Hello, and welcome to Wave Life Sciences positive interim phase I clinical data from INLIGHT trial of WVE-007 for 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. Please be mindful of time and ask one question per raised hand. Also, as a reminder, this conference is being recorded today. I will now turn the call over to Kate Roush, 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 otherwise healthy 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 31st, 2025.
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 Ingelsson, Chief Scientific Officer, will discuss WVE-007, our inhibin E GalNAc siRNA. Dr. Chris Wright, Chief Medical Officer, will present the INLIGHT clinical trial interim data and phase II A update. Next, Paul will review next steps and anticipated milestones before turning it over to Q&A. Dr. Chandra Varghese, Chief Technology Officer, will also be available to answer questions. I'd now like to turn the call to Paul.
Thank you, Kate. At Wave, our goal has been to harness the power of human genetics to develop transformational medicines, leveraging our best-in-class chemistry. Today, we're pleased to share with you significant progress towards this goal with the continued clinical translation of WVE-007, our GalNAc siRNA for obesity. 007 is a potentially transformational treatment for obesity that improves body composition by reducing fat, in particular harmful visceral fat, while preserving muscle.
There are three key takeaways I'd like to highlight from today's update. First, our best-in-class siRNA for obesity continues to demonstrate an industry-leading and highly differentiated profile in the clinic, potent, dose-dependent and durable reductions of Activin E, and a very clean safety profile. Second, 007 continues to translate in the clinic and demonstrate its potential as a novel transformative therapy to deliver fat loss and muscle preservation.
In a phase I study with low BMI and a generally healthy population, we are already seeing substantial improvements in body composition, including a clinically meaningful 14% reduction in visceral fat and a 3.3% reduction in waist circumference six months following just a single dose. The continued fat loss we're observing and concurrent stabilization of muscle also led to weight loss of 1%. Third, as planned, we are quickly advancing 007 to the phase II A portion of INLIGHT in a higher BMI population that includes individuals with comorbidities, which is consistent with other phase II or phase III obesity studies.
These study populations carry more excess fat and will enable demonstration of higher fat loss with continued muscle preservation, leading to greater weight loss, as well as demonstration of clinical biomarkers to inform development in MASH type 2 diabetes and cardiovascular disease. Today, Erik will first remind you of the unique and compelling biology and human genetic evidence that support 007, and Chris will then cover our phase I interim data update and next steps for phase II/a development. 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 that 007 is well-positioned to deliver a truly differentiated novel therapeutic approach. Individuals living with obesity face markedly higher risk of a range of diseases such as MASH, type 2 diabetes, and cardiovascular disease.
Excess body fat, in particular the dangerous visceral fat, is a key driver behind this elevated risk of disease. Current standard of care with GLP-1s and other incretins is focused on caloric restriction by reducing appetite and slowing gastric emptying, and carry many limitations such as muscle loss, frequent dosing, and tolerability challenges, resulting in high discontinuation rates, as well as weight cycling due to individuals coming on and going off therapy.
The consequence of muscle loss is particularly important to emphasize, as skeletal muscle plays an important role in metabolism and weight maintenance. Taken together, there is a large unmet need for therapies that leverage an orthogonal approach to induce fat loss while preserving muscle, enhance efficacy of incretins as an add-on, and maintain weight loss and metabolic improvements after cessation of incretins.
007 improves body composition by decreasing excess fat through adipocyte lipolysis and retaining muscle, and does not lead to or require caloric restriction to achieve these results. With a favorable safety profile that we have observed to date and the potential for infrequent once or twice yearly dosing, we believe that 007 could offer a transformational approach to obesity treatment.
007 is designed to silence inhibin E to lower serum activin E, and compelling human genetic data support our confidence in this mechanism of action. In the U.K. Biobank and other population-based studies, heterozygous inhibin E loss-of-function variant carriers, individuals living naturally with 50% less inhibin E exhibit a healthier overall pro-metabolic profile driven by lower visceral fat, as evidenced by lower waist-to-hip ratio and lower visceral adipose volume, as well as downstream effects with lower triglycerides, ApoB, and HbA1c, and higher HDL cholesterol.
These carriers also have favorable associations with liver traits, such as ALT, a measure of liver damage, and cT1, a measure of liver inflammation and fibrosis, and importantly, lower risk of developing type 2 diabetes and coronary heart disease. By silencing inhibin E mRNA, we aim to recapitulate the protective phenotype seen in these heterozygous loss-of-function variant carriers.
Inhibin E is produced in the liver, where it dimerizes as the hepatokine Activin E. Activin E is released into circulation, where it binds to ALK7 receptors on adipocytes. This blocks adipose lipolysis, the breakdown of triglycerides, promoting fat storage, increasing risk for obesity and cardiometabolic disease. By reducing hepatic inhibin E mRNA with a GalNAc-siRNA, we lower circulating Activin E, leading to a decrease in ALK7 signaling in adipose tissue, releasing the brake on lipolysis, or in other words, increasing metabolism of excess fat, which is ultimately expected to lead to weight loss and lower cardiometabolic risk. Although there is human genetic evidence for both inhibin E and ALK7, further supporting the importance of this mechanism in regulating body composition, we chose to target Activin E through inhibin E silencing over its receptor, ALK7, for several reasons.
Turning off protein production in hepatocytes, the upstream source with a GalNAc-siRNA is the most efficient and durable way to address this mechanism. Further, suppressing the Activin E ligand rather than disabling the ALK7 receptor is a more selective approach with lower risk of unintended consequences, since ALK7 has multiple ligands across different tissues, including reproductive organs. This selectivity is especially important for us as we think about long-term safety, as well as clinical and commercial translation. 007 is highly 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, which enhances interaction with AGO2, stabilizes the loaded RISC complex, and improves liver exposure, all of which contributes to dramatically improved silencing potency and durability when compared with industry-standard siRNA designs, something we have shown repeatedly for inhibin E and other targets.
In addition to strong evidence from human genetics, there is also robust evidence showing that higher circulating activin E levels are associated with a range of cardiometabolic measures, providing further evidence of the importance of this mechanism in development of obesity and cardiometabolic disease in humans. In an observational study of 324 non-diabetic participants, activin E levels were strongly correlated with increased BMI, abdominal fat, and fasting insulin.
