Q2 2026 Wave Life Sciences Ltd Earnings Call

Speaker #1: Hello, and welcome to Wave Life Sciences' second quarter 2026 earnings call. We ask that you please hold all questions until the completion of the formal remarks, at which time you'll be given instructions for the question-and-answer session.

Speaker #1: Also, as a reminder, this conference is being recorded today. I will now turn the call over to Kate Rausch, Vice President of Corporate Affairs and Investor Relations.

Speaker #2: Thank you, operator, and good morning to everyone on the call. Earlier this morning we issued a press release outlining our second quarter 2026 earnings update.

Speaker #2: Joining me today with prepared remarks are Dr. Paul Bolno, President and Chief Executive Officer; Dr. Eric Ingelsen, Chief Scientific Officer; Dr. Chris Wright, Chief Medical Officer; and Kyle Moran, Chief Financial Officer.

Speaker #2: The press release issued this morning is available on the Investor section of our website, www.wavelifesciences.com. Before we begin, I would like to remind you that discussions during this conference call will include forward-looking statements.

Speaker #2: These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements.

Speaker #2: The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings. We undertake no obligation to update or revise any forward-looking statement for any reason.

Speaker #2: I'd now like to turn the call over to Paul.

Speaker #3: Thanks, Kate, and good morning to everyone joining us on today's call. At Wave, we are focused on harnessing the convergence of deep genetic insights with our proprietary chemistry to rapidly advance a pipeline of transformational RNA medicines.

Speaker #3: Over the past decade, we have built the most sophisticated and broadly enabled oligonucleotide platform in the industry. Multiple clinical datasets now demonstrate our ability to rapidly advance programs from novel genetic target to proof-of-mechanism in the clinic.

Speaker #3: Our proprietary chemistry is what differentiates our pipeline and distinguishes our molecules from others in the field. In the first half of 2026, we delivered multiple positive datasets across our RNAi and RNA editing pipeline led by WVE007 for obesity and WVE006 for AACD, positioning us to advance both programs to their next stage of development.

Speaker #3: We also continue to progress our second RNA editing tenet, WVE008 for PNPLA3 liver disease, and remain on track for a CPA filing later this year.

Speaker #3: In March, we shared positive data from the single-dose phase one portion of the IN LITE trial of 007 in obesity. These data fortified our conviction in a best-in-class siRNA design with robust and extremely durable silencing demonstrated in the clinic, supporting potential dosing of once or twice a year.

Speaker #3: Also, even in this otherwise healthy population, a single dose of 007 led to substantial reductions in visceral fat and subcutaneous fat without muscle loss or other adverse events associated with increased therapy.

Speaker #3: We have three opportunities to explore in the next phase of development for this program. First, evaluate WVE007 in a phase two A population with higher BMI and comorbidities typical of other obesity trials.

Speaker #3: To demonstrate 007's potential in obesity, as well as evaluate biomarkers to unlock other cardiometabolic indications including MASH and type 2 diabetes. Second, evaluate combination with incretin, which has the potential to deepen weight loss and enhance metabolic benefits.

Speaker #3: Third, and perhaps one of the most exciting and unique opportunities, evaluate maintenance therapy, which would represent an entirely new commercial frontier enabling patients an off-ramp for their GLP-1s.

Speaker #3: We often hear from patients about the fear of weight regain post-cessation of incretins. Up to 70% of patients discontinue GLP-1 therapy within the first year of treatment, and for many it's due to challenges that WVE007 may address, including tolerability issues, treatment burden, or anhedonia, loss of joy, among others.

Speaker #3: In this maintenance setting, 007 would have the potential to enable individuals and payers to realize the sustained health benefits of fat loss and improve body composition for the long term.

Speaker #3: Over the past quarter, the FDA accepted the phase two A IN LITE trial amendment, and dosing is now underway. The phase two A is enrolling individuals living with obesity with BMIs between 35 and 50, and comorbidities with and without diabetes.

Speaker #3: These patients are expected to have higher total body fat and higher levels of visceral fat than the phase one otherwise healthy patients. With this multi-dose clinical trial, we are evaluating our target patient population and have the potential to deliver further improvements in body composition, meaning weight loss, driven off of fat loss without muscle loss, as well as other improvements in cardiometabolic biomarkers, including liver fat, and HbA1c.

Speaker #3: We are also working expeditiously to initiate the additional phase two trials of 007 in combination and maintenance settings this year. Collectively, our development program has the potential to redefine the treatment landscape in obesity.

Speaker #3: In RNA editing, we delivered data supporting 006's potential to offer in new standard of care for individuals living with AACD by treating both lung and liver manifestations of the disease.

Speaker #3: And restoring the dynamic AAC protein response with convenient, infrequent subcutaneous dosing. We are planning to engage the FDA as the agency has granted our request for a meeting to discuss a potential accelerated approval pathway for WVE006.

Speaker #3: This meeting is expected at the end of summer, and will help inform our registrational plans and path toward bringing a much-needed new treatment option to the 200,000 individuals in the U.S.

Speaker #3: and Europe living with homozygous ZZAACD. As a scalable, infrequent subcutaneously dosed oligonucleotide therapy, 006 would offer a potentially differing value proposition for both healthcare providers and payers.

Speaker #3: Current IV augmentation standard of care does not have any impact on liver manifestations of the disease, while investigational DNA editing, in addition to any safety concerns, would be associated with payer challenges for one-time costly therapy with uncertain durability and multi-year enrollee retention.

Speaker #3: Building on our RNA editing success, we are advancing our second RNA editing candidate, WVE008, toward the clinic this year, for PNPLA3 liver disease. 008 aims to address an area of high unmet need with 9 million individuals living with homozygous PNPLA3 I148M liver disease.

Speaker #3: Human genetic data demonstrates these homozygous individuals have about a ninefold higher risk of dying from liver disease as compared with non-carriers. The landscape of therapies and development for this target has been narrowed by recent clinical demonstration that silencing approaches do not address the disease and may actually exacerbate it.

Speaker #3: An RNA editing approach is the only way to restore the functional protein and offers a potential for a novel infrequently dosed therapy with strong support from human genetics.

Speaker #3: Beyond our lead, RNAi and RNA editing programs we continue to push the boundaries of innovation with our proprietary chemistry. We are planning to host our annual investor day in the fall to shed more light on our latest platform advancements and work on our bifunctional modality.

