Wave Life Sciences Ltd. ($WVE)

Welcome.

Thanks, Rob.

Welcome to the inaugural session of the 47th Annual Goldman Sachs Healthcare Research Conference. Pleased to be joined by Wave Life Sciences, and Paul.

So first, Paul, for those in audience and listening, who may be less familiar with Wave today specifically, what do you think is the most important thing for investors to understand about the company and where it stands today?

Well, thanks for having us. And it's a great time to be connecting as we kind of hit the midpoint of 2026. We're kind of at, what I would call, a strategic inflection point on operating against what we set out as a strategy as we began 2026, which is: one, we see our platform chemistry translating into potentially meaningful therapies, starting with WVE-007 for Inhibin E coming off of our initial clinical data seeing again in the siRNA space, our chemistry uniquely translate to a meaningful improvement in body composition in a Phase I healthy volunteer study and excited for the updates as we transition to the Phase IIa high BMI study, which should be starting shortly, so we'll spend more time, I'm sure, talking about that, but that's obviously a very critical component in our evolution. Second is the growth of our RNA editing platform, which is exciting, led by alpha-1 antitrypsin deficiency and the work we have there. And this summer being a key inflection as we engage with regulators and a potential pathway to accelerated approval, being able to differentiate that program in the RNA editing field from other therapies for alpha-1 antitrypsin deficiency and critically unlocking the platform capability for RNA editing, where we'll have WVE-008, the first RNA editing program for PNPLA3, so a disease of 9 million patients, that will come into the clinic as we end this year. So again, lots of progress across siRNA, RNA editing. And we're excited to continue to do the work on the platform, and we're well resourced to execute on those clinical trials.

That's great. We'll get into individual programs here in a sec, but maybe before doing so, investors often debate the value of a platform in breadth versus depth. You obviously have a few different RNA modalities. How do you think about the benefit of having RNAi or any editing, splicing and emerging by functional modalities all under one roof?

Yes. I think when we step back and say -- I think there's lots of different ways to define platform companies, right? You can become a platform company off of biology. When you build a platform company off of chemistry, the main value there is to really demonstrate that, that capability is translatable. And so when we think about building an RNA medicines company, the goal and the premise has always been how do you unlock the power of emerging clinical genetics, right? How can you find? Because I do think, for our field and our industry, the biggest challenge is how do you find high-value, high-impact targets to make medicines for patients. The value of a chemistry platform is how do you unlock those genetics so that when those interesting, compelling, high-impact, high-value targets become accessible that you can be poised to translate those innovations. So case in point, Inhibin E going after a validated genetic target in the UK Biobank for obesity and cardiometabolic disease is intriguing on the RNAi side and we'll talk about our differentiation on chemistry where we're seeing that not just translate preclinically, but now in the clinic given our unique and proprietary chemistry. Equally important, as we think about alpha-1 antitrypsin deficiency, PNPLA3-driven mutations for disease and liver, these are all opportunities not on the silencing side, but where actually -- and we'll talk about PNPLA3 specifically given some of the presentations at EASL that are reaffirming that siRNA is not the approach to take down the mutation, but correction is to be poised to have a platform that can correct an enzyme, lets us jump on that opportunity for those 9 million patients and have a potential therapy. So I think the key on the platform is really how do you drive differentiation. I'll step back and say, when we talk about Inhibin E, I think the uniqueness of, again, the work that the team has done in that is special, and we'll see that later R&D Day this year as we talk more about, to your point, this bifunctional capability, which is how do we interplay these modalities of either dual silencing targets or silencing and upregulation editing in one molecule.

That's great. Maybe now turning to 007, before getting into study design data, can you talk more broadly about biological rationale of Inhibin E as a target in cardiometabolic, and maybe also what you've learned about it over the course of the last little bit?

