Hey, welcome everyone. It's one of the final sessions of the Cantor Fitzgerald Muscular Dystrophy Symposium days, but ending on a good one. We have Christine Siu from BridgeBio to talk about the limb-girdle muscular dystrophy program, which gets very little attention. Sorry, I've got something going on in my background here. There we go, sorry. I had something in my ear that was squawking away. Yeah, so a program that doesn't get the attention it deserves, I think, just in part because it's not one of the leading late-stage assets, but it's pretty darn close and pretty darn interesting. So, great to have Christine join us to share a little bit about this program and hopefully educate some investors on the BridgeBio approach to limb-girdle muscular dystrophy. So let's dig in.
Christine, maybe just give us a quick overview of LGMD and really what differentiates the different subtypes of the disease.
Yeah, sure. So of course limb-girdle is a disease that's characterized by the progressive loss of, of muscle function. It's caused by mutations, at least with LGMD2I, it's caused by mutations in fukutin-related protein. And, based on mutations, there's different severities of the disease. So with LGMD2I, about 70% of the patients are homozygous for the L276I mutation. They, typically are diagnosed in their late teens to early 20s. They experience, loss of daily tasks of living along the way, such as trouble walking, trouble going upstairs, you know, trouble standing up from a sit position. They'll ultimately be wheelchair-dependent. Sometime in their 40s, they'll experience respiratory decline, as well as cardiac dysfunction. In about 30% of patients, we kind of put them into the other genotype bucket. They experience a more severely progressive, form of the disease. They're typically diagnosed in late childhood.
They're mostly wheelchair-dependent in their 20s. They will also experience respiratory decline and have higher rates of cardiac dysfunction. There are no approved therapies today for the limb-girdle.
What’s the difference between LGMD2I and R9, because I guess they get grouped together?
Yeah, it's, they're the same. It's a nomenclature issue. So basically, historically, it was termed LGMD2I, and then somewhere along the line, they decided to rename all of them with R9. So they're the same thing.
Okay, very helpful. Yeah. And so they're pathologic variants of the fukutin-related protein, if I pronounce that correctly. What is the fukutin-related protein? What does it do?
Yeah, so FKRP, as we kind of call it for short, basically glycosylates alpha-dystroglycan. And glycosylated alpha-dystroglycan acts as a shock absorber between the muscle fibers and the extracellular matrix. And so when alpha-dystroglycan is hypoglycosylated, as it is in this disease, the muscle fibers basically deteriorate over time with just kind of chronic daily use. So our therapeutic strategy is effectively a substrate replacement strategy where we're giving supraphysiological doses of the substrate to drive the residual enzyme activity, thereby increasing the levels of glycosylated alpha-dystroglycan.
Okay. Now, just again, still on the high-level questions for LGMD 2I, is it a genetic diagnosis primarily, or can one look at a patient's phenotype and presentation and have a high degree of suspicion that it's LGMD2I specifically as opposed to one of the other forms of LGMD?
It's confirmed genetically now.
Okay. And is there typically a high index of suspicion that it is specifically LGMD2I, or does it just kind of get diagnosed as LGMD, and then the genetic testing gives the MD the specific etiology?
Yeah, it's the latter. It kind of goes into the general bucket, and then the specific diagnosis is confirmed with genetic testing.
Got it. So if FKRP is responsible for glycosylation of alpha-dystroglycan?
Yeah, you can just say αDG. That's like ADG. It's a lot easier.
Yeah, there are so many dystrophins and glycans, etc. So presumably there, there's kind of a dose effect that patients with more glycosylated A DG do better than patients with less amounts?
Yes, that is generally the principle. I think you can look at maybe a couple different sources of information, right, for this. I think, one, first of all, we know that you need at least 50% of glycosylated αDG to have basically normal function. I mean, people who only have one mutation, it's a homozygous disease, so people with only one mutation are effectively asymptomatic. And then you can look at the genotype-phenotype relationship in the mutations in FKRP. So patients who are homozygous for the L276I mutation, they typically have about, you know, 10%-20% normal levels of glycosylated αDG. And they have a progressive severe disease, but it's more slowly progressive than the other genotype mutations. Those patients typically have about 5% of normal glycosylated αDG, and their disease presents earlier and more quickly progresses.
Okay. So, does that then imply if the mutation is in the FKRP enzyme?
