BridgeBio Pharma, Inc. (BBIO) Earnings Call Transcript & Summary

Okay. We will continue with the next session, which is BridgeBio Pharma. Good morning, everyone. I'm Paul Choi, the SMid cap biotechnology analyst here at Goldman Sachs. And it's my great pleasure to introduce the founder and CEO of BridgeBio, Neil Kumar, who will walk us through some opening comments on the BridgeBio story. After that, we'll go into Q&A. And as in previous sessions, if investors or clients have comments or questions for the management, in this case Neil, please feel free to submit them through the Goldman Sachs research portal. And time permitting at the end, we'll try and squeeze in a question or 2. Alternatively, you can submit questions to me directly, and I'll read them at the end, as I mentioned. And with that, I'll turn it over to Neil for some opening comments and then we'll go into Q&A.

Great. Thanks, Paul. Really appreciate the opportunity to present and field questions today, and thank you to you and your entire team at Goldman. I'll make my opening comments brief because I welcome the opportunity to get into questions. BridgeBio, for those of you that don't know, is a company that focuses on genetic diseases, both inherited diseases as well as somatic cancers, with good genetic drivers. We have over 20 programs, 8 in the clinic. And they really focus on a wide variety of therapeutic areas as well as using small molecules, gene therapies, protein replacement therapies. But what holds all of those or unites all of those programs is the theory that we're targeting well-described diseases at their source, be it TTR amyloidosis, achondroplasia, MoCD Type A, small diseases, larger diseases. What we're doing is taking diseases where one can marry the genotype very specifically with symptomatology and targeting the causal driver. And so we'll get into a variety of those programs, I think, through the Q&A with Paul, but I think it's important to remember that, that's what unites all of those programs. 2021, looking forward to next year, is going to be a big year for the company. We have a Phase III readout in TTR amyloid and Phase II proof-of-concept readouts in achondroplasia, CAH and ADH1. All of those are 500-plus million dollar markets, where we're at the best in class -- or first in class. We're filing our first 2 NDAs this year, and we have 6 programs moving into the clinic this year as well. And so it's a busy time right now. Hopefully, in the next 18 months, a good proof of principle that we have a very productive product engine. So maybe I'll stop there, and Paul can get into the Q&A, if that makes sense.

Okay. It sounds good. Thanks for that, Neil. Since you mentioned ATTR, maybe we can start there. You recently presented some updated data or some additional data and analysis from your earlier stage program here. And as you mentioned, you have an ongoing trial for it here. And so can you maybe -- for investors who may have overlooked it in the slew of news flow that's been happening recently, what you presented in terms of updated data? And how that potentially looks different versus the competition here?

Sure. Are you talking about TTR or achondroplasia?

ATTR.

Yes, okay. Well, so in the context of TTR, we've been focused on, obviously, the ongoing Phase III clinical trial for cardiomyopathy. The data that was recently presented was now some time ago at AHA, where we showed in our OLE trial a significant decrease in mortality as compared to placebo and rehospitalizations. And so that trial, as we've talked about in some detail, was slowed by COVID-19, just given the fact that the median age on the trial is 72 years old. These people are at high risk. But what we've seen, I think, more recently, is that actually probably surprisingly, quite a bit of activity in that clinical trial as people and sites started to come back online. It's a devastating disease. Now 42% mortality over the course of 30 months. And so people have, I think, appropriately started to judge equipoise and said that they would come back into the hospital to begin the trial. Though the good news is we have a small molecule, so we can directly ship that product to patients' homes. So no one we know in the clinical trial has missed a dose yet. So that is really the upcoming data there, will be our Phase III readout. We expect that it'll be fully enrolled first half of next year. And 12 months later, we'll have our own data.

Great. With regard to some of the clinical profile of AG10 here, can you maybe comment on what you like so much about it versus the competition? You said enrollment, obviously, will be completed in the not-too-distant future, and you'll have your data 12 months after that. What gives you the sort of the confidence here as -- given that it is already -- there is as an asset commercialized on the market that you potentially have the winner for best-in-breed sort of drug for this category?