This, together with the genetic evidence from the general population, our preclinical data, and our data from the INLIGHT study, all support that the associations of inhibin E and Activin E with body composition are not restricted to individuals with diabetes, but that inhibin E suppression can result in fat loss regardless of diabetes status.
Importantly, the strong correlations of Activin E levels with BMI highlight the opportunity for larger effects of WVE-007 when we move to higher BMI individuals in our phase II studies, which Chris will speak to in more detail momentarily. 007 is designed to improve body composition by decreasing fat while preserving muscle. We expect effects on both subcutaneous and visceral fat as Activin E binds to ALK7 on all adipocytes.
Generally, any weight loss regimen will have a proportionally larger effect on visceral fat, especially at the earlier time points, since this type of fat is more metabolically active, better supplied with blood, and more sensitive to fat-mobilizing hormones. We expect this phenomenon to be even more pronounced with 007 as it acts directly on lipolysis. We expect both visceral and total fat loss with 007 to be substantially larger when studied in higher BMI populations with more excess fat. Visceral fat, which is around your organs, is strongly linked to insulin resistance, MASH, type 2 diabetes, and cardiovascular disease. There is robust evidence supporting that 5%-10% lower visceral fat is associated with decreased risk of a number of cardiometabolic diseases.
Waist circumference is an easily accessible clinical proxy for visceral fat that has also been shown to be strongly associated with cardiometabolic diseases in many large studies. We're already observing more than 14% reduction in visceral fat and more than 3% reduction in waist circumference after 6 months in our 240 mg dose, despite low baseline levels of visceral fat and BMI. While it tends to get less attention in obesity, muscle also plays a crucial role in metabolic health in addition to preserving strength, function, bone density, and longevity and reducing risk of sarcopenia and frailty. For context, with incretin therapy, up to 40% of the weight loss is driven by muscle loss, meaning that the health benefits delivered from fat loss are partially offset by muscle loss.
Skeletal muscle increases basal metabolic rate, the number of calories you burn as your body performs all basic life-sustaining functions, making up about 70% of the calories we burn. Further, higher muscle mass is associated with higher glucose disposal, better insulin sensitivity, and improved overall energy balance, which helps reducing visceral fat and preventing weight regain. Visceral fat and skeletal muscle are the two components of body composition that are most important for cardiometabolic health. As most obesity treatments drive fat loss at the expense of muscle loss, using a metric such as Visceral Fat to Muscle Ratio, or VMR, is a good composite measure of body composition to integrate both the harmful visceral fat and the beneficial lean fat into a single index.
This metric has been used in many scientific publications, and a lower VMR has been shown to be strongly associated with a decreased risk of MASH, type 2 diabetes, and cardiovascular diseases. Our comprehensive preclinical studies underscore our conviction in our potentially best-in-class therapeutic approach that leverages a completely orthogonal mechanism from incretins by inducing fat loss with lean mass preservation. We have shown that our molecules reduce INHBE mRNA and circulating Activin E levels, increase adipocyte lipolysis, and lead to reduction of adipocyte sizes and fat loss, in particular visceral fat. This in turn results in a reduction of inflammation and fibrosis in adipose tissue, as well as improved insulin sensitivity, changes that are likely to contribute to a lower risk of cardiovascular disease and type 2 diabetes.
In our studies in DIO mice, a model that represents severe obesity with an abundance of excess fat, weight loss with an 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 over time, the substantial fat loss is translating to weight loss as the lean mass stabilizes.
The early clinical translation of 007 in INLIGHT fortifies our excitement in other treatment settings, such as add-on to incretins, where we have observed approximately twofold greater weight loss as an add-on to semaglutide versus semaglutide alone in DIO mice. We have also shown an ability to curtail weight regain upon cessation of semaglutide INHBE , providing powerful data for its utility in a maintenance setting. 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, the phase I portion of INLIGHT is a placebo-controlled, single ascending dose study, randomized 3: 1 active placebo with potential to escalate up to five single dose cohorts. It's designed as a safety tolerability PK/PD study. Participants are healthy individuals living with overweight or class one 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 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.
We next evaluated the 240 mg, 400 mg, and 600 mg ascending dose cohorts, including DEXA and other measures. Today's update primarily covers six-month follow-up data from our 240 mg cohort, as well as observations from our 400 mg cohort. In addition, further updates on safety and PK for the 75 mg-600 mg cohorts are provided. We will describe the design of our phase II, a multiple dose amendment to INLIGHT in more detail as well. 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 and 400 mg cohorts. Mean baseline BMI was approximately 32 across the treatment cohorts, consistent with the participants having healthy overweight or class one obesity.
Baseline characteristics showed differences between our 240 mg and 400-mg cohorts, with the 400-mg cohort having lower baseline BMI, lower waist circumference, lower body weight, total fat, and visceral fat with higher lean mass. The difference in baseline visceral fat was particularly notable, as it was 30% lower in the 400-mg group compared to the 240-milligram group. Overall, the differences suggest that the 400-mg cohort had a healthier baseline body composition relative to the 240-mg cohort. To put these baseline characteristics into perspective, here you see a graph showing the U.S. general population distribution of BMI on the x-axis and visceral fat on the y-axis.
The dark blue contour represents where 50% of the U.S. population falls for these measures, and the light blue contour indicates 95% of the population. On this background, we show the baseline BMI and visceral fat levels for our 240 mg, that's in purple dot, and 400 mg in the pink dot, phase I INLIGHT cohorts. The baseline BMI and visceral fat levels, the open dots, typical for phase II and III obesity studies, using the BELIEVE study as an example. As you can see, consistent with phase I obesity studies, baseline BMI and visceral fat in INLIGHT are markedly lower than the baseline levels of phase II and III studies.
The phase II BELIEVE study provides a good example of this, with baseline BMI and visceral fat primarily outside of the 95% population contour in light blue, meaning that the baseline BMI and visceral fat are in the most extreme 5% of the population. Further, baseline levels in the 400 mg cohort are even closer to a healthy population, with average BMI and visceral fat levels near the 50% population dark blue contour.
We continue to observe a favorable safety profile across all cohorts, which is of critical importance for a potential new medicine designed to treat millions of people living with obesity. There were no treatment discontinuations, serious TEAEs, or deaths. All study-related AEs were mild. There were no clinically meaningful changes in lipids, glucose, or other clinical laboratory measurements, including liver function tests through 600 mg.