Yes. I mean, one of the very important points as we said is, we like targets where there is human clinical validation for those entrants so that when we're working on a program that there is clinical support that if you interrogate that target with a medicine that you have a higher probability of that medicine translating in the clinic for patients. Inhibin E is a wonderful example of that. It's kind of like the PCSK9 for obesity in the sense that the UK Biobank data set has shown that there is very good translation of this target. People walking around with a 50% loss of function of this target have low abdominal visceral obesity. They have more lean mass. They have lower lipid levels, so lower triglyceride levels, higher HDL levels. And most importantly, the human outcome study has been run. They have a low risk of cardiovascular disease and a lower risk of type 2 diabetes. So if we think about the totality of the evidence that says this is an important medicine for cardiometabolic disease, including obesity, the clinical genetics tell us that. I think stepping back and saying the translation from human clinical genetics to a medicine often entails the pathway of not having to be born with it, which is a great maintenance study, but ultimately, how do you create a therapeutic. And so this was our opportunity to really start to say, can we answer a fundamental question on our platform capability, opening up an opportunity unique to Wave, meaning can we take advantage of a target that the body has just a little bit of more biology of the target is a target that's the ligand is produced in the liver and hepatocytes and uniquely targets a receptor on adipocytes, ALK-7, and we can talk more because there's always a lot of conversations around ALK-7, but the unique mechanism is actually the ligand communicating with that receptor. So the target is the ligand. What it does is it actually kind of puts the brake on lipolysis. So evolution was always about fat storage when calories were not plenty, and so therefore, the desire was how do you build and store fat. When you take the breakoff lipolysis, you see that breaking down, oftentimes starting with highly vascularized fat like visceral fat and then proceeding into the subcutaneous compartment, and we'll talk more about the ability of this in both subcutaneous and visceral fat. So the key when you're developing a therapy is always will this translate? Can we uniquely translate this? And so far, we've been unique in the sense that our chemistry has translated to the only single dose reduction in body weight in the I/O animal model so we could give a single injection of drug. We could see weight loss comparable to the GLP-1s all driven off of fat, so preserving lean mass. And I think that's important as we talk, not just about the importance of muscle as a stabilizer, a functional component of muscle, but muscle is an insulin sensitizing organ. So as we talk about cardiometabolics, this idea of fat reduction, lean mass preservation then ultimately translate into healthier outcomes. So we demonstrated that in the mouse model monotherapy can show monotherapy reduction in fat leading to weight loss. We did a combination study, and we know with the evolution, and we'll talk more about that clinically, but the idea that you could get even more weight loss when you combine these with GLP-1s with that weight loss coming off of just fat. So it gives you the opportunity to think about how do you preserve muscle sparing in the context of incretins. And the last, which we think is a very compelling opportunity that we've demonstrated preclinically is maintenance. And as I said, that's also the compelling opportunity that's been seen in the UK Biobank clinical genetics, which is that if you knock the target out prior to cessation of incretins, you prevent rebound weight gain even in the setting of higher caloric consumption. So this idea that if you want to transition from incretins onto a muscle preservation, but not lose or drive that weight regain, and remember, that weight regain that patients experience where the body weight comes back usually 2 or above where they started is driven off of fat. So these patients, from a health standpoint, actually accrete more fat after they stop than they had at the beginning of the study. So the ability to think about this is a therapy where you can give a once to twice a year injection that sustains patients. And I think when we think about these 3 use cases, it's a prime opportunity that we've been able to see that chemistry platform that you were referring to uniquely translate to Wave in seeing that. And we've seen these data both in the preclinical studies now translate to humans, where a single dose in a Phase I healthy volunteer study we could recapitulate that biology with a substantial reduction of visceral fat, about 15%, reduction in subcutaneous fat, about over 5.4%, and most importantly, a reduction in waist circumference of 3.3%, which is tightening of belt loop. When we think about that in the healthy setting, which is a very different setting than people historically look at obesity studies, that data was, in our minds, very compelling in the translation of moving into obesity studies that look like other larger obesity studies.

Makes sense. Maybe on -- you mentioned a little bit about this, but the unique chemistry platform that you have, this is a target that many others, including some of the largest names in RNA, have tried and frankly, haven't even been able to get a molecule into the clinic let alone continue through clinical development. Maybe just briefly in terms of what allowed you to bring something potentially very compelling to the clinic.