Speaker #3: At the start of the year, we outlined our pipeline priorities. WVE007, 006, and 008 demonstrating our core focus on RNAi and RNA editing, as well as our intent to seek partnership opportunities for HD and DMD.

Speaker #3: Given the evolving regulatory and commercial landscape in DMD, we are exploring potential partnerships in advance of filing an NDA for N531. We continue to believe in N531 and 003's potential as best-in-class treatment options, and look forward to continuing our partnering discussions.

Speaker #3: With our continued success in the clinic and robust balance sheet, we are well positioned and well capitalized to bring our pipeline of potential first and best-in-class candidates to the next stage of development, as we reimagine what's possible for patients.

Speaker #3: Now I'd like to turn the call over to Eric, who will discuss 007 and how we are leveraging our proprietary chemistry and human genetic insights to advance a transformative approach for obesity and other cardiometabolic diseases.

Speaker #3: Eric.

Speaker #2: Thank you, Paul. I'll start today by discussing our innovative gamma SRNA, WVE007, and how our program aims to fill a large unmet need with a differentiated approach grounded in human genetics.

Speaker #2: Today, there are over 1 billion individuals living with obesity globally, including 175 million in the U.S. and Europe alone. These individuals face markedly higher risks of a range of diseases, such as MASH, type 2 diabetes, and other cardiometabolic diseases.

Speaker #2: Excess body fat, in particular visceral fat, is the key driver behind this elevated risk of disease. While there are several therapeutic options available for weight loss, and countless more in clinical development with similar modes of action to those already on the market, these therapies come with several limitations.

Speaker #2: Current standard of care therapies reduce body weight through both fat loss and muscle loss, and they carry high discontinuation rates due to the GI side effects.

Speaker #2: Limiting potential for long-term health benefits. The loss of muscle assists with current weight loss therapies is substantial, with up to 40% of the total weight loss.

Speaker #2: This has significant health implications, as skeletal muscle in addition to muscle strength and function also plays a key role in metabolism by sustaining basal metabolic rate, glucose disposal, and insulin sensitivity.

Speaker #2: Muscle also prevents weight regain, which occurs mostly from fat, in a majority of individuals that discontinue increased therapies. Remember, as much as up to 70% of individuals discontinue incretins within the first year of treatment.

Speaker #2: In ideal obesity therapy, you should instead selectively reduce excess fat, including harmful visceral fat, the fat surrounding one's organs, that is most strongly linked to MASH, type 2 diabetes, and other cardiometabolic diseases, while also lowering subcutaneous fat and liver cytosis, and critically, preserve skeletal muscle.

Speaker #2: It is well established that a 5 to 10% reduction in visceral fat mass is associated with positive health outcomes by reducing risk of multiple preventable metabolic diseases and preserving patient function and quality of life.

Speaker #2: All these benefits can be delivered by 007's mechanism of action. Rather than acting on appetite, 007 silences innovative and lowers serum activity, a liver-derived hepatocyte that signals adverse sites to put the brakes on lipolysis.

Speaker #2: Removing those brakes drives fat loss without calorie restriction and without the muscle loss seen with incretin-based therapies. Our innovative approach is strongly grounded in human genetics, as carriers of heterozygous innovative loss of function variants, Nature's own knockdown experiment, exhibit a healthier overall metabolic profile.

Speaker #2: As Paul discussed earlier, 007's unique ability to durably suppress innovative is driven by our proprietary chemistry and STINA SRNA design. Our next generation STINA designs enhance interactions with HELA-2, stabilize the loaded risk complex, and improve liver exposure, all of which contribute to dramatically improved silence impotency and durability when compared with industry-leading SRNA designs something we have shown repeatedly for innovative and other targets.

Speaker #2: While RNAi is a well-established therapeutic modality and there are extensive human genetics data supporting innovative as a target, we believe our proprietary chemistry distinguishes us from others attempting a similar approach.

Speaker #2: Our interim phase one in life data sets from lower BMI, otherwise healthy individuals confirmed that this proprietary chemistry and the underlying human genetics are already translating in the clinic.

Speaker #2: We have observed consistent durable and dose-dependent serum activity reductions of up to 88%, which were sustained through at least seven and a half months, supporting 007's potential for once or twice-yearly dosing.

Speaker #2: Notably, we observed the translation of target engagement to substantial improvements of cardiometabolic risk factors, with preservation of lean mass and clinically meaningful reductions in total fat, visceral fat, and weight circumference after just a single dose.

Speaker #2: To provide context for our results at this early development stage, we calculated the visceral fat and muscle ratio, or VMR, which is a measure of body composition that integrates harmful visceral fat and beneficial lean mass into a single index.

Speaker #2: Lower VMR is associated with a decreased risk of MASH, type 2 diabetes, and cardiometabolic disorders. With a single dose of 007 in our phase one population, we already observed a 16.5% improvement in VMR, which was more than 12.2% achieved with weekly semaglutide in the phase two belief study and approached the 18.8% observed with VMR.

Speaker #2: We believe VMR has the potential to serve as a novel composite biomarker that captures body composition improvements more holistically than BMI, and that may better predict long-term clinical benefits.

Speaker #2: Together with the patient community and KOLs, we're working to engage with regulators on the importance of improving body composition. Including decreasing excess fat and preserving muscle consistent with their recent guidance.

Speaker #2: What makes the comparison with the belief study particularly exciting is that our in life participants had substantially lower baseline BMI, lower visceral fat, and lower total fat compared to phase two and phase three obesity studies, including the belief study.

Speaker #2: Clinical experience also highlights the importance of baseline adiposity. Early phase one studies in leaner individuals typically show more modest fat reductions. While studies of individuals with higher baseline obesity demonstrate substantially larger decreases in total and visceral fat mass.

Speaker #2: Early follow-up from our 400 milligram cohort, which included a substantially higher proportion of individuals with low levels of body fat, also confirmed that higher baseline visceral fat, lead to greater visceral fat reductions overall.

Speaker #2: As Chris will speak to shortly, we've been working expeditiously to advance 007 into participants with higher BMI and comorbidities, in the phase two A portion in light, where existing science predicts a larger effect.

Speaker #2: Activity binds out seven on all adipocytes, and visceral fat being more metabolically active and better perfused mobilizes first, exactly what we have observed in phase one, with more excess fat to lose, we expect both visceral and total fat loss with 007 to be substantially more pronounced in higher BMI participants in the two A study.

