bimagrumab as a benchmark, especially as Lilly has halted that development of the product. And then also, if you could give some more color on timelines for potentially a maintenance trial and your thoughts on potentially starting that trial before INLIGHT wraps. Yeah. I'll take the first question first. It wasn't intentionally to go benchmark against bimagrumab in order to find the study where we could look at three-month DEXA data for semaglutide. That's in the BELIEVE 2 study, which was a combination study looking at what happened when you combined the bimagrumab with semaglutide. So in order to look at that data, obviously, the bimagrumab was a component of that study, and we needed to share the full data at that time point across the bimagrumab and sema. I think it's incredibly encouraging to your point that, one, we delivered fat loss similar to GLP-1s in that setting. But when we also looked at, to your point, bimagrumab, where we're seeing now preservation of lean mass with an incredible safety profile, right, and a convenience factor of a once to twice-a-year administration, I think when we look across both those settings, it really points to the potential of an INHBE inhibitor to really become a distinguishing opportunity within the obesity space. So yeah, that was the rationale around that. In terms of plans, because there are a number of opportunities to drive it forward, we are driving that. We don't believe 600 is necessary. So we don't have to complete the final stages of the INLIGHT study because those will follow patients out for 12 months, right? So that's the opportunity to continue to look for further weight loss. But the start of the phase II, particularly as we've been talking about a number of times on the call of being able to get this into a setting where we get a bit higher BMI patients to look at impact of effect and comorbidities and to be able to look at both maintenance and add-on, we do fully expect to start those studies. And we'll get further updates in the future when they'll start. Great. Thanks so much. Our next question comes from Catherine Novack at JonesTrading. Please unmute your line and ask your question. Hi. Good morning. Thanks for taking my questions. I just had a question on the prioritization of the different potential phase II studies. It seems like conversations at Obesity Week, for example, a lot of expert opinion was that incremental discontinuation is the ideal setting for Inhibin E. But given what you've seen today, it looks like there could be prioritization in other phase II settings would make sense as well. Just given the resources that you have available and the potential size of some of these studies, where do you think you'd want to focus your efforts in the next year? Yeah. I mean, I think the interesting place, as you pointed out, is obviously seeing the opportunity in the high BMI comorbidity patient and what the opportunity is to change body composition. Again, with a convenient, favorably safe medicine, I think can be disruptive in that monotherapy setting, and really seeing the full opportunity in those higher BMI patients is important. I think the other is the off-ramp study. I mean, as we think about the long-term duration of chronic loss of lean mass in addition to potential for anhedonia, other tolerability issues where a substantial number of patients can't stay on therapy, and then they're worried about regaining that weight back. I think that as you've heard at Obesity Week, and we heard from a number of folks, that setting on the maintenance off-ramp is a very interesting study to do and is really defined. And we've got a number of different potential increments to run that study on to show that we can prevent that, and the data is strong. So we'll continue to do that assessment. That'll drive our prioritization strategy. But I think stepping back, the most important thing is I think we've got a profile that goes strongly into any one of those settings, and we'll be refining our go-to-market strategy around that. Got it. And then given that there are multiple ligands that signal ALK7, is there any thought on compensatory signaling with sustained knockdown of Activin E? What have you and others seen there long-term? So we don't. I mean, I think it's a very interesting question that's coming up as we're seeing more literature on ALK7 and why we remain focused on Inhibin E is that there's a very clean cross-communication between, as Erik pointed out at the very beginning, the liver to adipose signaling. ALK7 is a receptor for some of the other activins. And we've also seen literature now coming out that ALK7 is on some other cell types beyond the adipocyte. And so I think opening up the risk factor for suppressing that where there are other mechanisms that ALK7 signaling is involved in in other cell types. We like the cleanest path, which we said from the very beginning and starting this program, which is you've got a hepatokine that has a very focused receptor and a very important job to do, and we can durably and productively and safely knock that out and in so doing see a robust response. So I think we're very much focused on the inhibiting pathway. Got it. Thank you for taking my questions. Congrats on the data. Thank you. Our next question comes from Madison El-Saadi at B. Riley Securities. Please unmute your line and ask your question. Hey, guys. Congrats on the data. Thanks for taking our question. A broader mechanistic question. We obviously have the animal data, and then we have data from a couple of