Absolutely. I mean getting back to that concept of platform chemistry, and it's -- we appreciate the question because oftentimes, as portfolios mature, we spend more time saying, what's unique about the clinical data and driving the clinical opportunities in it, forgetting that probably one of the most fundamental criteria of Wave is an oligonucleotide chemistry company. And I would say Inhibin E is giving us the opportunity to truly say that we have the potential of best-in-class in siRNA in this category is Wave's unique chemistry, meaning with the phosphoryl guanidine and our stereochemistry and control, the ability that -- and we published this paper probably about 3.5 years ago in NAR, we were able to compare it to, as you pointed out, some of the best oligonucleotides that are translating in the clinic and do head-to-head comparisons where we could see improvements in potency and improvements in durability. I think at the time where we were generating that work in the target space, a lot of the targets we're kind of exploring of what more would you gain? You could gain more in terms of decreasing dosing frequency. And those are all -- I'm not discounting that, those are important and interesting. But it was really when we saw Inhibin E where we said, here's a target that is under pressure, to your point, is eluding others because it needs that suppression. This would be a wonderful target actually to translate those chemistry innovations into strong differentiation in the clinic. And so this is a target that needs to be suppressed. And so again, to your point, the ability to suppress that target didn't just translate into preclinical animal obese models, but translated well even in the healthy volunteer studies and recapitulating that fat reduction, lean muscle sparing and durability to the point where, again, in this space, it's competitive now where we can have a once to twice a year subcutaneous injection that can drive really meaningful improvements in body composition.

Yes. Makes sense. Maybe on the data you've generated to date, obviously, reduction in lean mass, stabilization, there's a lot of focus on overall body weight. Like how do you interpret the data that you've had today, and maybe a little bit more detail than you've given as well as what do you think it means moving forward for the molecule?

Yes, I think when we step back and really say, what does it mean? What does it mean in obesity treatment? I think we are seeing an evolution. We actually just came to this conference from our time at ADA. And I think in the meetings there and in the settings before it, I think there's a real fundamental shift in how we talk about therapies for obesity. So we have had this compelling discussion about what does healthy weight loss mean? It means improving body composition. It means sustaining lean muscle mass, which does weigh more than fat, and shifting the narrative to pounds on a scale to what does improvement in body composition look like overall in terms of improving human health. And so when we think about that, and I'm often reminded -- many people have heard this, but I just think it's the right way to visualize this. One of the key opinion leaders in this space, I'll give her credit, Angela Fitch, she has a very great analogy in her clinics where patients who come in, they may weigh 250 or more pounds and they come in and they say, I want to lose weight. I want to be 170 pounds. She is like, why? What is it about? And I think it's because, for a long time, that's the only way we had to measure what's happening to our bodies, right? You stand on a scale and you watch the weights on pounds go down. And remember, those pounds are often driven by lean muscle mass loss. And we saw that when we analyzed the BELIEVE data on the incretin comparator arm, in 3 months, 50% of that reduction was lean mass loss. So that's the tool people have to see that. And so when these patients come in and say, I want to be 170 and she'll hold up a picture of Michael Phelps and say, if I told you, you're going to be over 200 pounds, but this is what you were going to look like, would you want that? They go yes. And I think it really changes the narrative visually of what people are really looking for and how important that lean muscle mass preservation is ultimately to human health. So we moved the conversation past pounds on a scale driven off of weight loss and really reframed the discussion to what does healthy weight loss look like? It is substantial. It means you need to lose substantial amounts of fat to drive that body composition. And I think -- hands down, I think the tools for that are getting better and more distributed. I mean we're seeing scales now that people have in their homes that cost as much as body weight scales that actually enable people to measure their body composition. And it will be really interesting in the evolution of some of the incretins as people watch on that scale and see not the weight go down, but the lean mass changes that correspond to that, I think it will allow us to kind of reframe and refocus the narrative on what's important, which is fat reduction. So to your point, coming into that framing, recognizing that the clinical trial that we delivered first was healthy volunteers. So I think it is important we oftentimes use BMI, and coming out of ADA, I can say BMI is uniformly viewed as not an ideal way to be talking about this space because you can be a bodybuilder with a high BMI or you could be obese with -- an unhealthy with high BMI. And so it is important to think about not just high BMI, but our study excluded patients with comorbidities. And it's the comorbidities that drive increase in fat, visceral fat and subcu fat. And that is what you ultimately want to see. So in the Phase I, even in these healthy patients, we saw substantial reductions in visceral fat, 15%, just to put that in context because I think we always talk about numbers. An increase in 5% to 7% in visceral fat drives a number of diseases. So we can talk about cardiovascular disease risk, risk of diabetes. And as you kind of cross up to that like near 10%, you're talking about MASH. And so if we think about that change and seeing a 15% reduction in visceral fat in a healthy population, that is a really consequential shift for human health. We also saw, and I think it's important when we get beyond what drives health outcomes is the reduction in subcutaneous fat and recognizing that, that's what drives change in body weight. That's the larger compartment. We saw a shift in declining subcutaneous fat by 5.4%, and again, in these patients who did not have a substantial amount of fat to lose. And that translated -- I always say, what does that translate to as we think about what's meaningful to patients is that 3.3% reduction in waist circumference, meaning this was translating. Additionally and very important in the obesity therapeutics landscape is, this came with a safety profile that was extraordinarily clean. So for these medicines, the only AEs were mild irritations at the injection site in some patients without dose dependency. So again, the important piece is safe and driving these meaningful changes in body composition. And again, reinforcing for us, I mean, the lowest dose, 7.5 months after that injection, we were still suppressing Activin E. So the notion that you've got durability and then frequency, safety, but most importantly, those improvement in body composition in this Phase I population, I think is incredible as we kind of make that transition to the Phase II high BMI patients with comorbidities, with and without diabetes, where the setting is more fat and will look more similar to other trials that have been run in this space, and I think we're poised there to see meaningful differentiation.