Following our update in December, we continue to see robust and durable reductions in Activin E. In this chart, the percentage reduction of Activin E from baseline is shown on the Y-axis, with days on study on the X. We're pleased to show highly statistically significant dose-dependent Activin E decreases across all 007 dose levels, with a mean max reduction of up to 88%. Notably, over 70% suppression of Activin E was still observed out to at least seven months, supporting a highly convenient dosing interval of once or twice a year. With this durable Activin E suppression, we're now excited to show a pronounced improvement in body composition observed over time following a single 240 mg subcutaneous dose.
Visceral fat mass decreased from a 7.8% placebo-adjusted reduction at three months to a statistically significant 14.3% placebo-adjusted reduction at six months. Total fat reduction reached 5.3% at six months, and lean mass stabilized. There were also improvements across clinical measures, including a 3.3% reduction in waist circumference and a 0.9% reduction in body weight.
Overall, these data demonstrate that a single dose of WVE-007 can shift body composition towards less visceral and total fat while preserving muscle mass, consistent with our preclinical findings and the underlying human genetics. These results are encouraging as we're starting to see evidence of improvements in clinical measurements, such as waist circumference and weight.
At six months, even after a single dose of 007 in a phase I study of otherwise healthy participants with an average BMI of 32 and no dietary or exercise restrictions. As Erik previously discussed, we believe improvements in body composition will drive meaningful health outcomes. A key indicator of these improvements is the visceral fat-to-muscle ratio, or VMR, which is an established measure of body composition. As Erik described, low VMR is associated with a wide range of health benefits, including increased risk of MASH or decreased risk of MASH, type 2 diabetes, and cardiometabolic disorders.
To benchmark and contextualize our results at this early development stage, we calculated the change or improvement from baseline in VMR for our 240 mg dose of WVE-007 and estimated this for the treatment arms of the phase II BELIEVE study investigating weekly semaglutide and IV bimagrumab, a myostatin inhibitor, in participants with a BMI of 37. As you can see, a single 240 mg dose of 007 is outperforming both high and low semaglutide at the three-month and six-month time points, even in the context of otherwise healthy participants with BMI of 32. This is due to the substantial reductions in lean mass by semaglutide, which adversely impacts its VMR score. The VMR 007 is on par with bimagrumab with convenience of potential once-yearly dosing and favorable safety profile.
What's particularly impressive about these results is that we're able to achieve these improvements in body composition in a phase I study of otherwise healthy participants with mean BMI of 32, compared to phase II and III obesity studies with BMIs of 35 or higher in metabolic comorbidities. On this graphic, when we add the baseline and post-treatment BMI and visceral fat values from the BELIEVE phase II trial, as shown in the green arrows, you see that the INLIGHT baseline BMI and visceral fat are at a level where the BELIEVE study ends after 48 weeks of treatment. Turning to the 400 mg cohort of INLIGHT, we observed placebo-adjusted changes from baseline that were lower than what we observed in the 240 mg cohort at the three-month time point. For example, the visceral fat reduction was 5%.
As I previously shared, the 400 mg cohort had a notably healthier body composition profile. To understand this impact, we performed a post-hoc analysis categorizing participants by baseline visceral fat levels of greater or less than 500 g. 500 g is an established threshold for healthy levels of visceral fat. Importantly, we saw similar statistically significant reductions in visceral fat at three months in both cohorts where the baseline visceral fat was greater than 500 g. The key takeaway is this. These data are highly supportive that baseline BMI and excess visceral fat will drive treatment response magnitude and reinforce our expectation that with high BMI and visceral fat, effects of 007 on body composition and weight should be even greater.
Now I'd like to reorient you back to this chart and mention why the data I've just shared with you are encouraging when we think ahead to the phase II /a portion of our ongoing INLIGHT trial. As this trial will enroll participants with BMI and visceral fat at levels comparable to other phase II and III obesity studies, we expect greater fat loss and total weight loss like what is observed in other phase II and III obesity studies. Turning to the phase II portion of the INLIGHT study, our teams are actively working to initiate this study in the second quarter of 2026. This phase II /a portion will enroll individuals with BMIs in the range of 35-50 and comorbidities with a 3-to-1 active placebo randomization.
Assessments in this multi-dose portion are expected to be similar to those in the SAD portion, with additional inclusion of body composition measured by MRI, liver fat content as measured by MRI-PDFF, HbA1c, lipid levels, CRP, and muscle function. The design and study population enables enhanced evaluation not only of improved body composition and weight loss, but also informs additional opportunities for 007 in MASH, type 2 diabetes, and cardiovascular diseases. The study will enroll two different populations with high BMI, with and without type 2 diabetes, with the diabetic cohort initiating after the start of the first two high BMI cohorts. Participants will be given two doses of 007 at day one and at day 85 and followed for 12 months, with the first major assessment occurring at day 85.
Finally, in addition to investigating 007 in individuals with high BMI and comorbidities, including diabetes, 007's favorable safety profile and ability to drive reductions in fat while preserving muscle with an orthogonal mechanism may support the use of 007 as an add-on to incretins. Within the community, there's 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 this new phase II program is actively progressing, and we remain on track to initiate trials investigating 007 as an incretin add-on and as a post-incretin maintenance in 2026. I'll now turn the call back to Paul.
Thanks, Chris. We're extremely excited about the profile we have observed with 007 in this study population with low BMI. We've demonstrated clinically meaningful improvements in body composition, favorable safety and tolerability, and durability, supporting once to twice-a-year dosing, and we're moving quickly to advance 007 into the next phase of development. In addition to initiating new trials investigating 007 's potential as an add-on and maintenance post-incretin therapy in 2026, we're on track to initiate the phase II /a MAD portion of our ongoing INLIGHT study next quarter in individuals with higher baseline BMI and comorbidities. Here, we'll have an opportunity to evaluate further improvements in body composition in a population with higher BMI, which is much more representative of typical phase II and III obesity studies, with participants having a lot of excess fat to lose.
