All right, perfect. Welcome, everyone. I'm Tiago Fauth. I'm a biotech analyst here at Wells Fargo, joined today by Pliant Therapeutics. Bernard Coulie and Éric Lefebvre joining us today. Thank you so much for making the time.
I appreciate it.
Thank you.
Great. So again, like, I know the platform story is a little broader, but there's most of the focus on IPF right now. So I thought we would just kick off with IPF historically, why failure rates have been so high? Like, you see a promising asset with some phase 2 data, then it doesn't translate. What are some of the shortcomings related to the indication itself? And then we'll go into how you guys came to address that over time.
Yeah, absolutely. I can start. You're right, IPF's been a really tough indication to treat. I mean, primary reason being, we don't really know what causes it. It's idiopathic. But we do know that it's driven the fibrosis, the collagen production in the lung is driven by TGF-beta. So people have tried in many ways to target TGF-beta over the years unsuccessfully. If you target it systemically, you get well-known toxicities that are pretty bad. But what we found is that by targeting two integrins, alpha V beta 6 and alpha V beta 1, that are upregulated in the lungs, in IPF and incidentally in the biliary tract in PSC, that you can target TGF-beta activation without affecting the systemic TGF-beta function. So that's what we've done.
I mean, the hard part about targeting the integrins has been selectivity and bioavailability. So we feel that we've solved that puzzle. The data that we've shown to date sort of bears that out. So we think we've got the solution here, that we can actually shut down the pathogenic TGF-beta activation that causes the collagen production.
Got it. And when thinking about just a broader potential for this molecule, when you're thinking about additional indications or how this may present, is it more about just tissue expression and tissue selectivity, or can you actually go broader now that you have... How broadly applicable is this across fibrotic diseases, I guess?
Yeah. Well, I think in the, in the lung, certainly, there are other indications with this similar pathogenesis of fibrosis. So we're talking about progressive pulmonary fibrosis, which is a label given to a number of different diseases that are... So rheumatoid arthritis, scleroderma, hypersensitivity pneumonitis, and some others, that result or can result in pulmonary fibrosis. Different diseases, different causes, but ultimately, TGF-beta is the common pathway that causes the fibrosis in the lung. So any sort of type of lung fibrosis that we've seen, we think we have a chance to treat with Bexotograst just because we can block that specific those receptors that activate the TGF-beta.
Got it. Oh, sorry, go ahead.
Yeah, I was gonna say, in addition to that, what's really been exciting for us to see over the past few years is that they've looked at IPF and ILD populations in terms of looking for biomarkers that are predictive of progression. And integrin beta six circulating levels have come out as some of the strongest predictors out of these publications. So that it really highlights the potential for Bexotograst to be used outside, not only in IPF, but other ILDs as well.
Got it. And again, we will talk a little bit more about that afterwards. So, relative to prior attempts of targeting TGF-beta, is it more about just pan TGF-beta and targeting versus your selective approach, and that kind of leads to the delta in safety and potential efficacy? How is this differentiated relative to what else have been attempted with the same mechanism of action?
Yeah. So TGF-beta has been targeted in many different indications. Oncology is one specifically that it continues to be attractive, but systemic approaches have proven toxic. So ALK5 inhibitors were one way that was tried, and there's a litany of problems that you run into: valve problems in the heart, skin lesions, a number of different things. And then nothing has ever really made it past like phase one, I believe. And so, you know, the interesting thing about alpha V beta 6, it's expressed on injured epithelial cells, but it's only expressed at very low levels in healthy tissue. So if you give Bexotograst to a healthy patient, you really don't see a lot of effect.
But that upregulation of alpha V beta 6 in the lung is what's activating that pathogenic TGF-beta. So by blocking that, we don't see those receptors anywhere else in the body, except just a couple of minor places. So we have no way of really affecting TGF-beta outside of that injured tissue.
Yeah.
So we think that's, you know, that was the theory going into the program. That was the purpose of the design of the drug that we developed, and so far, it's proven to be, you know, as tolerable and safe as we thought.
Yeah, and I know initially, that was kind of one of the key debates if you even have that slide with the preclinical summary put.
Right.
So far, any noteworthy clinical findings from a safety perspective?
No, I mean, this drug is. We've seen no dose relationship for adverse events. We've seen good tolerability, very few discontinuations. To this date, we haven't seen any drug-related serious adverse event. So it's really been really a good safety profile that we've been building upon. And we're going off to ERS. I'm personally going in later this week. But we have also a presentation on our integrated safety analysis that we did across all trials that continues to support the benefit of the favorable safety profile. And we have dosed over 700 study participants to date.