Yes. Maybe along those lines, and as you're going into that patient population, any expectations for what you're going to further learn about the program in terms of dose optimization, et cetera., as well as kind of key differences in overall study design versus your Phase I?

Yes. So I mean first is very different in terms of Phase I. So this shift is a shift in the population. So this will be high BMI patients with comorbidities with and without diabetes. And as we model what that delivers and with all the waist circumference parameters that other studies have, that sets up the population where we would expect substantially increased levels of visceral fat and substantially a level -- increased levels of subcutaneous fat. And we've put it in baseline characteristics with other obesity trials. This study does have MRI and MRI-PDFF, and we'll talk shortly about liver fat reduction. But by having MRI in the study does give us a way to ascertain a baseline, whether or not we're meeting the body composition similarity. So again, the study will be poised to deliver that change. I think with and without diabetes is equally important. So what do we want to see in this study, we'll have 2 different doses that we'll be looking at, the 240 and the 400. So that will let us have the ability to discern how do we optimize that infrequency of administration in those settings. We'll be able to explore that on the PK side. But on the PD side, one of the opportunities we have, so if we think about endpoints in this study, beyond just obesity and weight loss. So we're obviously going to measure body weight reduction, body composition by DEXA and MRI, but we're going to have other endpoints in this study with which we can evaluate other opportunities given that obesity is a metabolic disease, but what are the other cardiometabolic diseases that are approached with this mechanism. So one, the reduction in fat, which we've seen from others who have developed their assets. We still think we have a threefold improvement in ED50, but it was highly encouraging to see in this setting post a number of about a 44% reduction in liver fat. I mean, that's substantial compared to other MASH drugs. So the ability to have that opportunity in the study to discern our own data set and what we can see is compelling as an end point. Two, hemoglobin A1c. So again, looking at the diabetic patients, let us evaluate what the impact would be on other biomarkers. Hemoglobin A1c is an endpoint that doesn't require an outcome study in diabetes. So we'll have that. And we'll also be able to look at lipid levels, which, again, the human genetics shows those improvements. So we'll be able to discern those endpoints in addition to things like insulin sensitivity looking at HDL triglyceride ratio. So I think in totality, this monotherapy study is really poised to unlock the potential for Inhibin E in obesity and other cardiometabolic diseases as a single agent, realizing that there's 30 million patients in the U.S. who are at risk of lean mass loss that need an approach to body composition improvement and fat loss and is uniquely poised to do that. I think the settings that will start beyond this, so there's 3 trials that will start on the heels of that, so this study will initiate this quarter, next study will be the combination study. So this will give us the opportunity to really look at directly with an incretin, and it's safe to say, given that others have looked at the combination with tirzepatide that, that would be a fair way to view this combination study. And the ability there is really not to drive weight maxing at the risk of lean mass, but ultimately, how do these 2 features intertwine. So the ability potentially is something like the low clinical dose of tirzepatide to see that you can maximize fat loss without having to push the incretin from a tolerability perspective and a lean mass loss perspective. And if we think about the idea that 70% of patients are intolerable to their incretin beyond a year, how do we think about these as keeping patients on meaningful medicines and maximizing body composition improvements. The third opportunity, which we're excited about is maintenance, and that's recapitulating exactly what we did in the animal model and showing that we could dose Inhibin E prior to cessation of the incretin and be able to have a way to sustain that weight reduction that patients have achieved, but do so without continuing the incretin to suppress lean mass, again, tolerability and have, I think, a unique way to drive adherence, which is we speak to. Payers is something that everybody is focused on is the investment to get to a certain body composition, and what's the risk to staying there? We know patients, they're investing financially and trying to stay there. And so the ability to work with patients on maintenance to be able to have an off-ramp to incretins is pretty exciting.