Therefore, we believe this study population will achieve even greater effects on body composition with substantial fat loss, lean mass retention, leading to the regulatory threshold of at least 5% weight loss. In addition to measures of body composition, we'll also be evaluating improvements on imaging and clinical biomarkers, which will inform 007's potential to impact across additional indications. As a reminder, reducing visceral fat by at least 5% is strongly associated with improving broader cardiometabolic diseases. Therefore, the over 14% reduction in visceral fat six months after a single dose of 007 is highly encouraging. We will be evaluating a number of measures in the phase II/a portion of INLIGHT, including MRI-PDFF, HbA1c, lipid levels, CRP, and muscle function, which will have the potential to unlock indications beyond obesity, including MASH, type 2 diabetes, cardiovascular disease, PCOS, and more.
With 007's ability to improve body composition through reducing fat and preserving muscle, we believe 007 will offer a transformative approach for obesity in combination, maintenance, and as a monotherapy, particularly individuals who are not able to tolerate incretins or muscle loss, as well as for a range of metabolic diseases. With over $600 million in year-end cash and cash equivalents, we are well-capitalized and well-positioned to deliver on multiple milestones with both WVE-007 and WVE-006. We remain on track to initiate the phase II A portion of INLIGHT in individuals with higher BMI next quarter, as well as to initiate new trials of WVE-007 as an incretin add-on and as post-incretin maintenance in 2026.
Also this year, we plan on sharing additional data from INLIGHT, including data from the 600 mg cohort of our phase I study. In the second quarter, WVE-006 remains on track to deliver data from the 400 mg multi-dose cohort and the 600 mg single-dose cohort of RestorAATion-2 at the ATS conference in May, and we expect to receive regulatory feedback mid-2026 on a potential accelerated approval pathway. Before turning the call over to questions, I would like to take a moment to thank everyone participating in INLIGHT, the clinicians involved, and the study site staff. They continue to inspire the work we do every day, and from everyone at Wave, we'd like to express our sincerest gratitude. With that, I will turn it over to the operator for Q&A. Operator?
Thank you. At this time, if you would like to ask a question, please click on the Raise Hand button, which can be found at the bottom of your Zoom screen. You may remove yourself from the queue at any time by lowering your hand. When it is your turn, you will hear your name called. Once you've been called on, please unmute yourself and begin to ask your question. Our first question comes from Steve Seedhouse from Cantor Fitzgerald. Please unmute your line and ask your question.
Hey, good morning. Thanks for taking the question. It's a multi-part one on the dose selection going forward. I was just hoping you could expand on the rationale for the chosen doses, given what you're seeing in this initial data set for the phase II/a, including if you could clarify how frequent you're gonna be dosing. It wasn't clear, if the day 85 visit includes the second dose or if it's gonna be less frequent. Last part of that question is just was the dose selection informed at all by any insight into the efficacy of the 600 mg cohort? Thank you.
No, thank you for the question. The dose selection is informed by two important criteria. One is obviously Activin E reduction. If we think about the dose response, the whole mechanism, as Erik laid out fundamentally at the beginning, is potent, durable suppression of Activin E. We see a dose-dependent suppression. What's interesting is we get to the 240 and 400. The PK is looking incredible for 240. I mean, as we said, we're out now past seven months with suppression, with 400 continuing to accrete behind it. We do believe we have the suppression we need to stay below that 70%-75% threshold across both the 240 and 400. The biggest question is ultimately gonna be what ultimately gives us the potential for once a year dosing.
We'll understand does 240 sustain that as a once a year or is it twice a year, and does 400 give us that opportunity for longer duration. We do believe we've got the Activin E suppression necessary for the dose selection. Safety as well, I mean, we're cleared through 600, so safety is clean across all of the dose cohorts. In terms of the dosing regimen, as you point out in the phase II/a , with durability out past 12 months, we know we've been talking to a number of you about the fact that how long you know, how can we accelerate this MAD study. Our view is we're actually truncating that at day zero day 85. There'll be those two doses in that regimen.
Remember, the phase I study, as we think about PK follow-up, follows these patients over a year. We'll be continuing in this current phase I INLIGHT to be monitoring Activin E levels over that period of time to look at durability, while in the MAD study be able to truncate the distance between those two dose regimens. The MAD will have that shorter interval, and that combined with the phase I will inform the subsequent dosing regimen. Again, we continue to see active durable suppression.
I think to step back, one other piece on dose selection to activity, you know, when we go back to the observational study in over 300 patients where there's that correlation between Activin E, BMI, and truncal obesity, it informs us really well that if we stay at this level of suppression and go into, as Chris showed, that high BMI, higher excess visceral fat population, we do expect substantial continued decreases in both visceral fat from where we already are at the over 14%, total fat and importantly, body weight. Oh, sorry, 600. We will have, as we said, we'll look at the 600 data later. No, the dose selection is not informed by the 600. We'll look at that data to see where that goes subsequently.
Thank you, Paul.
Yep.
Thank you. Our next question is from Joseph Schwartz from Leerink Partners. Please unmute your line and ask your question.
Hi, thank you. I have a two-part question. In a landscape where most therapies drive weight loss broadly, how confident are you that preferential visceral fat reduction will be valued by regulators, physicians, and payers as a differentiated benefit? Is there a specific patient population such as high visceral adiposity, insulin resistance, or sarcopenic obesity, where this mechanism and profile is particularly compelling if total weight loss remains more modest, relative to visceral fat loss? Can you quantify any good base case opportunities for us, recognizing that most investors are not underwriting broader use at this point?
Yeah, I mean, I think to step back is you just define the obesity population in the commercial setting. That's studied in patients with high abdominal adiposity and high excess visceral fat. If we go back to every two, three study, and I think stepping back, we have to remember we're all looking now, as Chris nicely laid out, at a phase I population. To your point, the population that we'll be going into as we think about an obesity therapy has high abdominal adiposity, high visceral fat, and in that reduction, you'd expect to see continued drop in body weight, which is why, again, we've always said in the right dose at a year in the right population, meaning the obese population, we would expect to see the regulatory thresholds.
I think moving down the regulatory thresholds and thinking about reimbursement and what payers pay for, payers pay for outcomes. If we think about what's driving health benefits of obesity therapies, it's driven exactly as Erik said on the danger of visceral fat. Visceral fat is what drives cardiometabolic risk, diabetes risk. Again, the fact that we're seeing levels in a phase I study, low BMI, lower visceral fat than in phase II obesity studies that are exceeding those, like we should be able to have that health benefit play out as part of that therapeutic landscape. That said, to your last question of are there unique populations as we think beyond combo maintenance, that for monotherapy, you know, there's over 30 million people living with obesity who are at risk for muscle loss.