FKRP.
FKRP enzyme, that there is some residual activity of the enzyme. It's just not functioning nearly at the capacity it needs to be?
That's correct. Yes, you need residual enzymatic activity for life. We don't know of any, like, nulls, basically, that exist. And you also need residual enzymatic activity for this therapeutic strategy.
Got it. Let's introduce the substrate, I guess, of FKRP is ribitol, and maybe help us understand the biology here, what FKRP's effect is on ribitol and how that leads to glycosylation and αDG.
Yeah. So ribitol is one of the substrates of FKRP. It basically uses the ribitol to glycosylate the alpha-dystroglycan. And so what we're doing basically is, you know, just giving, you know, in layman's term, a whopping dose of ribitol to drive the residual enzymatic activity to increase glycosylated αDG.
Where does this concept come from that you could essentially, like, ramp up the activity of the enzyme by drowning it in more substrate?
Yeah, that's a good question. I mean, really a lot of this data was generated in the labs of Dr. Lu, who's kind of one of the scientific founders here. You know, he published a paper in which he demonstrated that if you could give excess levels of ribitol to diseased mice models, that it elevated their levels of glycosylated alpha-dystroglycan, and that led to functional improvements in both the skeletal and cardiac muscle of these mice.
What is the normal source of ribitol? Does it come in our diet, and how much are we getting, and should we be getting more ribitol?
So it's not generally consumed in the diet. It's just naturally produced by the body. And I, you know, think based on some of the work we've seen early on, it there does seem to be a threshold level at which if you're just kind of taking just extra physiological doses of ribitol, it doesn't really do much beyond a certain level. So I'm not sure that a normal person would benefit from just taking a lot more of it. But I think in a disease model where, you know, you're obviously, you know, a mutation in the enzyme is causing kind of less benefit of the sub of the end product, we're basically just trying to, you know, catalytically drive the whole process.
Got it. So, which cells normally produce ribitol? Is it made in the muscle cells themselves, or outside the muscle cells and transported it?
I believe it's made inside the muscle cells, and then it's transported to the extracellular matrix. And it basically binds the extracellular matrix to the muscle fiber. And that's how it acts as the natural shock absorber, if you will. The amount of the glycosylation, the glycosylated, you know, chains are basically acting as a shock absorber between the muscle fiber and the matrix to prevent its continuous, you know, deterioration with just the friction of daily use of the muscle.
So, the dose of ribitol that you're delivering is rather high. It's 12 grams twice a day. Maybe help us understand the absorption, the transport kinetics for how it actually does get into the muscle cells that you would need as high a dose. And how did you ultimately land on 12 grams twice a day as the target dose?
Yeah, it is a high dose. It's predicated on the theory that kind of more is better from a standpoint of trying to elevate glycosylated αDG. We did some early dose-ranging studies, both in healthy volunteers as well as patients. What we found is, you know, we could go up to basically 12 grams twice a day with, you know, a very well-tolerated side effect profile. None of the patients have basically, you know, discontinued therapy because of the side effects. Although, you know, what you would expect, of course, from someone taking such a whopping dose is you do have, you know, mild GI disturbances, right? You're going to get some bloating, right? Some maybe some nausea, maybe some GI effects.
Got it. An important theme over the last couple of days has been biomarkers, reliability of biomarkers. Why don't we talk about ADG as a biomarker? You've noted fairly clearly that, you know, patients who have 5% of normal ADG do quite poorly. If you can get that up to 10%-20% of normal, they have a much, much better prognosis. How do you measure ADG? And talk to us a little bit about the development of that biomarker in muscles that you're using.
Yeah, yeah. So, so we've developed a novel assay to measure glycosylated alpha-dystroglycan in biopsy tissue from, from patients. It is a fluorescent Western blot, and it is highly sensitive, reliable, and has a much greater dynamic range than some of the other methodologies that we've explored to measure glycosylated alpha-dystroglycan. We have had the opportunity to actually discuss with the FDA the use of the assay to measure glycosylated alpha-dystroglycan. And, you know, so far those conversations have gone quite well. They're comfortable with the assay, with the validation, and with the data that we've generated using it, at least with the natural history study and demographics.
Are there any other biomarkers to consider beyond the muscle ADG levels that might be relevant or predictive?