Great. Maybe just briefly, you talked liver fat reduction, obviously, looking at in T2D, but potential outside of just obesity [indiscernible] of broader cardiometabolic opportunities?

[indiscernible] broader metabolic opportunities, in particular, as you mentioned, diabetes, MASH, what was formerly called PCOS and going through evolution, there's lots of ways to think about metabolically driven diseases that are driven off of importantly, visceral fat. And so the opportunity where we have a potent reduction of visceral fat drives a whole host of cardiometabolic inflammatory diseases. And so again, a unique approach where we're doing that, where the biomarkers are part of the study. And I can't emphasize that enough that when one runs studies in obesity, people kind of have in their mind the classic body composition, DEXA and weight. And I think the ability that we haven't missed the opportunity as part of the study to embed these other biomarkers and tools of measurement are going to give us that opportunity to unlock that potential as part of the study that's initiating. So that will continue to generate data over time in a number of indications that we can unlock.

Great. Turning to 006, several different approaches for AATD. I guess, maybe briefly before getting the data and what you've seen to date, why do you think RNA editing is a compelling approach here? And maybe also briefly on your RNA editing platform?

Yes. So I mean, RNA editing in general, we think, is an interesting platform. It's compelling in that we don't have to work at the DNA level with permanent mutation. So the ability to have a way to either correct a transcript or upregulate a transcript opens up the potential to explore a number of therapeutic opportunities. AATD is the unique one in the context of correction, meaning you've got a single mutation on the transcript that if you can correct you can restore the production meaningfully of healthy wild-type protein. Focusing on the ZZ patients, which is where we do, these patients make no N proteins. So it gives you [indiscernible] to evaluate how your medicine works, whether it's [indiscernible] one. And first and foremost is reducing the Z protein, right? These patients may have 2 copies of Z protein, and that's what's produced. That protein gets stuck in the liver, it's also secreted, but it's the toxic folding of that protein, which damages the liver, and therefore, by reducing that toxic protein, you ultimately enable liver repair. And I say this because as we talk about editing versus other approaches, protein replacement therapy, we have to remember that alpha-1 antitrypsin patients are both lung and liver patients. So these patients have both higher risk of liver disease as well as lung disease. When we think about lung disease, and we'll talk about this shortly, it is a chronic disease of acute exacerbation. So what happens are, we all have kind of steady-state levels because it's an acute reactive protein that sit in the background. What really happens when we're exposed to an irritant is that UC or pneumonia, cold, kidney stone, that the body increases IL-6 and CRP, that's the acute inflammatory response. That increases the transcripts that produce the protein, the protein then gets produced to protect damage from occurring. And it's that chronic damage that happens over those acute exacerbations that injures tissues. So the approach that editing has actually is to recapitulate changing these patients. So if we think about patients on the spectrum of ZZ to SC to MZ to healthy MM, as these patients have less Z and the ability to produce more M, they are protected in their various tissues. So that's exactly what we saw preclinically, and that's exactly what we saw in the clinic is that as we treated with 006, we saw, and it was actually really beautiful when you think about the curves that all patients were responding and you could look at an individualized patient level and actually see that their Z protein substantially reduced and they end up producing more M protein. And we expect that, as the liver continues to get better, those can continue to increase to higher levels. What's nice is we can recapitulate getting to that MZ like phenotype, meaning reduction of Z, production of M, and importantly, having that acute phase response. So for example, we did see that when patients had an acute phase response, they could produce total protein levels greater than 20 micromolar. And so this idea that you could generate that protection when you need it is really the fundamental aspect of what editing is supposed to do, do that safely in a way that you could redose it. And as we know from clinicians and patients, reverse it, that if you stop the medicine, you haven't permanently altered the DNA of those patients. I think it's important because sitting on the other side, as you asked the question on replacement, there is the replacement concept, which is really focused on just the lung. So that's infusing a protein in the background setting [ still ] of a ZZ patients to try to be there to protect that tissue. The challenge there is, these patients, when they have those events, it's consumptive proteins. So that protein goes away. So I guess the best way to think about these 2 as we do in either end of the pendulum is one is depleting the protein during the event, the other is producing the protein into the event, which we think is a core advantage of editing in general. And it's nice to see other editors also demonstrating those same features and phenomena. So I think that's a core component of editing. We think about DNA editing versus RNA editing, again, I do emphasize that the idea in liver patients to not have to use LNPs that can be pro-inflammatory in liver is an advantage. And we saw that as clinicians reporting patients with more advanced liver disease, F1s, F2s on the studies as the study progressed is important. And as I said, not being able to off-target edit. That's not about bystander editing. There's a whole concept still around creating the M protein versus bystander M protein, which is kind of thinking about that as an on-target, off-target, but then there's also the risk of permanent off-target editing that's irreversible, and that's a very real risk. And so as we think about this balance having a reversible approach in RNA editing, we think, is highly compelling.