Just as a distinct population within the monotherapy setting, there's people who can't afford to lose muscle from a metabolic standpoint, in addition to frailty. The ability to still achieve high levels of important reductions in fat with muscle preservation is unique to that. That, you know, I think it is really important to say that's assuming that locking in the profile currently on substantial visceral fat in the current study, which is not the study that you do in obesity, which will be in high abdominal fat. Again, we do anticipate in that higher population, the data suggests, the genetics suggests, that we'll see substantially larger effects.
Just to add one more thing as well. As Paul said, when we move into the phase II trial with a higher BMI population, we expect that both the visceral and the subcutaneous fat will continue to go down. The inhibin E 007 binding is happening on all types of adipocytes, and we have already seen effects on both visceral and subcutaneous. We do see that both will continue to deepen in a larger BMI population with more fat excess.
Thank you.
Thank you. Our next question is from Cheng Li from Oppenheimer. Please unmute your line and ask your question.
Oh, hi. Thanks for taking the question. Just maybe two parts. I'm just wondering what may be the best predictor for WVE-007 efficacy, whether it is like baseline visceral fat or it is BMI or maybe it's baseline Activin E level. Just a follow-up question is, just wondering if VMR can be validated as, like, a predictor for a clinical outcome that can be used as part of the registration endpoint. Thank you.
No, thank you. I think you pointed out the important axis. Because if you actually look at the correlation, it's very nice between exactly what you laid out, which is that Activin E levels correlate with higher BMI. The higher BMI as we move into, there are higher Activin E levels. I will say we see very similar data to the population data in our study. Higher BMI correlates to higher Activin E levels. Again, higher BMI, higher Activin E. If you look at that also correlates to higher abdominal truncal obesity, and higher visceral fat. When you put those metrics together and you look to where phase II, III obesity studies run, you improve the metric that's hence the X and Y axis on both BMI.
BMI is a reflection of abdominal adiposity, hence visceral fat, and in that setting of higher excess fat. I do think it's just really important to level set coming into this study, which is why I think people kind of are going, how does this compare? Is that when we have the healthy phase I study with patients living with obesity and overweight, the criteria that caps any of these other effects limits because visceral fat drives additional comorbidities, limits the ability to explore that.
I do think based on actually the response in the 400 and the 240, that this point on visceral fat thresholds and what an excess visceral fat threshold does is actually really validated. We see higher levels of visceral fat tied to those comorbidities driving larger effect size. Again, going to the phase II study in that higher BMI, higher visceral fat population would be expected to drive further efficacy.
Thank you. Our next question is from Alec Stranahan from Bank of America. Please unmute your line and ask your question.
Hey, guys. This is Matthew on for Alec. Thanks for taking our questions. Two from us. First, can you explain how you think about the kinetics of total fat loss, which remained relatively flat between month three and six, and visceral fat loss, which doubled in that same timeframe? Just maybe thinking about how we view that in the higher BMI population, whether we expect the kinetics or magnitude of these changes to be different. Maybe a second quick one, I guess, you know, looking at HbA1c lipid levels, CRP muscle function, have you been tracking these in phase I data? Any comments on how those have looked so far? Thanks.
We'll take the last question first, and then we'll focus on the first. The last one is that those were actually part of the exclusion criteria. To be a healthy, overweight, obese study, patients had to be excluded with changes in hemoglobin A1c, serum lipids or ALT. There's not an ability to see a dynamic effect, hence the subsequent study where we'll have patients with comorbidities, where we will be able to see those dynamic effects. I think what's encouraging on the lipid profile, on the safety side, was that despite the changes, there weren't changes in lipid profiles that would suggest any concern. I think we could use that in that context in the phase I study. Obviously, as we said, that's a core part of the phase II/a assessment.
As we think about the dynamics on fat, as you point out, that's absolutely going to be driven on where you start from. The more excess fat you have, subcutaneous or visceral, the larger the effect size and impact. If you shift the curve up, I would expect the continuation of that distribution, if you look at percentage of fat, the impact on visceral versus subcutaneous fat, that will continue to be in that, imagine that ratio in an outsized effect percentage-wise on visceral fat. That said, subcutaneous fat, which is a larger proportion of the body, when you lose that, will be responsible for further weight loss. If you imagine going up that curve from, you know, again, we started at the end of where the BELIEVE study was and saw these data.
When you pull that back up to a starting BMI that's greater than 35, and in that study, average BMIs in all of the recently reported studies in obesity are around 37. You go up to that BMI benchmarking to that level of visceral fat, we would expect to see the magnitude even on visceral fat, which is impressive as it is after a single dose now, to actually get steeper and deeper.
Thank you. Our next question is from Madison Elsaadi from B. Riley. Please unmute your line and ask your question.
Hi, guys. Thanks for taking our question. Maybe if you can comment, just curious what the percentage of treated patients in the 240 mg arm at six months may have reached, say, 3% body weight. Just trying to understand maybe what that distribution looks like behind that 0.9% number. If we could maybe take a step back and try to understand the path to 5% weight loss that we know investors wanna see. What's the dose, the duration, the population BMI that can get us there? What is the earliest data set you think could demonstrate it? Thank you.
Yeah, I'll take, you know, the last question. I mean, I do think this is why we're accelerating the 2A, as we announced going into this year, that, you know, from the beginning of this study, we've always said this is a phase I safety PK/PD study to look at the impact of 007, Activin E levels, dose suppression. Then because we're gonna be studying it in patients who are living with overweight and obesity, we'd be able to look and measure the impact of fat reduction and obviously body weight, but being able to look at DEXA. I think what these data continue to affirm is we've got a very powerful medicine that reduces fat and preserves muscle.
I think to your point of where that efficacy is gonna be drawn, and that's again, the announcement we made coming into this year, was that's going to be seen like every other obesity medicine in a phase II/III study where patients have high BMI, high visceral fat, and they're in a setting where they have excess fat to deplete. I think again, we're set up and we're poised to be able to see that. Within the individual weight metrics, I mean, that is the number for the cohort, and we haven't broken down and looked at that into the dynamic range, to be able to look at the placebo response. That is the number. I think what's encouraging, it's consistent.