Yeah.
That's starting to be a meaningful-
And exposure out to-
Up to forty weeks-
Yeah
in the IPF and the PSC program. Yeah.
Got it, okay. Again, it's a fairly robust, like, safety database so far, right?
Yeah.
So, okay. So let's check that box and move to this efficacy discussion and some of your early findings in IPF. Yeah, can you just talk about the proof of concept? But again, I think most folks are interested in the impact on FVC, mechanistically, how that may play out, dose response. I have a couple of follow-ups there, but if you can just kind of summarize what you guys seen so far and how it stacks up versus standard of care.
Right. So our phase IIa was called INTEGRIS-IPF. It evaluated four doses, going from 40 to 320 milligrams, and then the 320 milligram dose cohort went to 24 weeks or longer.
Yeah.
Right? So it had the longest exposure, and this study was really primary endpoint with safety and tolerability. So that's something that we showed very clearly that the drug was well-tolerated, no dose relationship or adverse events. And I think the most meaningful adverse event we saw in that trial was, or the most frequent, was diarrhea, but most of it was in the context of-
Okay
... use with Ofev or nintedanib. So that was expected as well, and most of it was mild to moderate. Very few discontinuations. So that safety tolerability profile has been supported. In addition, we looked at efficacy through different measures, so FVC, the absolute change in FVC. We also looked at FVC percent predicted. So across all these different doses, we continued to see separation between active and placebo in the context of 80% of our patient population being on approved therapy. So that was meaningful in a way that we could, you know, really see that signal coming loud and strong. And we've looked at, for example, FVC percent predicted. There's a response category of 10% or greater decline.
Okay.
Clear dose response there. We also measured QLF, which is a measure of the extent of lung fibrosis. It's using CT scans. We saw very little progression at the two top doses, 160 and 320. Little or no progression over the 12-week period, and we also saw in the 320 milligram dose group that placebos continued to increase their fibrosis levels, but that was a very, very small increase, for example, compared. I mean, the 320 milligram group had a very small increase compared to those. So we really think that, in addition to some of the interesting cough data we saw.
Right
... so a statistically significant improvement in cough at 320-milligram dose supports the fact that we've shown good safety, anti-fibrotic properties, and effect on FVC and also on radiological measures of the disease. So really exciting from that perspective.
And again, like, I feel like this is a debate that has washed out for the most part, but given some emerging competitor data where you see an initial FVC benefit for an IPF drug, which we saw with your drug, and that later becomes a slower decline, which is kind of what you would have expect for most of the mechanism of action out there. So how should we think about that? Like, what is the target goal here, and how reliable is the signal of potential FVC benefit? Because, again, like, even the PET data shows that you are increasing fibrosis in a relatively short period of time, but is it reasonable to expect that to translate into an FVC improvement? Or, like,
I mean-
How do we scare off-
Yeah, we-
... start that off, yeah.
Yeah, we definitely have patients improving, right? I mean, we showed that-
Yeah
... in our INTEGRIS-IPF study, also in that Collagen PET study you mentioned. It's I think it's really what we're hoping for is really overall, in the study population, is more the concept of stabilization, right? If you think about the approved drugs, right now, they slow the decline by approximately half, the FVC decline by approximately half on a yearly basis. That's okay, but it's, you know, it can really be described as modest efficacy, and you also have the tolerability issues with the approved agents, right? So if we were able to further stabilize that FVC decline, and in fact, in our study, in the standard of care subgroup, which was the most meaningful subgroup, we showed an 80% reduction in decline over, like, on top of-
On top of
... existing therapies.
Yeah.
So that suggests that you were able to preserve lung function for a period of six months or more in these patients, and I think that would be meaningful. It's also important to understand that this target population, IPF, they're older individuals in their sixties, seventies, so it's unrealistic to expect a continued improvement, because increasing age will affect your FVC, as well. But certainly, we think there's a potential for stabilization, that would really be a big benefit for patients.
Got it. And mechanistically, just to go back to the PET data, because I was a little caught by surprise by that one, but can you just kind of summarize some of the key findings there? Because, again, like, it sounds like you've established a proof of evidence of benefiting fibrosis in a relatively short period of time, and I don't know if mechanistically that was something that you were expecting prospectively or not, but I'm curious how that kind of squares off the whole story.