Great. Over the course of RestorAATion-1 and 2, what have you learned about PK/PD profile of the molecule and how it informs kind of go-forward plan here?

Yes. I think as we know and said in the last trial, the 200 biweekly was looking at that dosing versus 400 monthly. And so it did give us the potential for, as we said, monthly dosing in this. I think what we'll continue to look for is whether or not there are opportunities on that dosing regimen. And if you look at the curves at the end of these studies, we do see duration. So as it's loaded on to cells and as we're continuing to see that activity, the potential for less frequent administration or other dosing regimens is in the evaluation. I think the key for us right now is staying focused on this potential for monthly dosing and whether or not -- where that sits in, generate those data and continue to evaluate it.

Great. You mentioned 008 earlier. What initially drew you to PNPLA3 as a target? And why do you think RNA editing is the right approach here?

Yes. So PNPLA3 mutation, this is -- as we said, we like targets that have validation. So it's got very strong genetics on the mutation of this enzyme drives an increase of disease. There's also very good genetic epidemiology data that shows that if you can correct it back to 50%, you improve the survival of some of these patients, so their risk of volatile liver disease goes down. So very strong genetics in shifting these patients from the homozygous state to the heterozygous state. The question is, and there's been a number of RNAi approaches, we demonstrated this work. We shared it in an R&D Day in the past that if you take this enzyme away, you can actually increase the risk of disease in these patients, meaning you could see increases in potential for liver fat, you could see increases in inflammatory response that aren't addressed, and that's really the ability of correcting the enzymes so they can do its' function, expel fat, improve the inflammatory response. So when we did our own comparisons between these 2, and I think we're pretty good at making siRNAs given what we did with Inhibin E, we could really do that kind of cross comparison and modality to say, well, what's the right modality to treat this? I think recently and coming off of EASL very shortly ago, I think what we're continuing to see is that the siRNAs are doing that. They are actually, as they're dose-dependent, potentially worsening of the disease. So really shifting and reaffirming, frankly, from the human clinical data on the RNAi front, that correction is the right way to pursue this. And so we're excited to bring that data from our preclinical data that shows that potential now to the clinic where we can address this. And it is a very consequential size. And it's all for liver disease, while we're starting and looking at things like MASH and others are doing that, there's a whole variety of diseases that these patients are exposed to. And oftentimes, it goes undiagnosed in the context that these patients go on to have liver diseases for other consequences, whether it's alcoholic cirrhosis and hepatitis to other liver diseases from infection that they just have an exacerbated response. And this is an identifiable mutation, it's in 23andMe. So this is not an exotic mutation to look for and evaluate.

Great. Maybe in our final minute, what do you think is the most underappreciated aspect of Wave today?

Yes. I think when we go back, within each of these diseases we're talking about, there is that desire to see the next step. So I think what's underappreciated is how important body composition is ultimately to the obesity landscape, and we're -- how we believe we're best poised to address that with Inhibin E both with our existing human data, again, remembering that the underappreciated fact is that was a Phase I study and delivered results that very meaningfully should translate into the Phase IIa, and we're going to do that. We're resourced to deliver that IIa study and the subsequent combo and maintenance. Additionally, AATD is an asset. We'll deliver those data and then with the upcoming regulatory discussions for that pathway and continue with PNPLA3 to unlock a very broad indication in the editing space. So I think collectively, we're resourced to deliver a portfolio that's translating across platforms, across mechanisms to deliver high-impact, high-value diseases.

Great. Well, that concludes our time today. Thank you, Paul. Thank you for coming. Great to have you.

Thank you very much. We appreciate it. Thanks.