Speaker #2: For further detail on our 007 development plans and our RNA editing programs, I'd now like to turn the call over to Chris.

Speaker #1: Thanks, Eric. As you recently announced, we're excited to have advanced 007 to a population well suited to its mechanism of action. We would expect even more pronounced effects on visceral and subcutaneous fat loss.

Speaker #1: Dosing is currently underway in the phase two A multi-dose portion of in life. This global placebo-controlled trial will enroll individuals with higher BMIs in the range of 35 to 50 and comorbidities across two dose levels, 240 milligrams and 400 milligrams, and two study populations, with and without type two diabetes.

Speaker #1: For a total of four cohorts of 40 patients each. Assessments in this multi-dose portion are like those in the single dose portion, with additional inclusion of body composition measured by MRI, liver fat content as measured by MRI PDFF, HbA1c, lipid levels, and other measures.

Speaker #1: 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 NASH, type two diabetes, and cardiometabolic diseases.

Speaker #1: Participants will be given two doses of 007, one at day one and one at day 85, and followed for 12 months with the first key assessments occurring at day 85.

Speaker #1: We believe that 007's orthogonal mechanism, ability to drive fat reductions while preserving muscle, and favorable safety profile are also aptly suited to combination and maintenance approaches.

Speaker #1: Our preclinical disease. Approximately 200,000 individuals in the US and Europe live with homozygous PIZZAATD. Currently, the only approved treatment for AATD is weekly IV plasma-derived augmentation therapy.

As an add-on to include in versus increment alone. In obese, mice and have demonstrated the ability to curtail weight regain following cessation of increase.

Planning is well underway. For clinical studies, addressing incret combination and post-impact to initiate this year.

We also expect to share additional data from the Phase 1 portion of INHIBE, this year, including data from our 600 milligram cohort, which will further inform the durability of 007.

turning to our ongoing restoration to clinical trial of wvo ships for aatd

ADTD is a uniquely compelling disease for RNA editing.

It is a monogenic disorder caused by a single. Well, characterized genetic variant and the serpina1 gene

This leads to misfolded, GAAT protein and an absence of healthy circulating MATT protein, which normally protects the lung during inflammation or infectious events.

Without Dynamic production of functional a protein individuals with alpha 1 are at risk for lung damage and ultimately developing empyema and bronchi ecosys, which is characterized by chronic cough, recurrent infections, and shortness of breath.

In parallel, misfolded, zat. Accumulates in hatay and causes Progressive liver injury and increased risk of liver disease.

Speaker #1: Which carries several limitations. With a fixed scheduled dose, there's no restoration of dynamic response, leaving individuals with alpha one at risk if AAT protein levels fall too low during an infectious or inflammatory event.

Speaker #1: IV therapy is time-consuming, and often requires inpatient visits, and does nothing to lower ZAAT to address the risk of liver disease. Investigational therapies and development also come with several limitations.

The risk of irreversible off-target effects is particularly notable as genomic. DNA editing has been connected to editing and cancer Associated genes.

Also, in development are a at SI RNA approaches which reduce vat. However, they do not restore, Matt potentially exacerbating lung disease, through chronic AET knockdown,

06 has the potential to be the first treatment for aatd. That enables an individuals with alpha 1 to produce protective a protein when needed most and address. The root causes of the disease where the convenient and infrequent, subcutaneously dose therapy

With 06, our goal is to recapitulate, an MZ like phenotype as it's well established that heteros. Individuals have low risk of both lung and liver disease.

MZ individuals, compared to diseases have reduced levels of zat, which protects the liver from damage and are able to protect the lung with basil. Aat levels above 11 micromolar of which at least 50% is wild type. And the at

And most importantly are able to mount a dynamic, a response during an acute infection.

That combination.

G, a reduction protective basal level is a meaningful proportion of wild-type MAT, and a preserved acute-phase response is the bar we set for 0.6.

As we shared in May, this is exactly the profile we've consistently achieved.

WV6 delivered a compelling therapeutic profile following only three months of treatment across both 200 milligram bi-weekly and 400 milligram monthly dosing.

Importantly 06 RNA editing, uh the the os6 RNA editing approach produces only wild type canonical. Matt and does not include bystander, edited ISO forms as seen with DNA editing,

But may also render patients ineligible for future base editing or RNA editing therapies.

Enrollment and dosing are now complete in the 200 milligram, 400 milligram, and 600 milligram cohorts of RESTORE2, and we remain on track to share data from the 600 milligram monthly dosing cohort in the second half of this year, which will help inform an optimal dose regimen.

with the compelling profile of 06. We've observed to date.

For continuing to engage with the ATD community, key opinion leaders, and advancing our discussions with regulators.

We're excited to announce the day that the FDA granted our request for a meeting, which is planned for the end of this summer.

During this, we intend to discuss a potential accelerated approval pathway for 06 and a ATV.

Feedback from this meeting will help inform our potential registration study design and our plans to efficiently, Advanced 06 for easy individuals with alpha 1 who are in urgent need of new treatment options.

Building on our success with 06.

We are advancing our second RNA editing clinical candidate, WVE-008, for homozygous PNPLA3 I148M liver disease.

Similar to 06 and 07 our approach to 08 is deeply grounded in genetics.

The pnpla3 variant is a well-established driver of Nash and liver diseases. More generally yet there are no approved medicines that directly address this biology

There are an estimated 9 million homozygous pnpla3, i1 48m carriers across the US and Europe, or at a 9f higher risk of dying from their liver disease, compared to non-carriers.

Currently, the only treatment options are non-precision medicines aimed at reducing liver steatosis and early fibrosis, with limited efficacy for these I148M carriers.

Silencing pnpla3 can only partially address disease biology.

It's likely to leave residual pathology since it knocks down all pnpla3 protein without restoring. Healthy wild type protein which has important physiological functions in the liver.

As a result silencing partially addresses, the etosys, but inflammation and fibrosis, remain unaddressed or worse.

Recent clinical trials of pnpla3 silencing support this notion, as dose dependent increases in liver, enzymes were observed.

By contrast with 08, we aim to correct the i1. 48 M variant using our leading RNA editing capability.

Which is expected to restore PN P3 activity and lipid mobilization. Reversing statis and fibrosis and improving Liver Health.

In may we shared pre-clinical data supporting our Approach. At easel the European Association for the study of the liver Congress.

We demonstrated that our pnpla3 aimers delivered substantial editing of the i1 48 amp transcript exceeding. The 50% threshold expected to lower risk for liver disease.

