Are we live? We're good? All right. Excuse me. Good afternoon, everyone. My name is Corey Kazimov. I'm one of the senior biotech analysts here at Evercore. And it's my pleasure to host our next discussion with BridgeBio. Thrilled to have you guys here. It's been our top pick for 2025. So thanks for coming through for us. Most of you probably know Chinmay, but we're also very, who's SVP of strategic finance and IR. We're also very excited to have Justin Toews, the CEO of QED Therapeutics, which is Bridge Bioskeletal Tysplasia subsidiary. So great timing, giving the pending phase three readout of Infragratinib in the first quarter of 26. So thank you guys both very much for being here today. You know, to kick things off, and I'll say we have an extended conversation with you, so that's good too. To start things off, it's a little bit of a loaded question with some very obvious answers. We're asking this of everybody as 2025 comes to an end and you look back on the year. What would you say were the company's main accomplishments? I guess this is a good opportunity for you to briefly recap what has been a very eventful and transformative year.
Yeah, happy to talk about that. Maybe I want to first start by saying thank you, Corey, to you, as well as the entire Evercore team, Brad, Hank, and everyone else. We really appreciate you inviting us and hosting us. And lastly, and obviously, a huge thanks to the investment community for supporting us throughout the year and joining us on our journey to help patients with rare diseases. So 2025 has been a transformational year for Bridge Bio. I would probably start by saying that the most important accomplishment this year has been a phenomenal launch of a Truby. We were very confident that we would be able to launch it to be very successfully, get it to a lot of ATTRCM patients. We knew that it was a large market. We knew that we have a differentiated label. We know that we consider it to be the best product for treatment-naive patients in ATTRCM. Having said that, the execution by our commercial team has been phenomenal this year, And I think that we ended last quarter at a run rate of about $440 million in revenue. Beyond that, we've also read out two positive phase three data sets. And I just wanted to take a moment to talk about these data sets because it is rare in our industry to find data sets which are curative. So most of the times, as all of you know, when we are looking to make a drug, we are just trying to slow the progression of the disease. Once in a while, you get an amazing drug like a Truby, which fully stabilizes the disease. However, with both N-calorate as well as BBP418, what we've been able to show is that not only did we stabilize the disease, we actually have started to cure the disease. In N-calorate, we cured it in about three-fourths of the population. And then with BBP418, that's the first molecule which is shown in muscular dystrophies, an improvement in function compared to a placebo, which was declining. So it's been a very eventful year. We're very excited about all the progress. And so that's where we are. That sets us up very nicely for 26 also. And maybe what I'll say is I think about the company in terms of just two numbers. We're going to make it simple for folks. I know there are lots of conferences going on. So the two numbers that I want you guys to remember are one is $6 billion and the second is $10 billion. So what are these two numbers? So $6 billion is what we consider as their fully de-risked peak year sales potential in our pipeline today. So that's $4 billion for a Truby and a billion each for both in Callerit and BVP418. That gets you to $6 billion. The second is the $10 billion number, which is the peak year sales potential of this pipeline. And in the remaining $4 billion, I account for Infragratinib, which we are going to turn over next year in Achondroplasia. That's a couple billion dollar opportunity at least. And beyond that, we're going to start a phase three trial in chronic HP, which is another huge opportunity. We're going to use NCALEREC to go from the genetic form of hyperparathyroidism, ADH1, to the broader population. And then we obviously also have programs in hypochondroplasia, which are going to treat out its phase two data set probably by the end of the year, as well as working on Fukuyama disease and LGMD2M and 2U. So it's a very exciting time for the company. We have de-risked $6 billion of PKR sales, and I think that next year we're going to make good progress in terms of further de-risking towards that $10 billion number. And, of course, that's the opportunity if you look at our market cap today for investors.
Six and 10, I like that. So just to level set where we'll go here, we'll start with the Truby, and we'll quickly touch on your recent phase three wins. And then, Justin, be patient. We'll get to plenty of questions to go on Infragratinib. So, you know, starting with the Truby, you know, focus more on the big picture, long-term potential of the product. And you kind of just touched on this. When you think about the ultimate sales potential here, you know, in the context of the view that the ATTR-CM market could be at least $15 to $20 billion overall, are you surprised that consensus peak sales expectations are still, like, below $3 billion?