If we look at the change as we think about fat reduction between three months and six months, there's continued progress. It does speak to what we thought, which is going to be important as we go into the high BMI setting, that the initial lean mass plateaus, so you hit that. As long as you have excess fat to lose, and I will continue to remind you, excess fat is what obesity is. This medicine's mechanism of action is reduction of excess fat, visceral or subcutaneous. You need to put patients into a setting where they can have excess fat to lose, which is what's planned for the II/a study.
Got it. Appreciate the color. Cool.
Yeah, no, thank you.
Thank you. Our next question is from Roger Song from Jefferies. Please unmute your line and ask your question.
You can hear me?
Yes. Hey, Roger.
Awesome. Yes, thank you for the update and taking our question. I found this high visceral fat post-hoc analysis very interesting, maybe very informative. Just curious, you see higher visceral fat reduction in this high population. Did you look at the total fat and the weight between the high and the low visceral fat population? How should we think about the dose dependence here between 240 mg and the 400 mg population? Thank you.
Yeah. No, thank you. If we take the second part of the question, the challenge in any obesity study is always powering and having enough sample to look at. The most sensitive measure on a medicine that reduces fat, as we know from all of it, is visceral fat, the first index. As you point out, 500 is not an arbitrary threshold. Just to be clear, 500 is the threshold of kind of what's defined as excess visceral fat. By crossing into the excess visceral threshold, i.e., having more excess fat to lose, that's where that separation occurs. Once you get past that, it's very hard to pull out with the noise other signals beyond where we have sensitivity.
What it does tell us, and this again informs the II/a study, is if you look at that graph that we put out on BMI and visceral fat, once you get up to the BMIs and in that study, you'll see that it's well in excess of the 500-gram threshold of where you need to see a reduction in fat. I missed the second question. Was there-
Yeah. Maybe just to add, Roger, you mentioned that you found it interesting. We also found it very interesting and encouraging because it really emphasizes that, you know, this approach and this therapeutic really works as it's supposed to do, right? Like, if you have excess fat, there is an opportunity to burn that through increased lipolysis. So it's highly encouraging as we now move into the II/a study with higher BMI and much more excess fat to act on.
Oh, your question on dose dependency. I think we have to think about what—how do we define dose dependency? The first part of dose dependency on a medicine whose mechanism of action is the reduction of Activin E, right, the central ligand in all of this is we do see a dose-dependent reduction. What we see is that as you compress because of potent durable selection, we're right at that inflection point across doses.
We do see the dose dependency, but what we see is that the determination ultimately comes down to fat and the ability to have excess fat. Therefore, we think about the dose dependency on excess fat. The more excess fat you have to lose, the greater effect size you're gonna see across the cohorts without having to necessarily push the dose. I think, again, the benefit of the II/a study, where we are going to take 240 and 400 both forward, is we'll be able to look at that effect size on a duration construct between those two.
Got it. Thank you.
Yeah.
Thank you. Our next question is from Salim Syed from Mizuho Securities. Please unmute your line and ask your question. Apologies. He seems to have lowered his hand. We will go to Luca Issi from RBC Capital Markets. Please unmute your line and ask your question.
Oh, hi team. Thanks, and congrats on the progress. Thanks so much for taking our question. This is Cassie for Luca. For weight loss, could you help us characterize what's happening in the placebo arm just on the weight loss part? We know in other obesity trials, patients can be receiving, you know, lifestyle management instructions, and that might help them lose weight there. Any color on how we see that is very helpful, and if we can ask another one on the visceral fat.
The impact of baseline body composition makes a lot of sense, and going forward, do you anticipate setting sort of a minimal visceral fat threshold in your inclusion criteria? What is the thinking on the proportion of obese patients have visceral fat over 500 and above overall? Is the profile closer to the 60% that you see in your 400 mg, or it can be higher? Any color there much appreciated. Thank you.
No, thank you. I'm gonna work backwards from that. What's interesting is, and it's a very good question 'cause it's the one where we put our head on making sure that when we design the II/a study in a medicine that reduces fat, how sure are we going to be that we've captured that population? Actually, the data and the analysis we did on both BMI and waist circumference inclusion criteria will put us in the same box as others. We do fully expect that the study will look like other phase II/III studies. When you look at the disposition of patients in those phase II/III studies, they're well in excess of that 500 g of visceral fat.
You know, again, it's why we kind of put the graph there 'cause it's a nice way to get a sense visually of where we expect these patients to cluster on that study. If you imagine that patient population with high abdominal adiposity, there's a big impact for visceral fat reduction beyond the over 14% we're seeing, but importantly on subcutaneous fat and ultimately with muscle preservation, that leads to weight loss. Again, the conviction is high based on the patient population. That's what we see across studies. There are no diet and exercise requirements in this study. Again, that placebo-adjusted weight are the best way to visualize a study because there are dynamics in that.
Again, it was important for us that we do see that weight loss is coming because I know there were a lot of questions coming up. What's happening with lean mass? Is lean mass gonna stabilize? Is fat loss going to eventually lead to weight loss? Not just for this study, but importantly, how would we imagine the impact of that back in the phase II/a study? Absolutely, I mean, consistent with what we've been saying for a very long time now, in the patient population, which is reflected in that right box of an obesity patient population where we can substantially reduce fat and preserve lean muscle, we would anticipate weight loss in the regulatory framework and lens.
I think, you know, we would expect the majority and not really all the patients in the obesity study, when you look at baseline characteristics from other studies, to have high degree of abdominal adiposity and visceral fat, where we would expect to see an effect size.
Thanks, Paul. That's very helpful.
Thank you.
Thank you. Our next question is from Salim Syed from Mizuho Securities. Please unmute your line and ask your question.
Hey there. Hey, guys. Hopefully you can hear me this time. Thanks for the question. Paul, just one from us. I know you're talking about the framework, you know, the 5% that the regulators wanna see, but I presume you're also speaking to the regulators about body composition and trying to get them to be perhaps more vocal about why that matters. You know, I think that would certainly help Wall Street, you know, with the body composition lens. Is that something that you're actively speaking to them on? Do you have any sense on the path and when they could perhaps get more vocal here? What are they looking for to get more vocal?
We don't comment on direct interactions with the agency, but I will say you are correct. I mean, the agency is focused on body composition. Even in the most recent guidance that they put out last year, there was this reflection on weight loss, with the caveat is the recognition that it's really body composition changes they wanna see. I mean, this race to the bottom where weight loss is driven off of lean mass is recognized, if you ask. There's a focus on building muscle, building protein, and that's very important among the current administrators in Health and Human Services. I think there's a lot of alignment between what's driving benefit.