For us, this was really exciting because not only... We had shown that there, from the INTEGRIS-IPF study, that there was less fibrosis measured by CT scan, but that's not collagen one, type one-
Yeah
... right? And that's where the collagen PET study was really quite exciting for us, but also for the PIs that are participating to INTEGRIS and BEACON. And the scientific community is that we were able to show decreased collagen deposition with over 12-week period for Bexotograst, that dose at 160 milligrams. So that's one of the two doses we're studying in BEACON. And we saw a continued increase in collagen deposition over 12 weeks for placebo, even though there were only 3 placebo patients. That was really beyond our expectations. This was the first interventional study that used this collagen PET, so there's not any other data like this to our awareness right now.
But certainly, it's really suggesting that this is true anti-fibrotic activity of Bexotograst, and that probably explains all the changes that we're seeing radiologically and also for FVC and symptomatically, potentially.
Got it. Okay. So I think it's fair to say, established that the mechanism is working the way that you intended to design. Safety profile so far has been good, so let's look forward a little bit. So BEACON, and just kind of recap, because you made a change to the trial, now it's an adaptive phase II, III, so it could be one of potentially two phase III trials at the end. So can you just kind of outline for us what's the current design?
Yeah. So right now, BEACON-IPF is being conducted as a seamless phase IIb/III trial, and what that means is under one master protocol, we have two independent studies. The phase IIb portion that will identify a phase III dose for continued development and the phase III portion. Each of these studies are identical, and same eligibility criteria, same endpoints, and so, and they're powered also to be pivotal studies. So they could serve these. Like, the BEACON-IPF could serve as the basis for registration in IPF because of there's two confirmatory studies in there. And why we upsized from 267 patients to 360 in the phase IIb portion is because we've seen higher standard deviations in the Galapagos phase III trial that read out a few years, so a year ago or so.
Yeah.
And what we wanted to account for that, because we wanted to increase the likelihood of phase IIb serving as a pivotal, right?
That's well consistent with United Therapeutics as well.
Mm-hmm.
I think they mentioned a similar reason why they upsized their own IPF trials, right?
Yeah.
Let's talk about just some of the key milestones here. You're going to get phase IIb data. It's going to be a fifty-two-week-
That's right
... endpoint, similar to everything else, so that will be your first card flip.
Mm-hmm.
So, what can you say in terms of progress, enrollment, operational challenges, like some of these IPF trials can take a little longer to enroll? What can you share right now with us?
Yeah, we're really very happy with enrollment now and feeling confident that we will meet that Q1 of next year full enrollment.
Full
... for the 360 patients. It's been really good momentum we've seen in the screening activity, and you know, we're going to be. Europe is back from their August vacation now, and this is going to be an important time for us. We'll be at ERS showing our collagen PET study data, having investigator meetings, pushing on all fronts to really have a strong participation of Europe as we get into the fall. Yeah, I think that you know, the challenge is competition, of course. The BI PDE4 phase III trial is fully enrolled, so that's not a competition for us. BMS phase III is ongoing, but we are not hearing a lot about this program from our KOLs, and we would expect to hear a bit more.
True.
So we think maybe it's, you know, there seems to be that a potential issue with hypotension with the LPAR that BMS is developing, which could or could not be a concern, but this is something that maybe is something to watch out for because they went to a higher dose in phase III also, that they did in phase IIb. So our safety profile really came across very clearly to all the investigators, and I think the, you know, the once-daily administration, the good safety profile, and all the translational evidence we've generated, we feel is really putting our program as really competitive out there.
Got it. And again, key question here is always going to be how well will the phase II replicate in a phase III trial, right? So I don't know, what can you say in terms of powering assumptions, kind of your degree of confidence that the 12-week data could actually replicate or get better over time as you move out to a 52-week endpoint, which is standard? How should investors think about that translatability of the data generated so far versus any protocol changes, differences in background therapy, powering assumptions, so on? So it's a big picture question, but
Yeah. Yeah, no, that's fine. So what we looked at from an effect size perspective is trying to replicate what we saw at 24 weeks for the 320 milligram dose, the difference between active and placebo, and accounting for higher standard deviations, potentially. And so we've been really conservative in our assessment, because what we're trying to replicate is what we saw at 24 weeks, at 52 weeks in BEACON.
Yeah.