human readouts. How long do you think patients need to be on drug before that top-line weight loss crosses the GLP-1 weight loss trajectory? And then related to that, it sounds like there are no plans to seek a phase II endpoint on body composition. Thanks. Yeah. I mean, I think the key is, and I think the obesity field will move towards body composition, isn't a negative word on body weight. I think as we had a KOL who runs a massive obesity clinic remind us that the goal of their patients is to help them get leaner. And I think if you imagine what happens when you drive weight loss to a number and lose lean mass and fat, that doesn't create a healthier outcome, but that doesn't equate with not losing weight. And so I think really the focus has to continue to be on substantial reduction in fat, which does reduce body weight and preservation of lean mass. We do see that. I mean, that was the important dataset in the DIO mouse model that tested the bounds. This is not a medicine that plateaued and didn't show weight loss similar to the GLP-1. It was how productive that weight loss was, which is a function of body composition, meaning losing fat, preserving the muscle, and yet the slope of the kinetics was slower, but actually that's a healthier outcome, and so I think if we think about that direction, there's nothing to suggest there's any plateauing effect, and we should continue to see meaningful, durable, safe fat loss. As it relates to the regulatory endpoints, I think all of this is very much aligned with where regulators are trying to move things. I think seeing this kind of pound-for-pound weight loss competition where people are losing real lean mass is being viewed as detrimental, and therefore, there really is a focus on having that weight loss occur on fat, not muscle. I think we're poised to deliver a robust dataset into where we think the regulatory paradigm now is going. Got it, Paul. Thank you. Thank you. Our last question comes from Luca Issi with RBC Capital Markets. Please unmute your line and ask your question. Oh, great. Can you guys hear me okay? Yeah. Hey, Luca. Great. Great. Great. Congrats on the fantastic data. Maybe just a few questions here. Maybe circling back to the prior question, so BD, is this an asset that you're envisioning bringing all the way to the finish line by yourself, or is this a drug that you're maybe planning to partner at some point? Any context there is much appreciated. And then maybe on competition, I think, again, your competitor will have data in early January. So I wonder if you can talk about differentiation versus them. And then maybe lastly on the data, I just want to confirm, is this entire dataset that was presented today coming from a single site in Moldova, or is this a dataset that is coming from a broader number of sites and a broader number of geographies? Thanks so much. Yeah. I'll take your last question first. It's coming from multi-center sites. So we've got sites across Europe, U.K., as well as the U.S. So it's a multi-center site. So I think you're referring to where it started, but it's expanded since then. As it relates to your first question, I think absolutely we intend to continue to drive this program forward. As we've seen, and when we started, people were like, "Do we need to partner it to go from our mouse to our human?" This study, when you have this development path near term, doesn't look any differently than any of our other medicines. We've got a strong biomarker, a genetically validated target, and we can measure outcomes in response to that. I think these data show us today that we can continue to demonstrate not only this in the phase I healthy overweight volunteer study, but really in patient populations with higher BMI, we can run off-ramp studies. I think near term, the focus is to deliver the next datasets and continue to deliver value to patients. On the second one, which I think is another interesting question, is you brought up the competitor data and thinking about other siRNA approaches. I think it's really critical to go back to Erik's introduction and actually go back to research day where Chandra was sharing the incredible work that team's done on the innovation on chemistry differentiation using SpiNA designs for siRNA. I mean, I feel like déjà vu when we said for RNA editing that we have a differentiated approach to delivering best-in-class editing, and everybody said, well, chemistry doesn't matter. Well, I think those data played out. So if we think about the siRNA landscape, I think we're bringing innovation to chemistry that's driving better, more durable knockdown in seeing the only data preclinically in a weight loss setting that shows Activin E reduction. So I think we've seen strong preclinical data showing that our SpiNA designs do potent, durable preclinical silencing that led to loss in fat and preservation of muscle in vivo. And then ultimately, today's data, again, exceeding our expectations that those data translate when we bring a best-in-class chemistry forward. And now, with the safety and convenience of a once to twice-a-year administration, I think we're really poised to disrupt and define the Inhibin E space. Got it. Thanks so much. Thank you. Thank you. There are no further questions at this time. I will now turn the call back over to Dr. Paul Bolno for closing remarks. Thank you, everyone, for joining the call this morning. I'm grateful to every Wave employee for their dedication and focus on our mission and on the patients and families we serve. Have a great day.