Achieved concentrations in the liver expected to support substantial editing and decreased lipid. Droplet density more than SI RNA.

In our upcoming first-in-human study of 08, we plan to leverage previously genotyped populations to efficiently identify homozygous I148M carriers and accelerate enrollment.

We will evaluate target engagement with circulating biomarkers and assess early signs of efficacy using non-invasive imaging.

You remain on track for a CTA submission in 2026.

With that, I'll turn the call over to Kyle to provide an update on our financials Kyle. Thanks Chris, our revenue is the second quarter of 2026 was 2.3 million compared to 8.7 million in the prior year. Quarter and relates to our ongoing collaboration agreement GSK

Research and development. Expenses were 51.3 million in the second quarter of 2026. As we did 43.5 million in the same period in 2025.

The increase particularly reflects, and primarily reflects, continued investment in advancing our clinical programs.

Including preparation for the phase. 2A portion of in light and continued progress. On our RNA editing pipeline,

Our DNA expenses are 24.8 million for the second quarter of 2026 as compared to 18 million dollars of Prior year quarter.

The increased primarily reflects costs associated with supporting our expanding Pipeline and preparing for the next stages of development.

order with 490.6 million in cash cash, equivalents and marketable securities, which we expect to be fished Bond operations since 3320

While we expect to receive Milestone payments from GSK in the second half of 2026, it's important to note the potential future Milestones of the payments to us. Under our collaboration are not included in our cash Runway.

I'll now turn the call back over to Paul to closing remarks.

Thank you, Kyle. As we look to the second half of 2026, we believe we are well positioned to unlock value across our pipeline.

With 007, our Phase 2a trial in individuals with obesity is underway, and we are rapidly working to advance increasing combination and post-ingredient maintenance studies later this year.

With 00006, we are on track to meet with regulators on a pathway to accelerated approval. We are also working to bring our second RNA editing candidate into clinical development for PNPLA3 liver disease in the second half of this year.

Before turning the questions, I want to thank our team for the progress we've made and for their continued commitment to reimagining what's possible for patients.

I'll now turn the call over to the for the Operator, Operator.

We will now move into our Q&A session for those of you who are joining us via the Q&A webcast. If you would like to ask a question at this time, please raise your hand by clicking the hand icon at the bottom of your window. We would like to ask all analysts to please limit yourselves to one question per person.

Once called upon, please unmute your audio to ask a question.

We'll take our first question from Jung Jong with wedbush. Please unmute your line, and ask your question.

Hi uh, good morning. Thank you very much for the question. And um so the question is on uh the O7 program for obesity. And uh I want to confirm that for the ongoing phase 2A portion. The goal is to confirm that you are able to achieve 5% weight loss as compared to Placebo at 12 months to support the um advancement for this program into the indication of obesity and uh then um on competition therapy. Uh I believe other programs have reported or will report data and uh given the same mechanism, what would be your expectation on Pro Data from your own program? Do you think you will potentially be able to show any differentiation? Thank you very much.

Thank you. Um, I'll start with the second question, then we'll work backwards to the first question, because I think the answer to the second question is—

we do believe that, you know, I think it's it's valuable to see what others have been generating in that space, not just for the potential for increasing fat loss in. And remember these other data sets that people have seen in combination, wearing phase, 2A, High BMI, High, visceral, fat, High total fat, patient populations, and they were able to see as you point out. Substantial reductions in both fat, astral fat in particular, um,

And liver fat. We should remind that the liver fat was was pretty substantial. I think, given that in comparison, both of them pre-clinical 80/50, where we're about 3 F more potent and in our pre-clinical data where we've seen increased potency. I think we would expect to see those data as affirming. And that we would continue to expect to see with greater more durable, knockdowns potentially better data. So I think it's a great to see that the field sees that in the combination setting.

Speaker #2: data there and where the human genetics outlied, I think maintenance is an incredibly interesting opportunity for us in differentiation. Getting back to your first question, which I think is critical for people to hear, the phase two A is designed as you point out to be able to elicit that regulatory and cross that regulatory threshold of 5%.

Speaker #2: I think as we've been pretty consistent with looking at other studies like believe with the MaggerMag where there was less fat loss in this healthy population than we saw, there actually those that medicine had a greater lean mass gain than what we have.

Speaker #2: If we think about that equation and put our medicine into this population, we would expect to see no different, we should see weight loss.

Speaker #2: I mean, MaggerMag had greater than 5% weight loss in that treatment setting. I think it's also important to point out that the phase two A design is more consequential than just looking at and hitting that target.

Speaker #2: Remember, we built into the study intentionally by looking at diabetics and non-diabetics, adding MRI PDFF, the opportunity to expand this more broadly in cardiometabolic disease beyond just the obesity threshold in terms of looking at the treatment of MASH where again, we look at the comparators in this population that ability to see substantial liver fat reduction is consequential in the field of MASH.

Speaker #2: And so we'd want to see that data we'd want to see the data on hemoglobin A1C and we'd also want to see the data on lipids.

Speaker #2: So I think in the totality of this is a cardiometabolic drug including obesity. I think this study is designed and poised to unlock that opportunity.

Speaker #3: We'll take our next question from Samantha Smenka with City. Please unmute your line and ask a question.

Speaker #5: Hi, this is Ben on for Sam. Thanks so much for taking the question. I guess maybe following up on the first question, in the phase two A in light trial, you know, what metrics are you focused on and what magnitude of improvement do you need to see to support, you know, specific expansion into MASH or type two diabetes or the other cardiometabolic diseases?

Speaker #5: Thanks.

Speaker #2: Thank you. And I'll let Chris talk about the endpoints that we're looking at and then confirm because we're going to talk about the what we're evaluating.

Speaker #5: Sure, sure. So we're looking at MRI PDFF, so looking at liver fat in the phase two A study. And so I know that there are other compounds in the same mechanism in the same area that have shown substantial decreases in liver fat, you know, that really are highly competitive with what's out there in the MASH space.

Speaker #5: And then we'll also be looking at hemoglobin A1C. We are looking at both non-diabetics and diabetics and we'll that's a measure that, you know, can change over a relatively short timeframe.

Speaker #5: And can be utilized as a registration endpoint. So we're excited to see what types of benefits we would have there. And then lastly, we'll be looking at a number of different the lipid profiles to understand, you know, if there's a potential there as well for, you know, to move forward into a lipid registration type study.