Right? So that's. We're not extrapolating or-
Well,
Exactly. So we're thinking we're in a really good position there. We have a lot of quality checks in terms of our trial, where we're monitoring also FVC standard deviations throughout the study. So if there's any sites that have higher deviations than you would expect, we can retrain them. So we really want to put an emphasis on quality. And, you know, we think that there's a really high-- we feel confident about the phase IIb, the way we designed it. And then also for phase III, we have an opportunity to change the sample size based on the phase IIb effect, right? That's why we haven't disclosed the final number of phase III, because it will be informed-
Got it
... by the phase II results. And if we have even a stronger effect than we expected, then we're in a great position. And if we're a little bit not as, you know, maybe the effect size is a bit less, we can still adjust for that in phase III. So it feels like we've de-risked the program as much as we can.
And in terms of mono versus background, so again, you had 80% integrated, a smaller study. I'm assuming here you're enrolling more naive patients. So what, what's the split and how that changes some of the-
The minimum?
... assumption?
Yeah, so that's a great question.
Yeah.
Sorry, I didn't answer that.
No, no
... first time around. But, yeah, the minimum we're targeting is at least 30% of patients on, not on background therapies.... They can have been pretreated before and discontinued, or they can be truly treatment naive. But we want to start generating evidence in the monotherapy setting and comparison to true placebo as well, because we think given the efficacy and safety profile we're seeing from this drug, there's a great position for it potentially in first line as well. So, and 30% will be our minimum target, and we'll see if we can do better than that. But, really, the hope is to really start, you know, having strong data on that, on the drug by its own, right? Not just combined with standard of care.
Yeah. No, that. I think that's fair. And again, we've been talking just about FVC, 'cause that's kind of the registrational endpoint, but you also have the cough data, the imaging data. Like, how do you contextualize that versus standard of care and kind of the overall product profile? Because, again, there's always a concern about patients feeling better, how does that translate to quality of life, so on and so forth. So how should we think about some of those secondaries?
Yeah, so I mean, one of the secondaries we'll be looking at is the time to disease progression, so that's the standard-
Yeah
... composite endpoint of looking at, 10% or greater decline in FVC percent predicted, respiratory-related hospitalization, and all-cause mortality. So we'll be looking at that. We'll also be looking at the subgroups of patients on and off background therapy, to see where, you know, is there an opportunity for us in phase II, like in phase III, to get power in the subgroups? So we could potentially, if the drug gets approved, see that in the label, so we, we can promote to it. So that's, that's something we'll be looking at very closely. And then we're also including QLF, in, in the BEACON-IPF study. So we want to also continue to showcase the antifibrotic activities and also biomarkers.
And so the last point you mentioned, PROs are being included, so Living with Pulmonary Fibrosis is one, and then K-BILD are two, PROs that not only look at cough, but also other domains like, you know, that affect the activities of daily living.
Got it. No, I think that's fair. And inevitably, let's talk about what's success, right? And I think in this particular case, that's related to different patient populations, so on and so forth. So again, based on the data generated so far, is there a clear signal of a difference in incremental efficacy on top of standard of care versus treatment-naive patients? I'm curious how to think about the bar for success across those two patient populations, 'cause... So let's start there. Just from an efficacy perspective, would you expect to see a substantially different benefit for naive versus patients on background therapy?
What one would naturally expect is that if you're compared to true placebo, your effect size should be greater, right, than if you're-
Sure.
... dosing in combination. So that's why we're excited about having a greater proportion of patients not on background therapy, 'cause it could be an opportunity-
Got it
... to really show, you know, the treatment effect in a patient population that's just receiving that drug. So I mean, for me, success is really meeting the primary endpoint overall-
Mm-hmm
... so that's going to be really important. But if, you know, we continue to see the favorable safety and tolerability profile we've seen, that would be a big win because there's a lot of limitations for the approved drugs today. A lot of patients can't tolerate them. 30%-50% of patients who start therapy discontinue within one year, or they go through dose reduction, which means they're not being treated with the approved dose, or they quit. So, I mean, that's so it's not. And there's a substantial proportion of patients who just don't want to initiate treatment even, right? So there's an opportunity there for a drug that's really well-tolerated.
And then, if we're able to show effect on cough again, and also the antifibrotic activity through QLF and biomarkers, I think we have a really strong program and a strong product that can be really competitive out there.