Yeah, definitely. I mean, we're certainly measuring creatine kinase as well. I mean, that's a general marker, general marker of muscle deterioration, but I think it's still useful, especially, you know, if you can demonstrate magnitudes of decline in it, supportive of what we're also seeing with alpha-dystroglycan. And then some of the other markers we're following in our studies are going to be markers of cardiac decline, right? I mean, it's, it's muscle, and these, these patients do experience some cardiac dysfunction. And so, troponins, for example, might be an example of something that we would look at because they're certainly a very well-established marker of cardiac muscle function.
Maybe you can talk a little bit about the heterogeneity of αDG levels with, you know, certainly between patients. It's going to be high. What about within patients? Is there much noise in this assay and, you know, have you been able to measure that? Are there serial biopsies of untreated patients that give you a sense of the noise level of that assay?
Yeah. So basically, the bottom line is we haven't seen much noise in the assay and much noise in the measurement of measuring alpha-dystroglycan with patients. We have looked at serial biopsies of both healthy volunteers as well as patients from the phase two study. So we haven't seen that. And the way we are measuring the glycosylated alpha-dystroglycan in the studies is we are basically cross-referencing it to a control range as well.
Now, are all patients included in the program? I guess to your point, you haven't found patients with no FKRP activity. So in theory, any patient with residual FKRP activity could be a candidate for therapy. Is that right?
That's correct.
Okay. Are there patients who you would expect to have a better response based on their baseline or residual FKRP activity or other factors? Who would be kind of the ideal candidate to have a good response?
That's a good question. I'm not sure that we could define it that way in terms of predicting right clinical response based on patient subtype. Certainly in the clinical study, just based on what we have to measure from a functional endpoint perspective, we're only evaluating ambulatory patients for the functional endpoint. I mean, we're treating all comers, but only using ambulatory patients, you know, as evaluable for the primary endpoint. But that's more from a clinical trial perspective, not necessarily, you know, kind of how patients do per se, right? Like better or worse on the drug.
Got it. Again, before we get to kind of an overview of the data that you've shown, you know, it's just as we think conceptually, you know, another theme throughout these couple of days is hearing about patients having meaningful functional improvements, but then also trying to correlate that with whether it makes sense. What I mean by that is, you know, in myotonic dystrophy, you know, if you're really improving the dystonia of a patient, which can actually get much better, you could also envision improvements in strength, et cetera. In Duchenne's muscular dystrophy, where you're treating a severe phenotype and converting it into a, you know, a less progressive disease, it's surprising to hear patients doing much better when really all you'd expect is for them to deteriorate just more slowly.
So, you know, as we think about the biology here, a priori before clinical data, is this an approach that you would expect would improve patients' function, or is it an approach that you would expect would stabilize or just slow the degree of progression in patients?
Yeah, that's a loaded question. I mean, of course, the holy grail would be to improve patients' functions. But I, you know, obviously from a clinical trial perspective, I don't think that's what we can expect. We are, you know, really hoping to slow the progression of the disease and, you know, at best, right, arrest the decline.
Helpful. All right. Why don't we talk about some of the data that you've shown? We can start with the biomarkers and then move on to the correlation with some of the clinical observations you've seen.
Yeah, sure. So you want me to discuss the what we've seen from the Phase 2 study? Is that?
Yeah, that. Yeah, please.
Yeah. So the Phase 2 study was an open-label study in 14 LGMD2I patients. And what we saw were improvements in the biomarkers at three months that was durable over the course of the study out to 21 months. And we also saw some hints of kind of functional improvements as well in the study. So from a biomarker perspective, of course, we looked at glycosylated alpha-dystroglycan in the homozygous L276I patients. Glycosylated alpha-dystroglycan doubled from approximately 16% at baseline to 40%. For the other genotype buckets, the alpha-dystroglycan nearly doubled from 6% to about 10%. Oh, sorry. Did you, do you want me to continue?
Yeah, maybe just kind of on that point, going for well, first of all, for the homozygous patients, the baseline you said was around 15%. Is there a wide range of, you know, where that baseline would be across the broader population, or would you expect most patients to kind of be in that, say, 10%-15% range?
You know, I think the range we've seen is probably like 10%-20% at, you know, at most. That comes from our natural history study as well as what we saw in the Phase 2 study. You know, I think the numbers that I'm quoting—I think the lights just went off in the conference room. The numbers that I'm quoting were basically the medians from, you know, those 14 patients.