Yes. It's an important question. I mean there's a multiple different ways to answer it. Going back to the genotype, phenotype in the disease, every time you do a little worse in terms of destabilizing the tetramer, you do a little worse for patients. And every time we've done a little bit better in terms of limiting the amount of monomer, that is a product of the destabilized tetramer, we've done better for patients across both polyneuropathy and now cardiomyopathy. And I think the last piece of evidence that we were waiting for was to understand whether or not the 80 mg tafamidis dose outperformed the 20 mg tafamidis dose. And recall that when that data came out and there wasn't a dose separation, I think DyDo's stock fell by 50% and people felt like, well, maybe there's a threshold effect in cardiomyopathy that's absent in polyneuropathy. We never thought that, primarily because that trial wasn't designed to discriminate between 2 doses, fourfold increase in dose for tafamidis only, at least with a 2.5 fold increase in exposure and about 13 percentage points increase in stabilization. But nevertheless, data was presented last week by Pfizer that did show a separation between 80 and 20 mg doses. Appropriately, they showed that the 80 mg dose patient population was a little sicker as they went into the trial. So that's why there wasn't a separation as they reported it out at 30 months. But suffice it to say that the stabilization hypothesis, I think, is the mass-action characteristic of this disease, which is the more bad monomer, the worst for these patients has been well established, biochemically, biophysically and now in the clinic. And we have a twice-as-good stabilizer. It's twice as good in terms of stabilization, it's 50% better in terms of CM TTR levels, it's better than either the silencers or tafamidis in terms of stabilizing that TTR, keeping it around and making sure that it doesn't fall apart. So in all of those respects, we feel like we're going to have the best-in-class compound and hopefully, that will play out in the context of the thing that people care most about, which is mortality. So now the proof will be in the pudding. Yes.

Yes, with the data, of course. Yes. Just in terms of what's happening in the market, maybe to run down our discussion here on ATTR before moving on? Can you maybe comment on what you're hearing from clinicians in terms of sort of the real-world market? What's happening there? And does this -- what's been happening sort of shape your view of the market opportunity for AG10 care in this indication?

Yes. I mean, tafamidis was a little bit slowed by COVID, but not much. It's a large product, $1 billion product-plus, it looks like, on a run rate going forward. And what we've been heartened by is the ever-increasing number of physicians that are prescribing for the first time and finding their first TTR patient. So not only do you see exponential growth, as we've discussed before, of these patients in academic medical centers, and I think UCL had a good paper on that, but you're also seeing quite a bit of novel prescription happening in the community setting or cardiac experts that sit outside those AMCs. So that's good. And Pfizer has done a great job of getting the awareness to increase and technician scanning to increase so that people who have HFpEF and other types of conditions that might -- or echoes that might suggest that they should be looking, they're starting to look now because there's something to do, there's a drug.

Okay. Great. Maybe shifting gears to one of your other advanced businesses, QED, and talking about achondroplasia. Can you maybe refresh us on the recent preclinical data you presented on that asset, infigratinib? And what you saw there in terms of the various measures on growth and velocity and so forth? And how you think that compares to some of the other competing assets in the category here in achon?

Yes. So I mean here, again, it's like with TTR, the primary cause of that disease is the destabilization of the tetramer. We know that if you stabilize it more, you'll do better. And we have a highly potent stabilizer. In the context of achondroplasia, we know what drives the disease as well, which is a DNA function mutation in FGFR3. And we know precisely what that does, which is it affects 2 signaling pathways, one is the MAPK, the other is the JAK/STAT pathway. And what we're trying to do is to target the disease at its source and tamp down both of those effective pathways. Our competitors, both Ascendis and BioMarin, are focused on 1 of those 2 pathways. And at least in the context of BioMarin, they tamped down that signaling to a very light degree. So the preclinical data that we published, as you just suggested, ENDO, show that we were a much more potent inhibitor of that MAPK signaling pathway that we were able to knock down both of those effective pathways, both the JAK/STAT and the MAPK pathway by targeting the FGFR activated receptor at a source. And fundamentally that we're the only compound, at least in the mouse model that's been faithful to clinical data thus far, human clinical data thus far, we're the only agent that's been able to show a profound effect not only on bone growth, but L4-L6, foramen magnum, all of the things that actually patients care a great deal about outside of AGV. AGV is, obviously, the endpoint that you'll trial on, but spinal stenosis and proportionality and those sorts of things are as big issues for these kids. And so our hope is that this drug administrated at about 1/100 of the adult oncology dose will be able to have a profound effect on these children.