Got it. And again, kind of difficult to talk that specifically about your competitors' data, but so far, if you look at phase II or phase III data sets that are out there, how do you think Bexotograst stacks up? And I'll unfold that into two different questions. So there's an implied assumption that eventually IPF will move towards polypharmacy, right? And how much of that may impact the commercial opportunity for your asset, and how much that will impact your positioning versus competitors? But also mechanistically, what do you think you do that is different than some of the other later-stage assets, and how that may play out in the future if you do indeed get into a polypharmacy backbone?
Yeah. Well, I think we have to assume that the generics will be prescribed, right? They're... I mean, Ofev is going to be there, Esbriet will be there. So we've designed our program to be as broad as possible. So we want to see what our effect is on top of those for patients who are tolerating those medications. And we want to be able to capture patients who are either new to treatment or who don't tolerate the approved agents. So there are other competitors out there, as you know. BI is there with a PDE4 inhibitor in phase 3. BMS is there with their LPAR that Eric mentioned. There's a couple of others as well. We are, as far as we can tell, the only pure antifibrotic.
You know, LPAR is sort of in that same vein, but the TGF-beta pathway is upstream of that. We think, based on the copious amount of translational work we've done, we've shown, you know, that all of the sort of biomarkers, all of the imaging data, all of the approvable endpoint measurements that we've looked at sort of point us down the same path, so we think from an efficacy perspective, we're in a very competitive position, having shown an increase in FVC across a number of cohorts, but from a tolerability case, or I think, you know, that differentiates the scene even more. Ofev, you've got a significant diarrhea signal, similar with Esbriet, similar with the PDE4 from BI.
These are older, more frail patients, and that diarrhea can actually be a significant life-altering AE for them to have to deal with. BMS drug is a little bit cleaner. They did, they'd have an hypertension signal. Now they're testing a dose twice the size they tested in phase two B, so we'll see how that goes for them. Their effect was somewhat modest in their IPF phase two B trial. So from a tolerability perspective, I think we've shown a very competitive profile, having, you know, no dose relationship, no drug-related SAEs. From an efficacy perspective, you know, we want to, we want to. So far, looks really good, but that's why Eric wants to, you know, make sure that we see monotherapy, combination therapy, have the broadest label we possibly can.
Got it. And perhaps just a final one on the commercial opportunity here. So again, it's a relatively well-established market, $4-$5 billion already, where there's a ton of data to suggest that patients are treated suboptimally or that not enough patients get their full prescribed medication, so on and so forth. So what are some of the key levers here for you to actually gain share in that market over time? Assuming there is, like, a treatment-naive opportunity, like you mentioned, there might be a switch or a combo opportunity. Are you taking share or being added to, or are you growing the market? Because, again, I think the numbers can get big quickly, depending on some of your assumptions. But what is your base case right now in terms of how that can play out for Bexotograst?
Yeah. Well, I think we can do a couple of things. I think we can capture patients earlier whose physicians are not putting them on treatment right away due to the fear of tolerability issues. I think we can actually treat patients for longer. So Eric mentioned, patients don't stay on the drug for that long. And what we've heard from investigators is that patients don't mind being on our drug because they don't feel any different. In fact, some of them have reduced cough, and so they in some ways, you could say they feel better. So we think we can have patients on drug for a longer period of time. And for the patients who don't tolerate one of the two approved therapies, we think those patients have a viable alternative.
You know, the market's at $4 billion today, and we think it can grow over the next 10 years to $9 billion or $10 billion.
I think one maybe thing to mention is PPF, for example, is an interesting way to grow your market, right?
Sure.
That's kind of the really the playbook right now that the other sponsors are using. But I would say that having a really well-informed phase four lifecycle management plan-
Yeah
- is probably where you can really be very competitive, right?
Try to form it out.
Especially if you have a drug that's well-tolerated, that's very effective. You can see all kinds of clinical scenarios where that could be applied. So we're already starting to think about that.
Yeah, and the slide deck, you guys added a couple of things around there. So, like, where do you think there would be the strongest scientific rationale in terms of the ILD, other types of ILDs? So, like, what could be the next step here? And again, capital time constraint, all the const... But longer term, where could this make a lot of sense mechanistically?
I mean, it's what we haven't, you know, fully fleshed out, and we're also looking to build our medical affairs group. So that's something that's forthcoming, and we'll have a lot more interactions and thinking about the lifecycle management, what needs to get done. But some interesting tidbits about some of the advisory board we ran over the past few years. Clinicians that are treating these patients are starting to say: Wow, if this drug is really as well-tolerated in late-stage studies, I can see a time where I'm going to switch my patients off quicker from what they're having, or I'm going to switch them to a different, or to your drug if they can't tolerate. So you're starting to hear these just switch for tolerability, switch for failure discussions.