Got it. Going from 15% to, say, 40% would, in theory, portend a fairly dramatic improvement if the homozygous, heterozygous patients are normal, you're bumping up to normal levels of αDG. Is that kind of fair that, you know, that kind of a signal would indeed portend a fairly strong clinical effect?
Yeah, we're pretty encouraged by that. So I think what we also saw, right, from the heterozygous, right, in terms of going from 6%-10% was also encouraging. I think we're encouraged by that for a couple different reasons. I think, one, there's the genotype-phenotype relationship, as you suggested. So if we're taking the, you know, the kind of other genotypes who are more severe to a level of alpha-dystroglycan that is basically the baseline levels of the less severe patients, right, you can kind of think about it as we're making the more severe patients look more like the less severe patients, right, if the genotype-phenotype relationship holds. So I think that gives us encouragement. I think the other piece of data that gives us encouragement is also from what we've seen in the preclinical studies.
So in the mouse models, they showed a similar elevation of alpha-dystroglycan that also led to functional improvement in skeletal and cardiac muscle tissue. And so I think that's the other piece of this where, you know, we're pretty hopeful about the benefit, right? The functional and clinical benefit that could be derived from this.
Got it. And so for the L276I homozygous patients, again, the baseline was around 15% and a really dramatic improvement. For the other genotype patients, they're starting much lower but are around 6% or so at baseline, moving up to 10%. What, why is there this difference in baseline and arguably to some extent responsiveness between the L276I and the other FKRP genotypes?
Yeah. Well, so, so first of all, I think there is a genotype-phenotype relationship in the amount of glycosylated alpha-dystroglycan they start with. So that kind of goes back to the fact that the more severe patients start out with lower levels of glycosylated alpha-dystroglycan. In terms of the different response, right, between the two groups, I'm not sure that we know why that would be the case. But I mean, we are, you know, stratifying the results, right, based on the genotype.
And in terms of the improvements that you're seeing in αDG levels, is there, again, a wide range of improvements? Do you see, like, hyperresponders and non-responders, or do you generally see most patients kind of moving up to a somewhat similar extent?
There's obviously some variability, but I mean, across the board, we saw, you know, the overwhelming vast majority of patients improve across on alpha-dystroglycan. So it was I mean, I think, you know, there's maybe one patient that didn't show an elevation in glycosylated alpha-dystroglycan. But other than that, you know, the, the data were pretty consistent.
Now let's discuss some of the clinical observations that you're finding because they really do seem to correlate with the biomarker and appear to have some dramatic improvements.
Yeah. Well, I guess the other biomarker I would just mention too from the phase two study was the marked decrease in creatine kinase that we saw.
Thank you.
Right. That was so, you know, that was a 75% reduction in CK. I know that CK often gets, you know, the criticism of CK is that there are wide daily fluctuations in CK just from, you know, daily muscle use. But I don't think that could account solely for the magnitude of the drop we saw in CK. So that's the other data point that kind of gives us comfort that, you know, what we're seeing on the biomarkers could lead to improvement. And then, you know, kind of going back to what we saw with the functional improvements, everything has to be caveat with the fact that this was an open-label study in 14 patients.
But that being said, we did see what looked to be like a stabilization in functional measures, namely the 100-meter timed test, 10-meter walk test, and the North Star Assessment relative to what would be expected in the natural history of these patients.
Got it. I so appreciate the way BridgeBio thinks and operates because, right, to your point that, you know, it's an open-label study, so it can be oftentimes hard to interpret the clinical data. But you actually look to correlate the biomarker with the clinical improvement where, you know, if there's a placebo effect happening here, it's not a placebo effect that's going to be correlated to the ADG levels. Maybe explain what you saw there and what the meaningfulness may be.
Yeah, yeah. No, thanks for mentioning that. That's also kind of one of the key data points for us coming out of the Phase 2 study where, as you suggested, you know, we did show a correlation in the change from baseline in glycosylated αDG with the change in baseline for, primarily the 100-meter timed test. And so that does give us encouragement that, of course, if we're trying to use, you know, alpha-dystroglycan as a PD marker for efficacy as well as a target endpoint for accelerated approval, there is a reasonable, reasonable likelihood that it will predict clinical benefit.