Great. Maybe following up on that, Neil, in terms of the potential for accelerating the development process here in the achon indication. As you talk about advancing this asset, are there any steps or anything supporting, in your view, of potentially shorter developmental time line here, given that you've published preclinical model, but other -- your competitors are clearly in the clinic here with some clinical data out there already?

Yes. So we're in the midst of the PROPEL trial, where we have a 6-month run-in and then -- kind of dosing children, and then there'll be a 6-month follow-up on AGV. It's an interesting question. I mean, obviously, in the second or third cohort, we would expect to start to see effect. And whether or not could roll this trial into some sort of a registrational trial and expand around the dose, obviously, that's -- if we're seeing great effect, that's something that we could do or could think about doing. It's not something that -- our base case plan is that this is our Phase II, and then we'll run a Phase III, just very similar to BioMarin after this, once we really understand the effect of the drug and what the right dose is. So here, I mean, I think the big question remaining is, what's the right dose in terms of how hard are we going to need to go? I doubt we're going to need to go very high based on the potency of the drug. But recall, this is a FGFR inhibitor that's never been trialed in the juvenile setting, so we need to understand where the toxicity lies, if any, and go well below that. This is not an indication where one wants to be up in the hyper-fast range, which is about 40-fold higher than our highest contemplated dose. But still, we've never looked at this in juvenile. So we'll see. Yes, I mean -- seems you have some question.

Yes. Great. Yes. So as you pointed out, you're obviously looking at it at a much lower dose in this population versus the oncology indication, where you're looking for multiple indications there. So then maybe just a follow-up on that. We've seen some clinical competitive data on the slide here. What do you think as view as -- based on your discussion with KOLs and as you think about trial design, what do you want to look for here in terms of AGV? What, in your view, is considered good? And what would be you consider sort of a home run based on the early data that you might provide in the future?

Yes. Well, BioMarin has set the bar, I think, with 1.6 centimeters per year. We need to do better than that. There's no question. And how much better? If you double that, for instance, you take children all the way back to normal height. And so that's possible, I think, with a drug like this. I think we also want to be looking very carefully at differential in things like collagen 10, which is a good biomarker for bone growth, obviously. And to see whether or not we have effect on things like proportionality and others of the symptoms that I've talked out. Spinal stenosis would be hard to pick up in a trial this short. But that's the bar for me in terms of AGV is we have to mightily beat the 1.6, which -- the theory indicates that we should be able to do that. The other thing to remember in this case is -- that's a daily injection that physicians are dealing with right now. Someone said on the call the other day, they were holding their child down and injecting them every day is not fun for those of you that are parents out there as I am. And this is an oral medicine. So we hope, first and foremost, in any Mendelian orphan disease, efficacy should play out, and it's the best indicator for who's going to win. But I think besides that, the route of administration here is much more convenient for a child than daily injection or even weekly injections.

Great. That certainly makes sense, Neil, totally agree. Maybe just looking at the other side of QED here since you brought it up, on the oncology side. Can you remind us what is the enrollment status of your programs here? Maybe on the bladder side, there has been an asset they're commercializing with -- in terms of FGFR. It hasn't made a big splash in terms of the market. And then also on the CCA side, what the enrollment and update there are for that program.

Yes. So I'll start with the adjuvant side because I think there's been recent data, obviously, downstream of the adjuvant market. I mean this is a big market, 67,000 FGFR3 mutant positive patients there, and we're the first gamer sort of right now and the only trial that has been run there. We had, as we've discussed, some really interesting data in upper tract urothelial carcinoma patients in some of our Phase IIs that suggest that they should work in the context of FGFR3 mutant patients. And we expect the duration could be quite good in this setting as well. The standard of care is not chemo. So this should be a very interesting trial, where we're just up against placebo. And so yes, that's started. We've dosed the first few patients. And I think we announced that a couple of months ago. And so that enrollment is -- there's no competition there. So that enrollment is coming along nicely. And actually it wasn't that affected by COVID. On cholangiocarcinoma, we're still guiding to filing our NDA this year. So that -- so second line cholangiocarcinoma trial is fully enrolled and finished. And in first line, that continues to enroll. So it's not a huge patient population, it's 2,000 to 3,000 FGFR2 fusion patients in that context, and we're up against Insight and Taiho. So enrollment, I wouldn't say, is blazingly fast there, but it's coming along.