I think it's super important to remember that visceral fat. When we talk about obesity and the driver in obesity, it's visceral fat that drives the complications in health and health outcomes. Again, that's what payers are paying for. When CMS and other things go, "What do we pay for?" It's paying for outcomes. The advantage that we expect to see where we already are in this low BMI, low setting, which is kind of incredible. A single dose, 240, six months later, we're taking visceral fat back down to levels that exceed kind of that 5%-10% threshold that you'd wanna see to see change in outcomes. We see that.
We are encouraged to have those conversations with regulators on what's gonna ultimately drive it, but also not having to concede the fact that with substantial reduction in visceral fat and on subcu fat in that phase II population, greater than 5% weight loss to hit a weight loss threshold is not taken off the table. Where the conversation should be, if we put weight loss aside, we know clinicians and patients wanna see leaner, not lighter. Scale weight's less important than body composition. We're having a huge impact on the area that people are focused on and including the regulators.
You know, we're excited to bring these data where, again, we're already exceeding what's in the literature for now over decades of 5%-10% visceral fat being tied to bad outcomes, bring these data and have these discussions with them on subsequent studies.
Okay. Got it. Thank you so much.
Thank you. Our next question is from Bill Maughan from Clear Street. Please unmute your line and ask your question.
Good morning, and thanks. Just to put a finer point on that, how firm do you expect the 5% weight loss to be the eventual registrational endpoint? I know, in your previous answer, you talked about what patients and regulators want to see, but could that convert into an actual registrational pivotal study endpoint? Then second, on the three use cases that you discussed, mono, add-on, or maintenance, is monotherapy now probably the least likely eventual commercial presentation, or do you still see that as sort of a beachhead in the market? Thank you.
No, thank you. I mean, I'll take the last question first 'cause I just think it's really important. I think the obvious, which is I think, you know, what you're reflecting on, is combination and maintenance are two key aspects of this medicine, right? The ability to see, particularly given the safety profile, so you're not adding on additional safety on top of the existing therapy. We don't see change in good safety tolerability. I think those become obvious. You know, we've had companies suggest, you know, maybe you start with inhibin E, and then you can actually titrate incretins depending on what patients need. There are a variety of ways of thinking about add-on maintenance, and we think that's interesting.
I think as we pull back and say, what does mono mean, I think to understand where we're going to be is why we're running the phase II/a monotherapy study. I think these data don't. Again, these are phase I data. Everyone, including some of our peer companies in biotech who've shared recent INHBE data, are sharing patients with BMIs of 37. Again, these data are low BMI patients in a healthy study, and this is an early obesity study. I think we need to wait and see what II/a obesity data looks like, where we do inspect larger impact on visceral subQ fat, impact on weight loss, to really define the profile.
Within that profile, we do recognize within monotherapy, like I said, there's about 30 million patients who are living with obesity who are intolerant to or can't tolerate, that or potentially 40% reduction in muscle mass. That population is already thought to be segmented at a certain point in time, and I think a profile with substantial fat reduction, and particularly visceral fat, will find a place in that monotherapy market. I think we need to wait until we have II/a obesity data in order to define where that sits relative to other obesity products.
Thanks. On the registrational endpoint?
Sorry. Yeah, no. To Salim's question, I mean, that is an area that you would imagine that we're very focused on. Again, putting the 5% and not taking that off the table, I do think that that's an arbitrary number. The most important thing when you're and truly, I think part of the reason people are throwing out 5% is there's a back calculation of fat reduction that's tied to that, what the impact on these therapies might be to visceral fat. This is where, as both Chris and Erik alluded to, the VMR, and being able to look at an index that is correlated to cardiovascular management and diabetes, which really looks at the impact of both visceral fat, so bad fat, harmful fat, excess fat, and lean mass preservation, actually gives a tool.
You know, we've had several clinicians that we've been speaking with recently who actually think that's a really viable way 'cause it's not a complicated measurement to look at somebody's visceral fat, which is already calculated, and their lean mass to determine some sort of comparable ratio of how patients are doing on a weight loss journey that ultimately protects body composition. We think that conversation in the setting with supported in literature with regulators would actually be a really powerful way to actually codify and quantify the impact on body composition.
Thanks.
Thank you.
Thank you. Our next question is from Michael King from Rodman & Renshaw. Please unmute your line and ask your question.
Thanks for taking the question, guys. I think we pretty much covered everything, but Paul, just in the answer to your last question, I think I know the answer to this, but just wanna get confirmation from you, which is what, you know, what are the gating factors or factor that, you know, you'll need to proceed past to get start combination studies with incretins?
Yeah. I think that planning is underway, and the way we've designed our submission protocol on the II/a will get us some feedback that will inform how quickly we can get that started. I think our conviction is high, obviously, on the II/a study starting soon, but I also have good conviction on the combo and maintenance study. I think all three of those this year become important components to really address the prior question, which is how to think about this in the three treatment settings, monotherapy, add-on combination, where there's a powerful way of thinking about this given the impact on visceral fat and, you know, where we think the payer will be on that, and maintenance.
If I could just quickly follow up on that, do you feel like you wanna be sort of agnostic to which incretin you combine with, or do you wanna you know, do you wanna go with the most powerful one? Do you wanna go with the orals, the injectables? There's a lot of different permutations that one could envision here.
We've been having that conversation internally, and there are a lot of folks who've been talking to us about ways in which incretins they would prefer us to work with. I think in general, we're gonna make that determination when we share the ultimate study. I think there's a lot of options, particularly on the injectable side. I mean, I think that's an opportunity there, because I think they're well-validated.
Again, we run a study, we wanna have the data be able to be reflective on them where the experience and particularly when you're looking at the effect of two medicines together, where there's a very good understanding of the impact of what you're combining with, so that signals aren't overlapped and you can really discern the impact of your product. Again, you'd imagine we're spending a lot of time with folks on that.
Okay. Thanks so much.
Thank you. Our next question is from Whitney Ijem from Canaccord Genuity. Please unmute your line and ask your question.
Hey, guys. Can you hear me?
Yes.