Yeah, I think that we have said publicly that we believe that a Truby is going to be at least a $4 billion product. So, you know, there's no doubt that this is a $15 to $20 billion market. The market continues to grow, and I'm happy to spend more time talking about it. Beyond that, I think it's very clear we today have north of 20% share in the treatment-naive setting, which is the most important setting. We also get a lot of switch patients, which is great. So if you just look at what we have today and you look at the size of the market, which I don't think is disputed by many on Wall Street. If anything, people think it could be higher. You do the simple math and you get to the four billion plus numbers. So I think that that is an area of opportunity for investors as we continue to execute on a Truby and we go from 108 million in quarterly revenue to a higher number. I think that people get more cognizant of the opportunity and hopefully that's going to reflect in the stock price. I don't know if I have any views on consensus, but I'd like to reflect it in the stock press.
And now there are obviously a fair number of investors out there that worry about the future entrance of Tafaminis generics. To that end, you're generating a pretty broad set of data to position Atruvi as the stabilizer of choice. Can you kind of walk through the key data sets that support that view at this point?
Yeah, that's a great question, Corey. And I think that I want to first start by looking at our label. So that's data which is on our label today, and you guys can go read it up, it's on the FDA website. So we are, number one, the only near-complete stabilizer. This is extremely important. You don't see the near-complete verbiage on any of our competitors, whether it's silencers or stabilizers. So that's the first thing, because this is a disease of toxic monomers, so near-complete stabilizing the toxic monomer means a near-complete stabilization of the disease, which is obviously what we are looking for. The second thing which I'll talk about is the time to separation in terms of hard outcomes or the time to onset of effect. So we have shown on our label that our outcomes separate as early as three months, and we've done further work, and we presented this at HFSA to show that actually they separate as early as one month. So that, again, is a very important data point because these are older patients, they're very sick, and they want to feel better quickly. And everyone wants to, you know, That helps with the long-term stability on the therapy too because if you're feeling better, you're more likely to stay on the therapy than if it takes months for you to see an effect and feel better. The third thing is obviously hospitalization and mortality where we have the best point estimates at 30 months. So at 30 months, and I think it's important to look at the right time point, at 30 months we have a 50% reduction in cardiovascular hospitalization which is extremely important for payers and a 42% reduction in mortality and hospitalization. Now beyond that, we've continued to generate a lot of clinical evidence. So this year, for example, we have shown that if you add a TRUBI on top of tefamidus, you get a sharp increase in the serum TTR levels. Meanwhile, if you add tefamidus on top of a TRUBI, you don't see that effect. And I'm sure some of you are wondering, why is he talking about serum TTR levels? We've also shown this year in the manuscript that increases in serum TTR levels are predicted are shown to actually be related to decreases in all-cause mortality. And in fact, the increase that we saw on a Truby is predicted to have about a 15% reduction in all-cause mortality versus tefamatis. So this is the kind of data that physicians are looking for. They're looking to see what happens if they had a patient and they switched them on to a Truby, what kind of benefits you should expect. And the ultimate benefit is reduction in mortality because that's the most important thing in many ways. So that's one dataset which we've already published. Now beyond that, we have shown in various subpopulations such as the variant subpopulation where we have the best point estimate that those are the sickest patients. And that's also patient population just severely underdiagnosed today, so I think that there's gonna be a lot of growth there. The second important subpopulation where we have shown an effect, a strong effect, a very strong effect is the AFib population. So recall about half of these patients, half of the ADTRCM patients have some component of AFib. And we have shown the best point estimates in terms of reduction in AFib-related events compared to all other therapies. And it's important to note that some of the knockdowns actually go in the reverse direction in terms of AFib. We don't know why that happens, but that is what's been shown in the data sets. So I think that we have continued to generate evidence. We are a science-first company. It's one of our core values. And I think you can expect us to continue to do that more in the next year. So we're very excited about switching studies and looking at biomarkers like NT-ProBNP. We're very excited about imaging studies. We are huge fans of real-world evidence, and so we are very excited to have a TRUBI-B out there in the real world and for physicians to now ultimately compare what happened to their TRUBI patients versus their defamitous patients. And I think that as the cacophony of data continues, I think that we are going to be able to convince more and more physicians that a TRUBI is a differentiated product. It's not just another stabilizer. It's a unique product. It offers unique potential. And as you have seen in every other commercial class, even if a first to market less potent molecule goes genetic, the second to market more potent molecule continues to grow, nothing happens to its sales, because ultimately this is a deadly devastating disease and physicians want their patients to be on the most potent molecule. So that's kind of how we're thinking about it.