Okay. Great. Thanks for that, Neil. Maybe shifting gears to another asset, but staying within the realm of oncology. Your KRAS program is something you guys haven't talked about much publicly, but it's certainly in a hot area of interest in terms of investor focus, given the various approaches to the G12C side. So I think one of the next steps in that particular market is focusing on SHP2 assets there. And can you maybe talk a little bit about where you are with your preclinical program in terms of KRAS SHP2 inhibitors? And what are you seeing in these early studies that will inform sort of your next steps here?

Yes. Good question. So SHP2 is obviously -- I'll start with SHP2 because that pertains to G12C, and then I'll differentiate our program as compared to that. So G12C, which all of those drugs right now, as far as we know, are buying at the GDP bound state of G12C. It seems to be that you need to shut down upstream signaling alongside of G12C inhibition. Although the theory of the case might be, if you had a super highly potent drug, you wouldn't need that. But in any event, it does seem like you do need a combination there. SHP2 is a very interesting combination. We have data. Rev Med has data that shows that SHP2, in combination with the existing G12C inhibitors, is synergistic in a variety of different settings. Same thing with CDK406, same thing with MEK inhibitors, same thing with osimertinib and eGFR inhibitors. And interestingly, eGFR inhibitors might also, in concert with G12C inhibitors, be of interest. And I think Lilly is playing out that clinical experiment. So regardless, I think SHP2 is going to be an interesting combination agent. G12C is an obvious partner. And those experiments are ongoing. Our SHP2 is going to be in the clinic in the next 1.5 months here. So a variety of different clinical experiments will be played out. Our KRAS program is actually different than the G12C approach, although it sort of -- it stems everything -- in the field really stem from billions of Kevan's work, showing that one could think about covalent inhibitors of KRAS. We're going after a site that's actually conserved across all of the mutants H95. And so we haven't published any of the crystal structures or any of the chemistry because, why do that? It's a highly competitive space. But in this case, we're buying the GDP-bound state of KRAS, which is important, especially super important outside of G12C, and it's an approach that should work across D&V and some of the other more common mutants. So that's one approach. And then the other approach we've taken is try to disrupt the interaction between RAS and PI3K, which Julian Downward has shown, is one of the key effector signaling moiety in that pathway. So that's the approach there. We're in lead optimization. And I don't think there's much more to say about it. We have crystal structures. We have a nanomolar potency. We don't have a development candidate yet for our RAS program. And I don't imagine our particular RAS program would necessarily -- although it's too early to tell, would need to be played out in combination because RAS is a key driver. If we're potent and we have a good Ki over [ KNF ], we should be able to go as a monotherapy there, so -- but again, it's too early to tell.

Yes. That's a really interesting comment about how to view it as a monotherapy here, given that it seems like a lot of the response rates that we're seeing evolving in the market are driving the other -- companies that sort of focused on G12C towards combination regimens. So I guess...

Right. And that could be the case that you just get a little bit of -- if you just have a little bit of upstream signaling, maybe it overcomes the drug. I mean, who knows? I mean it's actually the case for any drug, our drug as well. I just don't know to what extent we'll be able to get up to that -- to the appropriate level of inhibition. And if not, then you do have agents like SHP2. And I think SHP2 is a very interesting combination agent.

Great. Obviously, as you've been talking about and as I've mentioned, the focus has been on G12C. Could you maybe elaborate on how you see the potential application of your program? And I know you're still working on candidates here to other variants or sub-variants. And how you think about the platform potentially generating additional opportunity sets here in KRAS?