Speaker #5: Since there's very, you know, tight connections between lipid levels and cardiovascular outcomes.

Speaker #2: Just to add on, I mean, that's in connection additionally with the other measurements. So being able to look at both DEXA and MRI, which will give us that opportunity to assess visceral fat volume and total fat that's important because if we I know a lot of people want to always step back and kind of put these data sets of our phase one up against other phase two, three data sets and create tables and, you know, I appreciate the need for folks to do that.

Speaker #2: I think what is important is to remember in that low fat, low BMI, low visceral fat population, that even when we do compare that against comparator studies where people said, oh, your visceral fat reductions look relatively similar.

Speaker #2: Our visceral fat compartment was a liter versus five liters, almost five times as much visceral fat where we were seeing that reduction. So the ability that we've seen in this phase one otherwise healthy population is highly encouraging.

Speaker #2: And so we do want to be able to, for that comparator work, have MRI imaging to be able to set the comparators up where we have a high resolution imaging system to be able to do that.

Speaker #2: In addition, we'll look at other measurements like grip strength and others and be able to look at muscle retention because I do think when we do step back and think about this therapy in the context of particular care perspective and a patient perspective, yes, we want the cardiometabolic health benefit associated with is Eric pointed out is critically important.

Speaker #2: I think we oftentimes think about muscle strength. We can be able to assess that, but muscle is also a metabolic organ. And so the ability to look at that ability to retain and sustain muscle in the setting of that fat reduction are all endpoints we'll look at as well like waist circumference and total body weight.

Speaker #2: So again, there's a number of endpoints that we'll be assessing as part of this study broadly that encompass both obesity and cardiometabolic indications into value.

Speaker #3: Our next question comes from Steve Seathouse with Counterfeit Gerald. Please unmute your line and ask a question.

Speaker #5: Hi, thank you for the question. This is Nick for Steve. We just wanted to clarify in the FDA meeting end of summer, have you already received some feedback on an accelerated approval pathway and subsequently requested a meeting to discuss?

Speaker #5: Or do you not yet have any feedback yet? On a proposed accelerated pathway and this meeting in the end of summer will constitute the first feedback from the FDA.

Speaker #2: Thank you for the question. This would be the first meeting with the FDA. So when we submitted for the meeting, they granted that and this is when it's scheduled.

Speaker #2: So we would expect after that meeting to provide an update after we have written feedback. So we do appreciate the clarifying question that this is the first request for meeting.

Speaker #2: And we're excited that instead of a written response the FDA granted a face-to-face discussion on an accelerated approval pathway.

Speaker #3: Our next question comes from Jay Schwartz, the Leaving Partners. Please unmute your line and ask your question.

Speaker #5: Great, thanks for the update. I was wondering if you could give us some more insight into how enrollment is progressing in the higher BMI phase two A cohorts for 007 and what you're seeing in terms of screen failure rates and baseline characteristics.

Speaker #5: And when investors should expect the first meaningful data from these cohorts? Thanks.

Speaker #6: Yeah, so we're currently making really great progress on enrollment. You know, we're in the process of opening additional sites and, you know, once we have everything up and running well, we'll be able to comment more on kind of the timing.

Speaker #6: But so far it's been there's been really great interest in the study and it's enrolling extremely well.

Speaker #2: Yeah, just to, I mean, echo Chris' sentiment. Like momentum coming off the last data set tie both ex-US but also reportingly on this study US.

Speaker #2: So as we think about this study having actually the expansion we're excited to expand the number of sites and accelerate it. Also to Chris' point, remember this study has three-month time points and other assessments.

Speaker #2: We'll continue to look at it the rate of enrollment to guide while the potential is there for 2026, we have to see how we're progressing in the study.

Speaker #2: Ultimately to provide that guidance.

Speaker #3: Our next question comes from Whitney Egen with Clinical Genuity. Please unmute your line and ask your question.

Speaker #7: Hey guys, this is Angela on for Whitney. Thank you for taking your question. So maybe just another one on 007. Looking at the human genetic data, inhibin E loss of function does demonstrate the improved fat distribution as you've discussed, but not necessarily correlated with BMI as we understand it.

Speaker #7: So guess like what gives you confidence that we'll be able to see BMI improvement with monotherapy in the phase two A?

Speaker #2: Yeah, I think the correlation and it's interesting and I'll move back and forth with Eric on this one, but I think what is interesting is when we go back, there was a poster that we shared and actually on Lilam has done the work on a large I think it was for 300 patients as kind of a natural history cohort and non-diabetics.

Speaker #2: And actually showed active in E if we think about the actual ligand itself. Actually had strong correlation with BMI, insulin sensitivity, and truncal fat.

Speaker #2: So the data and correlation between the ligand and BMI is well correlated. I think the challenge in trying to and I think you bring up a very good point on the assessment of why BMI in itself is not a great indicator of body composition is, you know, you could be a bodybuilder and have higher BMI.

Speaker #2: So I think the context of really thinking about the addition of comorbidities where you get higher subcutaneous fat, higher visceral fat in addition to that becomes an important criteria and characteristic as we think about improvements in body composition.

Speaker #2: But I think what's encouraging is again, even in the setting in the phase one otherwise healthy patients, we did see substantial reductions in subcutaneous fat, visceral fat, so 3.3% reduction of waist circumference.

Speaker #2: And so I do think the ability to see those changes even in the lower BMI setting sets us up for encouraging changes and move to high BMI.

Speaker #2: But again, with comorbidity, those patients when you look at their characteristics and disposition are also high subcu fat, high visceral fat and obviously that's mechanistically what we've seen in reduction in the animal models.

Speaker #2: Eric, I don't know if there's anything or if you want to just add additional comments to that.

Speaker #5: Yeah, I think it covered most of it, but maybe just add a few things. So the phenotype and the genetic studies were adjusted for BMI.

Speaker #5: So just to design when we set that up now 20 years ago, those type of phenotypes that look at body composition, we wanted to adjust out like an overall body size.

Speaker #5: So just by design, it won't be associated with BMI. That's the first thing. The second thing is that human genetic carriers, they have 50% reduction and we think we need to get to kind of over 70% based on what we see in our animal data where we definitely do see total weight loss.

Speaker #5: And then I guess the last thing is that we already see total body fat reduction with one single dose at the 240 milligram cohort.

Speaker #5: So we're pretty confident about that now as we're rolling into higher BMI with much more excess fat to lose and multiple doses that we will get to the real weight loss as well.