We haven't really dove into that, but we're seeing. I mean, there's a new wave right now. The first wave, it's been a decade now since the approved agents. So I think there's a lot of creativity that we can bring to the table when we think about, you know, the second wave of IPF drugs and how we do it. But I do think there's a great opportunity there. Because if you think ultimately in the treatment guidelines, that all the four major pulmonary associations, right, including ATS and ERS, Ofev and Esbriet have a conditional recommendation still, right? So there's a lot more headroom to position your compound or your drug really in a higher ranking or higher recommendation. I think that's what I would be looking for as well.
Gotcha. And again, just for completeness, PSC, I don't think there's a lot of investor expectation around that program anymore. It sounds like there could be a path forward from a regulatory perspective, but where do you stand on that right now? Is that something that is worth pursuing at this moment, or it's something that, again, you're focused a little bit more on IPF? How should we think about optionality right now in PSC?
Maybe I'll handle just to take the clinical part, but-
Yeah.
So for us, you know, it's fair to say that from INTEGRIS-PSC, we saw antifibrotic properties and also benefits across all the different assessments that really highlighted the effects of Bexotograst, and it supports also Bexotograst and IPF in a way, because we really see the good tolerability, but also the antifibrotic activities. But we need to do further dose ranging to select the phase 3 dose. So the FDA was supportive of us doing it, like a two-dose phase 2b, with a 52-week duration and selecting the dose based on non-invasive tests. So that's great. But they were not in a position to comment on a phase 3 endpoint. So that, for us, is a, you know, we went in with wanting to get clarity on the path to registration. We didn't get. We got clarity-
Got a half answer.
But we got a half answer. So for us, it really becomes a little bit challenging to know, if you would get into phase IIb, what are you gonna be measuring in phase III?
III.
It might. If it's different, is it really helping you?
Yeah. So like, as Eric said, we think the drug will work in PSC, and we'd love to move it forward, and we're gonna continue to look for a way to do that, but from a company perspective, with our current capital, we see value in IPF, and as Eric mentioned, broadening into PPF in the pulmonary, on the pulmonary side, so we're gonna look for ways to accelerate an expansion into PPF, if we can. And we think we see the greatest value creation there, so I think, unfortunately for PSC, we're... Given what we know today and given the capital that we have available today, we won't immediately be launching a phase IIb there.
Got it. I think that's fair. Yeah, I think that's fairly consistent with investor expectations, but I appreciate the additional background. We are running out of time, so I just wanna give you some room to talk about some of the earlier stage programs. So again, oncology, I don't think I ever got a single question about that. Like, I don't think there's a lot of focus there, but again, TGF-beta historically has been implicated in studying that. So can you just talk about that program, the next steps, next milestones, and we can probably leave it at that if we have enough time? So, yeah.
Yeah. So we're in the third cohort of five possible cohorts in our dose-ascending phase I. It's an all-comer study. You know, this program was spawned from interest from pharma.
Yeah.
So the mechanism's well known. It's understood. We wanna get that data. We'll have safety data with, you know, in mono and in combination with, with pembrolizumab. We'll have PK data, and we'll have some PD markers that we'll be looking at for, for tumor activity or activity in tumor microenvironment. With those pieces of data, we think we can have a package, that will be attractive to, to a partner. So we don't, we don't have an oncology franchise. We're not looking at, you know, changing direction of the company, so we'd like to put that program in the partner's hands, who can really drive it forward.
Got it. And then just the muscular dystrophy part of the story, what's the status there? And again, doesn't feel like it's a big part of the story-
Yeah
... right now, but just how to check that box as well? So.
Sure. Yeah, it's an interesting mechanism. We think it actually could have applicability outside of DMD and muscle in general, so we're currently running some experiments to see where else we might be able to to have an effect and what other indications we could potentially affect. So we haven't started the phase I yet. We have cleared a CTA to go directly into healthy volunteers, but we're waiting until we know a bit more about the potential of the mechanism before, so we know exactly how to design our phase I and measure the right biomarkers there. So more to come there. We'll talk more about sort of additional indications as we learn more, but we think it could be a pretty exciting program.
Got it. Perfect. I think with that, we can probably wrap it up. So again, appreciate you guys making the trip.
Thank you for having us.
Thanks.