Yes. So it is wholly focused on this pan-mutant approach, so it should work for the other key -- both the D&V mutations. And the signaling pocket or the binding pocket for the drug is unchanged. And the crystal structures we have are in the context of D&V. So I think, in that respect, there is nothing to say, but we're targeting one mutation and then going after the next mutation, going after the next mutation. We've gone after a conserved binding pocket across all of those mutations.

Yes. That...

Of course, there's a third approach that we've spoken about, which is going after the covalent side associated with KRAS processing, the C185 processing moiety. And that approach hasn't -- it's about the same place that it was about 8 months ago. So as we think about that one versus H95, which is progressing quite rapidly, I don't know which one is going to win. But that one is also, obviously, pan-mutant in as much as processing is required for all of these mutant KRAS moieties. So yes, that's the 3 different approaches. I would say that the momentum is behind H95 and the PI3K approach right now, but we'll have to see. They're all in lead opt.

Okay. So I think a lot of investors think of KRAS as a high-risk, high-reward opportunity. But it's, obviously, a very potentially large addressable TAM for -- given how many -- given that 1/3 of all cancers that are involved here. So in your mind, Neil, what is sort of the hurdle rate in your model? And maybe you can explain to investors how you think about allocating and funding additional R&D here, especially for a large opportunity like KRAS? And so can you maybe elaborate how you think about the internal hurdle, right, in terms of funding and advancing your efforts here in KRAS or more generally across the BridgeBio portfolio?

It's good question. Yes. So I mean, we actually think a lot about that. What's the NPV? What's ROI? What's the hurdle rate? Obviously, our cost of equity, we think is quite high. If you do a discounted cash flow against our entire portfolio, I think it's -- we're off about 50%. So that means that our cost of equity, at least, is close to 20%, and we use that as a hurdle rate when we think about modeling out each one of our assets. So in that respect, when we look at KRAS, we just use historical POTS from [ pay it all, ] and we use those numbers associated with cancer versus the ones that we use for a lot of our other programs, which are dosed for mendelian disease or orphan disease, which are quite a bit higher. So chance of preclinical to even get to an IND, the probability of technical success is something like 45%, 46%. And all the way through, the probability of technical success is something like 7%, if you have a genetically validated target. So that is literally the POTS we use in the model. Now as you say, you're talking about 1/3 of all cancers, so it's always going to be NPV positive. It's like something small multiplied by something large. But one thing we keep an eye on, I think, which is much more interesting for programs like this are a key series of go, no-gos. I mean, this is a capital-intensive program. We have 40 scientists working on KRAS. That's very unusual for BridgeBio. We usually have 5 working on a given program when we get to IND and $10 million or less. So we've had to establish some very clear go, no-gos. And if we're not able to progress certain chemistry or get, in the first case, crystal structures or actually tune up the actual binding potency beyond 100 nanomolar, et cetera, et cetera, if we can't meet those go, no-gos, then we shut the program down. And so that's what we're really focused on, on KRAS because I don't really think the numbers will ever suggest that we shut it down. It's just too high, to your point, TAM, so -- multiplied by something small. It's always going to look reasonable.

Okay. That makes sense. The math can potentially be very interesting there, to your point.

Well, it's totally unlike some of our clinical programs in smaller diseases, where, let's say, we've got regulatory feedback that we needed to run 2 trials, not 1, or something like that, then all of a sudden, that takes it from NPV positive to negative. And we would partner it or close it down at that time. And we have closed down 6 programs, including 1 clinical program just because that can happen, and we tried to set ROI bars or internal hurdle rates that are reasonable so that we're not going after super small diseases with a lot of money, which is not a sustainable business.

Great. Maybe at the other end of the spectrum versus some of your early-stage work here in KRAS. On the other side of the spectrum, you are in Phase III together with -- and you're in partnership here with LEO Pharma. And so can you maybe remind us, first, on the timing of the readout for that Phase III next year, and specifically, any more specificity when that might happen? And how do you think about that relationship evolving? Do you -- do they think that a great relationship would evolve just based on one of the indications reading out, Gorlin or the other or both are reported out? And how do you think about that? And then I have a follow-up question on that as well.