Speaker #5: Just based on the total fat loss that we'll accumulate.

Speaker #3: Our next question comes from Salem Sayeed with Mizuho. Please unmute your line and ask your question.

Speaker #4: Hey guys, thanks for all the color today. Paul, maybe just one from us on the DMD side. Could you just provide a little bit more color exactly what caused the shift here to, I guess now evaluate potential partnerships in advance of filing the NDA for 531?

Speaker #4: And if you don't get the partnership, is there any scenario here where you still plan to file the NDA? Thanks so much.

Speaker #2: Yeah, thank you. I think we've been clear at the start of this year that we were going to seek a partnership for N531 and I think we remain consistent in discussions on partnering with N531.

Speaker #2: I think to the point of and the last part of the question of would we file absent the partner in advance, file in advance of a partnership, I think we're going to continue to evaluate the space.

Speaker #2: I think what's evolved in this space, particularly with the update that the existing PMO 53 Goladarson is going to file for a potential full approval early in the year and there'll be regulatory feedback around that.

Speaker #2: I think in advance of recognizing that you need to fully enroll or have well underway a confirmatory study in advance, wouldn't be prudent at this point in time until we understand that halfway.

Speaker #2: And continue to have the discussions that are ongoing around potential partnerships and collaboration. So I think we've just evaluated all of that relative to where the current funds are invested and that this decision we make.

Speaker #3: Our next question comes from Alex Ronahan with Bank of America. Please unmute your line and ask the question.

Speaker #4: Hey guys, thanks for taking our questions. Maybe one for Paul. Curious if, you know, after regaining the rights to 006, whether the pace or the nature of the FDA interactions have changed within AATB?

Speaker #4: And I guess looking ahead to the meeting this summer, is your expectation kind of in line with endpoints and study size based on recent precedence or any sort of unique aspects of your data set that could warrant saying even smaller study for example?

Speaker #4: Thank you.

Speaker #2: No, thank you for the question. And I think the short answer to your first part of your question is yes. You know, obviously by regaining the rights means that we can control the pace of regulatory interactions and with that could obviously accelerate them.

Speaker #2: And so that's obviously wonderful. I think to the second point, we wouldn't expect differences in terms of biomarker driven approaches for potential pathway, but I think it's again incumbent upon us and which is why we want to have a face-to-face meeting to get alignment not just on that biomarker driven pathway to potentially accelerate approval, but as you point out, just because others have requirements in terms of duration of study and numbers of patients, may not be equivalent for us.

Speaker #2: If we're doing a repeat administration, we may not have to run as long a period of time. And one of the other natures of the conversation that we're interested in is being able to open and explore what the full approval pathway looks like and how we might be able to more efficiently design a study that could have an interim analysis for the biomarker driven accelerated approval with the potential to sustain those patients on for full approval.

Speaker #2: So we expedite the time and pathway to get there. So all of this will be the nature of the discussions with the agency and we're excited to have that.

Speaker #3: Our next question comes from Madison Al-Saadi with B. Reilly. Please unmute your line and ask your question.

Speaker #6: Hey, guys, good morning and thank you for taking our question. So what MRI PFF liver fat reduction would the team consider a meaningful cross read to match?

Speaker #6: Is this something we would benchmark against resdifra which I think was around 30% relative reduction? Or is there a population difference we should be aware of?

Speaker #6: And then maybe if you could just touch on your fall investor day. If this is something that's really anchored by 006 regulatory update, obesity progress, or is this really more about the broader earlier stage platform?

Speaker #6: Thanks.

Speaker #2: Thanks Madison. I think at a high level, I mean, look, as you point out, we've already seen from others in the field in a high BMI, high fat setting that they could achieve 44% reduction.

Speaker #2: So greater than existing therapies and products that are approved and match. So I think the potential is out there. I think with signals, I think we're going to look for similar signals.

Speaker #2: And potentially the opportunity for more robust signals if we have a more potent drug, but also the ability to have a therapy to achieve that, which could potentially be as a reminder, you know, we have still the potential for once a year dosing.

Speaker #2: So as we think about the opportunity in this field for once or twice a year dosing to be able to achieve that alongside beyond just the treatment of liver fat, all of the other potential cardiometabolic benefits that come with inhibiting silencing, we think there's a tremendous opportunity in it as a differentiated product for the treatment of MASH, but we need to generate that data.

Speaker #2: And I think it's important as Chris outlined that the current phase two A study beyond obesity is designed to elicit these signals so that we can look at the data evaluate that and evaluate a potential path forward.

Speaker #2: As it relates to our fall research day or investor day, as it's evolved too, that's pretty consistent. I think you all have attendees, we've done these now for nearly a decade.

Speaker #2: And so we try to do that consistent piece of understanding what's coming. I mean, if you think about the history over the last couple of years, it was inhibiting, introduction, and then path to clinic, last year, PMPLA3, path to clinic.

Speaker #2: So I think there's an opportunity to learn about future programs I think as we talked about bispecifics and important field that we're opening up and so the opportunity continues to see more there.

Speaker #2: We'll always guide if that's the best place, where data is coming or where updates are coming. As you also know historically, if there's a meaningful update, we'll provide that absent having an event to hold that for.

Speaker #2: So again, it's always been an opportunity for us to share. Whether that's data pre-clinically or clinically, we have that opportunity coming up. And we'll share more on what's going to be that schedule in the very near future.

Speaker #3: Our next question comes from Kathryn Novak with Jones Trading. Please unmute your line and ask your question.

Speaker #7: Hi, Lauren, thanks for taking my question. I just wanted to drill down on expectations for monotherapy body weight loss for 007 in patients with type two diabetes.

Speaker #7: You know, we've seen combination data with incretins showing inhibiting knockdown might help sensitize patients to therapy, but you know, what do you exactly expect to see with monotherapy in type two diabetes relative to what you've seen in healthy overweight patients?

Speaker #7: Thanks.

Speaker #2: Yeah, no, thank you for the question because I think early on there were a lot of discussions that I think confounded this field into diabetics, non-diabetics, and that that would be different around thinking about combinations.

Speaker #2: And I think it's important as we think about how we bifurcated it. And again, as we shared on the prior question, the work that's encouraging is that there doesn't appear to be for inhibiting and BMI and insulin sensitivity and truncal fat that observational study that was run was in non-diabetics.