Okay. Thanks for squeezing me in. Just a couple of quick points of clarification. For the additional data we'll be getting later this year, should we be expecting, like, nine-month data from 240 and six months from 400, et cetera, like assuming every three-month cadence? Is the first question. The second question is, have you looked at the baseline characteristics for the 600 mg dose and have any comments, I guess, on BMI and visceral fat there relative to the 400 mg cohort?
Yeah. I'll take the last question. Again, we haven't evaluated the 600 milligram cohort yet, but given the inclusion criteria and how patients are dispositioned across the study data, I wouldn't expect it to look differently than the current disposition across patients. We'll see that data. Again, to your point on data updates and cadence, the 600 mg data will come as will other updates. I think our guidance right now is these data continue to accrete, and we'll provide opportunities over the course of 2026 to share those data because I think it'll be informative to us and others. The most important data, which is kind of where I don't want to reflect, is as we've just seen. I mean, we're getting super high levels of fat reduction in patients who don't have a lot of fat to lose, right?
These patients don't have excess fat. The most informative data in INLIGHT is going to be the second portion of INLIGHT, which is phase II/a, and that's where we're gonna be able to provide updates on when that study gets up and running too, and when we expect data. Again, in those higher BMI patients, which are going to be much more reflective of all of the great questions of, you know, what happens in that setting, we're going to have the answers to those. Based on all of the modeling and prediction, it all net gets better when you have excess fat. I think we're gonna have a lot of data over the course of 2026. They're gonna continue to inform the profile of inhibin E with the realization that we're talking about a potent, durable medicine on Activin E.
I think well, it's easy to kind of stay focused on, and I get it, we focus there a lot too, on what that downstream effect is on fat. The most important starting point is, do you have a potent, durable suppression of the Activin E ligand with which to see that effect? I think there were a lot of questions, you know, over a year ago, is what does Activin E suppression look like? It's a challenging target for a number of companies to keep durably suppressed.
I think we kind of go back to the most fundamental and foundational part of the data set. We've got safe, durable suppression of Activin E. We can look forward and say, what's the impact in this low BMI setting? That checks the box that we feel very confident about going to the high BMI setting, and that's where we should be able to create the comparisons to other obesity therapies.
Great. Thanks.
Thank you.
Thank you. Our next question is from Samantha Semenkow from Citi. Please unmute your line and ask your question.
Hi. Good morning, and thanks for taking the question. Just in the phase II/a , with the addition of the second dose, is the expectation there to drive further reduction in Activin E with that dose, or is it longer durability of that initial reduction? You know, I guess you've already talked about the 70%, 75% that you want to stay under. Is there a target Activin E dose that you believe will maximize the fat and weight loss with this potential mechanism? Thanks very much.
No, thank you. One, I think we're there. I mean, I think the key here is getting to higher excess fat, and then that's where we're gonna see the change. I think the dosing regimen, as you're pointing out, is gonna teach us just a lot about the suppression. I mean, if you look at the curves, as soon as we give the single dose, that there's a rapid decline in Activin E levels. We'll see. I mean, that it's gonna. I'd say anytime you study something, you're gonna have an opportunity to really look at the impact of that on Activin E suppression. But really, it's gonna help us as we think about long-term dosing regimens, and again, focus on the potential for once a year, what that ultimately looks like.
Between the continued 12-month follow-up with the current dose cohorts, we're gonna learn a lot there, particularly in Activin E suppression. Then in the MAD, that'll continue to inform us. Between those two studies, that'll ultimately define a dosing regimen for a phase III registrational study.
Thank you. Our next question is from Srikripa Devarakonda from JonesTrading.
Hi. Can you hear me now?
Yeah.
All right. Sorry if I missed this, but can you just give us an explanation for the change between December reporting and today's reporting, the three-month reductions in visceral fat and total fat mass? Is that a change in the full placebo comparator? Just one more on timing. Do you anticipate that three-month phase II/a data could be achievable within 2026, given a 2Q 2026 start?
I'll let Chris take the first, but a short answer is yes to your pooled placebo. Yeah.
Yeah. It is the pooled placebo and also that goes into, like, an overall model of all the data. We have all the data from December in the model, MMRM, and also which includes additional placebo participants that were recruited in that time. That's the reason.
Which is an important way to do the statistics on the study is as you accrete new placebo patients to make sure they're incorporated. To your last question, I mean, it's highly encouraging. If we get this study up, as you noticed when Chris presented, we'll have that three-month follow-up time. We do see that to the prior question on the dosing regimen. We do think that single dose initially is sufficient, right, as we think about potential once a year, twice a year therapy. We will have an opportunity within the II/a study at an earlier time point to be able to assess the impact on higher BMI patients as it relates to body composition and weight.
Okay. Thank you.
Yeah.
Thank you. Our final question comes from Ananda Ghosh from H.C. Wainwright & Co. Please unmute your line and ask your question.
Hi. Thanks, guys. One question regarding the VMR comparison, just wanted to know how comparable is the BELIEVE and INLIGHT trial to do a head-to-head comparison?
Yeah. It gets back to the. It's a wonderful way. I think to reflect back again on we've got BMIs of 32, right? If we think about where our patients are proportionally. It's the direct comparison of where we're starting where those BELIEVE study patients are ending on their treatment. When you compare our patients and where they're starting after treatment to the BELIEVE patients, recognizing that they have more abdominal visceral fat, they have more subcutaneous fat, they have higher BMIs, we're still outperforming semaglutide on the VMR index, right? Which does speak to this improvement of body composition in a phase I study in low BMI patients, on par with bimagrumab.
Hence not the equivalency we think long term because when you take our patient population and you bring them back up to the top of the curve where there would be comparison, we'd expect to see even larger impacts on visceral fat, and subcutaneous fat with that higher starting point. It is really important that while these comparisons are done, they're being done from a different patient disposition. Our patients, lower BMI, healthy, no comorbidities, no diet exercise as part of the study. Again, I just kind of reflect on these patients got a single shot, and in six months, without a diet exercise regime that's put on them, lost visceral fat in a consequential way and began to lose body weight.
These patients and most importantly, the 3.3%, we spent a lot of time with questions on body circumference. I mean, this is patients also able then to tighten a belt buckle. Just to put the, you know, the visualization into what's happening in this low BMI healthy population, again, we're highly encouraged going into the two-way study, which everyone else is looking at to see, and outside the fact.
Thank you.
Thank you.
Thank you. There are no further questions at this time. I will now turn the call back over to 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.