Is there any reason to think that prolonged expression to very super-physiologic ribitol levels may somehow wind up downregulating enzyme activity or leading to loss of effect?
If there is that concern, I have not heard that in the general community yet. We haven't seen that, in the phase two patients. We've been treating them now out, you know, past 21 months, and we haven't seen that. We've seen a, you know, continued, a sustained increase elevation in our glycosylated αDG, a sustained decrease in their creatine kinase, which is, as you said, you know, all been correlated with kind of functional stabilization of functional measures. So we haven't seen like a rebound or potentiating effect that, you know, as you're kind of asking about.
I believe it's been around six months since the last data update from the program here, the phase two program. Should we be looking for any additional data updates as patients are followed longer?
I don't think so. I think the next data update for us will be the enrollment of the interim analysis for the Phase 3 study and then data from that.
Perfect, perfect segue to the FORTIFY trial design, and help us understand the, you know, that trial design and how it was informed by the phase 2 program.
Yeah, sure. So the Phase 3 study is a randomized placebo-controlled study in LGMD2I patients. There are effectively two parts to the study. The first part is an interim analysis looking at the biomarkers at 12 months in about 42 patients. And there we will be looking at the change from baseline in glycosylated alpha-dystroglycan. We'll be looking at the other biomarkers like CK and cardiac function and looking at, you know, some functional measures. And the strategy is really to pursue an accelerated approval using glycosylated alpha-dystroglycan as a surrogate endpoint with that data.
Why, why 12 months and not sooner given the fairly rapid increase that you see in αDG levels with therapy?
Yeah, really good question. So yeah, so what we saw, of course, from the Phase 2 is that the biomarkers moved pretty quickly. We saw the magnitude of change, at three months. And what we're trying to do with the, interim analysis at 12 months is to look at some clinical measures that may also move at 12 months to, to get at this idea of, is the change in baseline, in alpha-dystroglycan, at three months reasonably likely to predict clinical benefit at 12 months? And so that's why we chose the 12-month endpoint, because, you know, it's harder to see change in clinical measures at three months. And so we're going to look at FVC primarily, at 12 months.
Got it. And so, sorry, you might have said this. The final analysis is at what time point and what endpoints?
Yeah. So the full study is looking at the North Star assessment as the primary endpoint at 36 months in a larger cohort of patients. That'll be in about 81 patients. And, you know, the North Star assessment is the primary endpoint that the FDA strongly suggested we use for the study. But the North Star assessment is a relatively insensitive clinical measure. That's why it takes, you know, 36 months to power the study appropriately to show, you know, potential treatment benefit on it. And it's why kind of the strategy also lends itself to an accelerated approval strategy where, hey, right, like, we'll run the study to 36 months on North Star. That'll be the confirmatory study.
But given the biological plausibility of alpha-dystroglycan here, given the unmet need because there are no approved therapies for these patients, you know, kind of lends itself to an accelerated approval sooner rather than later, for these patients.
And maybe you can characterize the conversations with the FDA that may give you optimism that that interim analysis would serve as an accelerated approval basis. And you know, ultimately, like, as you get the data, what are you looking for to then kind of support that premise?
Right, right. Yeah. So we've had the opportunity. We've had, actually, multiple meetings with the FDA, on the subject, on this program and the subject of potential accelerated approval. They have been, you know, open and collaborative, that accelerated approval using glycosylated alpha-dystroglycan as a surrogate endpoint, you know, is a potential pathway. It will, of course, be a review issue and based on the data that we generate. But, you know, so far they have been open to, to, to that idea, given, you know, all given the biological plausibility, given, you know, the fact that it's directly in the targeting this disease at its source and the unmet need.
the data that we would be hoping to generate, right, to support that accelerated approval is very similar to the data that we showed in the phase two setting, but in a randomized control setting where we demonstrate, elevations in glycosylated alpha-dystroglycan. We demonstrate other improvements in biomarkers. So a totality of evidence type of argument, right, where we also show, reductions in CK and improvements in, potential improvements in cardiac markers, of function. And then looking at the clinical measures, kind of principally FVC, if we can correlate the change in alpha in glycosylated alpha-dystroglycan at three months to a change in any of the clinical measures at 12 months, that could also potentially kind of get to this question of, you know, is, is a change in glycosylated alpha-dystroglycan a surrogate endpoint? Is it reasonably likely to predict clinical benefit?