Speaker #2: So this correlation is not tied to a diabetic sub-cohort of population it's the whole population that would be amenable to that. So when we step back and look at it, we're not going to miss an opportunity if there's a signal either in one versus the other, we'll have both.

Speaker #2: The real opportunity we have in bifurcating and studying the diabetic population is because we have hemoglobin A1C, we'll be able to look at what's seen in human genetics of the ability of inhibiting or activating reduction to actually improve insulin sensitivity and improve hemoglobin A1C levels potentially.

Speaker #2: So we'll be able to see that signal. But the study design, as we said, is designed to capture body weight reduction in a total in a patient population that has higher BMI, higher sub-Q fat, higher visceral fat, look for those cardiometabolic improvements more broadly.

Speaker #2: But again, not tied specifically to a sub-population. And I think that was kind of a red herring, like a year ago that I know spiraled into this being a diabetic sub-population for effect, but actually the data in human genetics and in the population studies that have been run don't demonstrate that to be an effect.

Speaker #2: But we'll have the study to elicit that.

Speaker #3: Our next question comes from Ben Bennett with Wells Fargo. Please unmute your line and ask your question.

Speaker #8: Great, thanks so much. I wanted to ask about the 008 program as this is now moving towards the clinic, the PMPLA3 liver disease program.

Speaker #8: I think you've mentioned that a 50% editing you would expect to see sort of a positive clinical effect. How did you arrive at that threshold?

Speaker #8: And is that the threshold that you might expect in patients?

Speaker #2: Sure, do you want to speak to the genetics and the driver?

Speaker #8: Yeah, thanks for the question. So this is anchored on the human genetics observations where it's known that individuals that are homozygous for this variant, they have a nine times higher risk of dying from liver disease during follow-up versus the heterozygous that are just mildly increased risk.

Speaker #8: And so the risk reduction if you go from homozygous state to heterozygous state is more than 80%. So that's kind of what drives this 50% as the bar that we want to try to achieve.

Speaker #8: That getting higher than 50% is also better, but at the 50% we would expect to have the therapeutic effect. So that's kind of at the center of what and yeah.

Speaker #2: And then just to follow on to that because I think, you know, as we spend more time on this, this program, because I do think it's an exciting one, you know, I think the confounding data too that's coming out on the siRNA silencing of that enzyme is equivalently important, right?

Speaker #2: So we're talking about now fixing it and repairing it and bringing it up to 50%. I think the human experiments that have shown that decreasing that continually actually leads to potential worsening in liver disease.

Speaker #2: And we have to think about this not just in the fat accumulation, but in the inflammatory aspect and fibrotic aspect, which is actually this particular enzyme works on both where the fat's located and on that anti-inflammatory, anti-fibrotic effect.

Speaker #2: And so I think on both sides the data continues on human genetics, why 50%, but also why silencing it is potentially detrimental.

Speaker #3: Next question comes from Chacha Yang with Jeffries. Please unmute your line and ask your question.

Speaker #7: Hi, this is Chacha on for Roger. Thanks for taking our question. Thanks for the updates here. Mostly just a question on timing for your phase two.

Speaker #7: Can you just let us know what we can expect for your data releases? Are you still going to be doing updates for three months, six months, nine months, et cetera?

Speaker #7: And then just a sense on timing for that. Thanks.

Speaker #2: Thanks. As we've said, previously, the studies initiating recruitments going extraordinarily well, dosings moving, until once we have a cadence for when we can expect so we don't have to provide multiple updates on guidance, we'll have a good sense of patients and timing and we'll provide that updated guidance as soon as we have a sense of the enrollment.

Speaker #2: I don't know, Chris, does anyone want to add to that?

Speaker #5: Oh, yes, I think you covered it. We're just, you know, bringing on some new sites and just trying to accelerate it as much as possible.

Speaker #5: And there's a lot of interest. And so once that's kind of at a steady state, we'll be able to provide, you know, guidance.

Speaker #3: Our next question comes from Danielle Green with Trust Securities. Please unmute your line and ask your question.

Speaker #8: Hey guys, this is Alex on Virginia. Thanks for the question. Question on AATD. I know it's a little bit early to talking about the potential commercial question, but as we think about the opportunity any initial market research or anecdotes about physician or patient preference for a mechanism that is not a gene therapy, whether that's hesitation or awareness of off-target permanent editing potential of gene therapeutics, just curious what your current temperature checks are from patients and clinicians.

Speaker #8: Thanks so much.

Speaker #2: Thank you, Alex. And yes, I mean, we're doing our market research analysis obviously in preparation for feedback from the agency on potential pathways to accelerate approval.

Speaker #2: And they include not just as you outlined patients and clinicians, but also payers. And I think is we're engaging around this, I think we're seeing a lot of support across all three constituencies.

Speaker #2: To your point, hesitancy on permanent genetic mutations with the potential for editing cancer-associated genes and what that risk factor looks like to be discharged over time.

Speaker #2: The risk that maybe you might not be able to get be amenable to other editing therapies if you were to come on, not to mention as you point out, the potential safety of risk.

Speaker #2: So as we're seeing that, we're seeing a lot of support for RNA medicines and not dissimilar to other therapeutic spaces like TTR, where people are seeing if you can get through a redosable durable, so, you know, pushing yeah, potential monthly dosing or less frequent, that ability to see that play out with correction.

Speaker #2: We're seeing a lot of support for that. And as we think about the payer conversations, I think the idea that you need like over a decade of safe durability to break even on an RNA medicine, we're seeing a lot of support on that side.

Speaker #2: So again, as we're testing the constituencies, we're continuing to see a lot of support for RNA medicine approach to AATD.

Speaker #3: Our next question comes from Ananda Ghosh with HC Wainwright & Co. Please unmute your line and ask your question.

Speaker #5: Hi, thanks guys. Paul, continuing on the diabetic question, you know, historically the impact of incretins on the body weight in T2D patients has been always lower compared to pure obese patients.

Speaker #5: So given the differentiated MOA of incretins, what are your thoughts? Like what do you think, you know, the 007 might have an impact on in the diabetic patients' differential?

Speaker #5: And then I have two follow-up questions.

Speaker #2: Yeah, Eric, I'll let you start and then I'll join.

Speaker #8: Yeah, so I think that's a great question. It's actually kind of at the center of why we think it's important to look at diabetics and non-diabetics separately because we know that weight loss mechanisms are different.