Yes. It's a good question. So we're still guiding to top line Phase III data first half of next year, I think, even despite COVID, is on trial. And LEO has an option to acquire the program based on that readout. And that would mean that they would be effectively the owner of both the Gorlin and the high frequency, where we take off that trial indications. And so we would just be kind of the counterparty receiving royalties, milestones and the upfront. So yes, we did that partnership back in the day when we didn't have a lot of access to capital, and LEO has been a great partner. So I hope the drug reads positively. But we're not, unfortunately, going to be able to be the ones who commercialize it or will own the high-frequency indication either.

Great. And then can you maybe just remind us what the economics might look like here if they elect to opt-in here on this? And how do you think about potentially utilizing those assets or that funding, given that you won't have to spend the time or effort to advance it through the regulatory stage or commercialization?

Yes. I don't think we disclosed the milestones, but it's not -- it's a few hundred million dollars that we would get from the upfront and the milestones. So that's real money for us. We have -- we're well funded into mid-2022, but we're burning about $75 million a quarter. So that's a -- that would be significantly another year of burn for us if things came through on that drug. And we would use it to fund the ongoing pipeline, just the same as we would if we were to do a capital raise. I don't think there's anything novel or sitting outside of the pipeline right now that we would focus on.

Okay. On the flip side of that, Neil, if you did have to pursue development of it yourself, how do you think about executing on that? So is that something that would be a heavy area of investment for you if you decided to take it to market ultimately yourself?

Yes. Well, the biggest expense for that program, I think, as we've discussed before, is the CMC. I mean you have to -- it's a teratogenic semisynthetic natural product, the 70-step synthesis. So that's over half the cost of Phase III that's already been spent. So actually running -- taking over the trial and taking it forward wouldn't be that expensive, but that's not happened at this point. The trials are -- well, the Gorlin trial is fully enrolled and ready to read. And I think the high-frequency trial is ongoing, and that materials has already been made. So I don't think we'll have that opportunity.

Okay. That makes sense. In terms of some of the other earlier-stage programs and other -- I'm sorry, excuse me, other later-stage programs you are -- have an interesting first potential commercial product here at MCA. And can you maybe update us on what's happening with that package and filing? And how you think about -- it's a rare and small population, a handful of patients typically in the NICU. And what's happening there?

Yes. So that's an ongoing rolling NDA submission. We've submitted a majority of the modules. Now that's a drug, as you mentioned, that is for mSv type A, and it's really a profound drug for a small number of patients. I would say, unlike cancer, in the orphan space, you can run these franchises of $100 million or $200 million drugs in a profitable manner. You're talking about just a couple MSLs, talking about a lot of physician education, to your point, in the NICU. And the key here really is that if a child is born indiscriminately seizing, how do we get people to think about this disease? How do we get people to think about sell-side buildup to do either a tandem mass spec experiment or another type of easy diagnostic experiment before the genotypic experiment so that we can get people on the drug? And we have the saying in that team is time is brain. The earlier you get these children on drug, the much more profound the effect of the medicine. So what we want to do is actually make sure that -- it's a extraordinarily safe drug. It's a monophosphate, and there's no MTD at all. And so if you suspect that you might have this disease and you test positive on a biochemical assay, we would want people to go on drug. And then if they have -- there's 2 mutations that might occur if you were to have that type of buildup. It could be MOCS1, loss of function, or MOCS2. And if it's 2, then you've come off the drug. If it's 1, then you could stay on the drug. So we would want to get as many people on the drug as possible, and then take them off if they don't actually have the genotypic confirmation. But yes, that's kind of the approach.

Okay. Great. [indiscernible] Maybe one more pipeline question in our remaining couple of minutes here, which is on BBP-589 in RDEB. You have Phase I/II data coming out here. Can you remind us what we should look for? How this trial is framed and set up? Is it -- should we primarily look for safety? Or on the efficacy side, how do you think about presenting data there? And then I have a follow-up to that, Neil.