So how important then is it to see a correlation with FVC and/or the 100-meter time test to either continue the trial to completion and/or consider filing for accelerated approval?
Oh, good question. I think so it will ultimately depend on the data, of course. You know, if you were to ask me, you know, I would be pretty aggressive here in terms of pursuing an accelerated approval strategy based on the biomarker data alone, kind of what we've seen. And we've had some of that feedback actually from some kind of ex-FDA regulatory consultants as well that we've spoken with. But again, it's a totality of evidence argument. So I think the more data that we can generate that is supportive of this idea that improvements in glycosylated alpha-dystroglycan can lead to clinical benefit, I think, you know, it's obviously just a stronger data package.
Why did you go with FVC specifically as a key secondary endpoint when it didn't look like one of the key endpoints in the phase 2?
Yeah, yeah, good question. So, first of all, we did not measure it in the Phase 2 study because we did the Phase 2 study during COVID. And so, you know, that was, you know, a confounding factor there. We chose FVC for the interim analysis for a couple different reasons. One, we don't expect the North Star to change, you know, at 12 months, which is why we have the three month-long study. And so it doesn't make any sense to look at it at 12 months. And, you know, certainly it doesn't take away from our alpha as well for the primary endpoint. And we have seen data generated from other studies that shows that FVC moves more, you know, is more sensitive, I guess, to change in a 12-month period of time.
And so we were kind of hopeful that that would be, you know, more like more likely to demonstrate a therapeutic benefit at 12 months.
Okay, got it. I think, on this topic oh, I guess last question. So on, on this particular point of discussion, this feels like the mirror image of Duchenne's with instead of dystrophin, there's the α-DG biomarker. In many ways, the effect you're showing on the biomarker is arguably more pronounced than drugs that have been approved for, for Duchenne's. One thing that seems to have really helped Duchenne's drug development is the power and advocacy of the patient community. Very vocal, very powerful. Maybe you can characterize the voice and coordination of the LGMD community.
Yeah, yeah, it's a good it's a good question. Certainly the LGMD patient community is very active. We've certainly partnered with them as well to be a voice, as well to the FDA in helping to educate them about what's important from their perspective. They're very vocal about the fact that they're just very hopeful for anything that can arrest the daily loss of daily activities, right? That's what they focus on. Like, what else am I going to lose, right, as they go as their disease progresses? So from their perspective, there's a huge urgency to have something approved sooner rather than later and not necessarily wait for a 36-month trial. So we have partnered with the patient advocacy organizations, you know, pretty strongly. We had a patient advocate, the mother of a daughter living with this disease.
She came to one of our FDA meetings to discuss the use of alpha-dystroglycan as a surrogate endpoint and the potential for accelerated approval. I think, you know, her participation was quite compelling and educational, I think, for the FDA. The patient advocacy groups have also been organizing educational sessions, scientific forums, in D.C. that we have participated in as well, just to, you know, again, further education, right, to the regulatory agencies about what's important from their perspective. And certainly we've, you know, been careful designing those studies in mind with them as well to make sure that we're trying to incorporate what is important to them.
How many patients in the U.S. estimated to have the L276I homozygous versus other FKRP mutations?
There's about 7,000 patients in the U.S. and Europe, and about 70% of the patients have the homozygous L276I mutation.
Got it. And it, you know, it's such an interesting and novel and thoughtful approach to treating this disease. Is there any reason to think that one could apply a similar strategy to either other forms of muscular dystrophy or other enzyme deficiency disorders?
It's tempting. It's very tempting. I think, you know, this approach obviously is specific to mutations involving FKRP and kind of the glycosylation pathway for alpha-dystroglycan. So with this specific approach, I think the diseases it's going to be kind of relevant for could be, you know, the 2M and 2U forms. There's a Japanese mutation as well. These are kind of smaller patient populations, maybe in the order of another 2,000 addressable patients. But outside of those indications, I think it's something we'd have to, you know, give some thought to.
Excellent. Christine, thank you so much for the wonderful overview of a very exciting program, one that could probably stand on its own as a biotech company, but is in the BridgeBio portfolio of many other exciting programs. So it's great to have a little bit of time to dig in on this one. I'm very much looking forward to the interim update coming next year.
All right. Thank you. Thanks for the opportunity to share it.
All right. Thanks, everyone, for listening.