Speaker #8: Mechanistically for mechanism like this, there is directly driving weight loss through fat loss. We do think it has a lot of potential for diabetics, but to Paul's point, we also know based on both human genetics and observational studies that this is effect is also important in non-diabetics.

Speaker #8: So that's why when a study both in the phase two A trial.

Speaker #2: I don't know anything to add to that.

Speaker #3: Our next question comes from Cassie Yuan with RBC Capital Markets. Please unmute your line and ask your question.

Speaker #4: Great, good morning. I thank so much for taking our question. It's grieving me. Hi Paul and maybe Chris on your PNPL3 program. You've elaborated how RNA editing of I148M variant is expected to be superior to saRNA silencing, but meanwhile Madrigal recently licensed an saRNA you didn't mention preclinical data showing AMR reduced lipid accumulation more effectively than saRNA and given evidence that PNPL3 silencing may also lead residual pathology in inflammation of fibrosis.

Speaker #4: So just curious how you would articulate the potential clinical differentiation of 082 patients and potential partners and how you're thinking about patient enrichment and selection for the first in human study.

Speaker #4: Thanks so much.

Speaker #2: No, thank you. And you know, one, I think there's a lot to unpack there. And I think on one hand, as you point out, it is a commonly detected mutation.

Speaker #2: So when we think about the ability for PNPL3, it's in consumer genetic tests. So it's into we had a patient here, even just a week ago, kind of discussing the disease from one of the liver foundations.

Speaker #2: And she found out she had PNPL3 liver disease through one of her consumer genetic tests. Like that and her kind of charting the diagnosis, she knew she had liver disease, was getting evaluated and, you know, I think the drive to actually drive genetic testing there is increasing.

Speaker #2: So I think that's encouraging and there's work that we're doing obviously in preparation for the clinic about enriching and identifying these patients in advance.

Speaker #2: So again, work that can be done that Chris in the development team are doing to enhance the enrollment and speed with which we can generate human data sets.

Speaker #2: I think to your point, the growing body of evidence both in preclinical and clinical data on silencing versus editing is continuing to accumulate. As we shared at the last our professor day last year, where we provided some of the preclinical data is, yeah, we see that there's this shift in terms of silencing where we can do SI so we can knock it out if we wanted to.

Speaker #2: Editing was much more efficient in terms of driving not just fat reduction, but also improvements in other inflammatory biomarkers. And I think that the more we can end up sharing there, as we think ahead.

Speaker #2: I think what's encouraging as well as we think about this distinction is recent presentations of usual on saRNA therapies that did show dose dependence worsening in the liver disease.

Speaker #2: So I think the clinical data is continuing to accumulate on what happens if you knock out that important enzyme and the data is continuing to obviously amass preclinically and with us going into the clinic and being first, we'll demonstrate human data the ability to show that by restoring the function of this enzyme is the human genetic suggests, we should be able to make efficiently not just a treatment for what happens with fat, but the reason this enzyme may be at the center of so many different liver diseases beyond just MASH is a function of its impact on this reactive oxygen synthesis system, kind of this pro-inflammatory system.

Speaker #2: And it's been seen time and time again that if you can increase this, you can improve the fibrotic side. I don't know, Eric, if there's anything to add on the preclinical data and Chris on the kind of way Eric, if there's anything to add on the preclinical.

Speaker #8: No, I think you were very comprehensive. It's the bottom line is that, you know, you want to restore it to a function it has an important wild type function.

Speaker #8: So if you knock it out, you can accelerate some aspects of the disease and that's really where we by using an RNA editing approach, we're restoring it back to normal.

Speaker #2: Okay.

Speaker #3: Our last question comes from Mara Goldstein with ClearStreet. Please unmute your line and ask your question.

Speaker #4: Great. Thanks so much for taking my question. I know it's late in the call, but I'm just curious if you can provide some color as you're thinking about sort of the cardiometabolic signals that you're looking for for 007 in the trial.

Speaker #4: Sort of how do you weight that and or rank order what you'd be looking at and what the threshold might be?

Speaker #2: Thanks for the question. I'll step back from rank ordering. I think they're all important as we think about cardiometabolic diseases. They're all different, right?

Speaker #2: As we've elucidated, like the ability and I think this all stems as Eric shared during the remarks earlier visceral fat drives when we think about what's so important ultimately in this disease process is visceral fat as you go by 10% to that difference, that increase in visceral fat, just 5 to 10% drives a whole bunch of different cardiometabolic output.

Speaker #2: So this ability to see that substantial reduction in the output of that becomes important as we think improvement, as we said, we've already seen, you know, 14% reduction, 15% reduction in visceral fat.

Speaker #2: So we're consequentially changing that now in an otherwise healthy population. And again, being able to evaluate that in the Q8 population is interesting for us, right?

Speaker #2: Because it's going to allow us to look at each of these markers, you know, what happens with hemoglobin A1C as a function not just in stratifying patients, diabetic non, but really the impact on hemoglobin A1C, which by itself is a marker for registration and type 2 diabetes.

Speaker #2: What's happening with lipid levels and improvement in lipid levels is seen in the human genetics, but also potentially for insulin sensitivity as we think about HDL, triglyceride ratios.

Speaker #2: And then the ability to look at that in its compendium of obviously fat loss and weight loss and at least the more general. So I think, and MASH with liver fat.

Speaker #2: So I think we're looking at all of these independently and in their global association with each other in the context of obesity and cardiometabolic disease.

Speaker #2: I don't know, Chris or Eric, if there's anything to add to that.

Speaker #3: Well, I would just say,

Speaker #8: you know, we'll look at the data and see where we're best differentiated and where we can move forward the fastest and, you know, you can think about MASH, for example, where you can get an accelerated approval.

Speaker #8: That could be attractive if we're seeing strong effects on lipids there. In the liver, so that's sort of how we're looking at it. Just following the data and taking the best things forward into the most accelerated paths we can to get things approved.

Speaker #2: Eric, anything to add?

Speaker #8: No, I think you covered it. I think they're all, I guess the only thing I would add is that it's all comes back to the mechanism as in driving fat loss and decreasing visceral fat and that mechanism is really linked to all of these outcomes.

Speaker #8: So there are a lot of opportunities here.

Speaker #2: Great.

Speaker #3: Thank you. There are no further questions at this time. I'll now hand the call back over to Paul Bolno for closing remarks.

Speaker #2: Thank you for joining our call this morning. We appreciate your continued support. Have a great day.