Yes. Well, safety is a big deal, obviously, because this is an IV-administered, pretty massive protein. And so far, it has been very safe. So that was a big issue going into the trial, I think the issue that we explored very carefully in nonhuman primates as well in our preclinical work. Efficacy is also important. Obviously, this is the only game in town in terms of dystrophic epidermolysis bullosa that's a systemic product. So it's not topically looking at a recurring wound. It's actually, hopefully, if it works treating the diaspora both in symptomatology on the skin, which are chronic and recurring wounds as well as mucosal membrane damage and internal GI and other types of distress that these patients unfortunately have to bear. So we would be looking for dose-dependent increases in collagen VII. We'd be looking for function through NC2 staining. We'd be looking to wound healing, obviously, to see whether or not the drug is actually affecting wounds, both chronic and recurring wounds. And then we'll actually be using a variety of different exploratory endpoints to see if we can pick up impact on things like GI distress on some of the biomarkers that one sees that are systemic associated with anemia and other things that these children suffer with. Things like diet and appetite, I think, will also be an interesting thing to look at. So we've got a number of exploratory endpoints that we'll also be looking at that could be potentially part of the registration trial if the drug works.

Great. To your point, you're obviously focused on collagen here. But in terms of some of the other sequela that you mentioned, do you think that's something you'd pursue in terms of the label? Admittedly, perhaps that's a bit of an early question to ask as we think about this opportunity. But there are other things sequela. Are you talking about GI and so forth? Anemia?

Yes.

I think is it something that makes sense in terms of potential claims and specific to the indication?

Yes. I think that's a combination of what we see in the trial, obviously, specifically in the extension part of the trial. So we're in Cohort 4 right now, and then those patients will extend out for some period of time. I don't think within a short period of time that the trial is ongoing we're going to see the totality of the systemic effects that one might see through the OLE. But at the end of the OLE, we'll have a conversation with clinicians, with -- actually patient and parent advocates, and obviously, with our data in hand to understand what that registration trial looks like and what those endpoints will be. But my hope is, yes, it's not just about wound closure, it's going to be about something even beyond that because this drug should affect those things in a positive way.

Great. Maybe in our last minute or 2 here, Neil, there's a lot going on at Bridge. It's a lot for investors to get their arms around often. But if you have to maybe talk about 1 or 2 preclinical programs that you have here -- maybe are still early, I'm kind of under investors' radar, if you have to call 1 or 2 out here, which of them -- which of these 1 or 2 are you most excited about sort of debuting or bringing more into the spotlight in the next year or so that you think could drive the Bridge story here?

Yes. Which of my children do I like most? I think the -- I mean we've been very excited about our CAH program, 21-hydroxylase deficiency. People know the indication, I think, from the work that Neurocrine has done. And this is really -- I think it's the second-largest gene therapy market out there, and we're the only people playing in it. We're using [ precedented backbone ] and AAV5. The preclinical data is really compelling. You need very low BGC numbers to phenotypically reverse the disease, and we've been able to really efficiently and durably transduce the adrenal gland, the adrenal cortex. So that's a super exciting program, and it's headed into the clinic next year. It's preclinical now, but it's headed into the clinic late this year. And we'll get proof-of-concept next year very quickly. Because I think the other neat thing about the program is you're going to actually start to see, if the thing is working, endogenous cortisol production in these children for the first time. And so what excites me about it is you don't need that much of the enzyme to actually be present in adrenal gland to do something pretty special. It's a siP enzyme. And so 10% of wild type is all you would need to actually get to a pretty profound effect. So that one is super exciting, I would say, of all the stuff we're working on. And maybe LGMD2I as well, which I don't think a lot of people have focused on. But that one is headed into the clinic. And actually, we just announced this morning, first patient in the trial. So it's -- and that one is substrate replacement. It's a big market. We're the only players there. We can measure glycosylation through a pretty simple but elegant biomarker assay. So we should find out pretty quickly how this is working, and it's a profound unmet need with lots of patients. And as far as I can tell, we're the only players there as well. So yes, those are 2 interesting programs.

Great. Thanks for that, Neil. Yes. So limb girdle is definitely a very interesting space and opportunity for you as well, in addition to CAH. So unfortunately, we've run out of time here, Neil. We'll have to end it on that note. My thanks to Neil and BridgeBio for participating here in the Goldman Sachs conference. Thanks, Neil.

Thanks, Paul. See you.

Take care. Bye.