Okay. What's the current desire to run a head-to-head study against tefaminis that's focused on some sort of biomarker, NT, ProBNP, or something like that?
Yeah, I think we're considering it, but I think at the same time, we want to generate evidence which is going to result in increases in share. So we are obviously scientifically very curious about all kinds of things, but I think scientifically, we are very convinced, just given the work we have seen in the serum TTR and the connection between serum TTR and mortality and hospitalization, that it's a superior product. So for us, it's focused on what do we think physicians are looking for, and I think so far what we've seen is they're more excited about real-world evidence and some of these switching studies and imaging studies that we're doing as opposed to a true head-to-head study.
Okay, all right, so let's, in the interest of time, let's move on to Incaloret for ADH1, and you've talked about this being a billion-dollar-plus market opportunity. What are some of the key assumptions that go into that when you think about the size of this market?
Yeah, so a few assumptions go into that, right? So obviously, simplest level, you have the number of patients who are treated, and then you have the price. In terms of the number of patients who you could treat, recall that there are about 12,000 patients who are carriers in the US and about 25,000 in the US and Europe put together. So that's the size of the opportunity. Now, if you look at the serviceable opportunity today, you don't think about any increases in diagnosis, which has happened with every single genetic disease out there. But let's say you feel like this is unique in some way. We have identified about 3,500 patients in the U.S. today, and we have about another 1,500 that we suspect have ADH1 just based on their EMR data. So that is the 3,000 to 5,000 opportunity today in the patient population just in the U.S., right? You have a similar sort of phenomenon happening in Europe also because our trials are all global. If you think about that and you think about any kind of rare disease pricing, right, I think that on the low end what we tell people is you can look at things like Chris Vita, which is about 400K or so, Voxo, which is a similar price, and you can look at some of the more rare genetic diseases like the exon-skipping drugs as well as Prader-Villai and things like that, and those drugs can be north of 750K. Even if you take the conservative end of that price point, you can easily get to a billion dollar opportunity just in the US, and then you have Europe on top of that. Now, what's very important about this is that And Calrate works in all ADH1 patients. And this is another amazing thing, and you can probably hear the excitement in my voice, and some of you know me well, and I usually don't get excited about data like this, but it's remarkable that we went from a phase two study where we had a 70% point estimate in terms of resolution of the disease. We're talking about full resolution of the disease with normalization of blood and urine calcium. And in our phase three, we went out, we had significantly more clinical trial sites, significantly more variants of the calcium sensing receptor, and we were able to improve our point estimate. To me, that's extremely rare, and you don't normally see point estimates improving in the phase three compared to the phase two. So I think that this drug is very important and it works on all these ADH1 patients. So I think that that is how we think about the opportunity.
Okay, great. So when you take this the next step when you think about post-surgical hypoparathyroidism, how do you respond to investors who argue that calcium sensing receptor antagonism in Caloret wouldn't work in PSH? Like what preclinical or clinical data support your view that it can in fact work in that setting?
Yeah, that's a great question and I'm glad you're focusing on the broader chronic HP opportunity because it's a huge market and we're very excited about it. We're gonna kick off a phase three trial next year. So what I would tell those investors is very simple. you should go look up our phase two data set, which we published in September. We took patients who were the sickest of the chronic HP population. They had no PTH gland, right? So we're talking about folks who could not produce PTH. We gave them incalorate, and incalorate only works on the kidney, as I was describing earlier, and we were able to show that 80% of the patients had normalization of both blood and urine calcium. And when we have done our market research and why we were so excited to take this in our phase three trial was we saw three axes of differentiation for this molecule. One was normalization of urine calcium, which is a huge unmet need in the HP community. We were able to do that at an 80% rate, same as the blood calcium normalization. The second is an oral option. And I think people underestimate commercially how important it is to just have the convenience of an oral option as opposed to an injection every day where you're going to have injection site reactions and all kinds of things. So that was very exciting to us. And the third thing is just the safety, right? And so there is a theoretical bone resorption risk with chronic PTH therapies. We act completely orthogonally, so we don't have that kind of risk. And now we've even shown in the incalorate phase three that the molecule was remarkably safe and well-tolerated. So I put all the clinical data together on the safety and the efficacy side, including the fact that we have shown efficacy in patients who have no PTH whatsoever. That gets me very excited about the phase three for chronic HP.
Great, great. Okay, so next up is BBP418 for limb girdle. And I guess, you know, why do you view, like the data that you had, why do you view this as an unprecedented outcome in muscular dystrophies?
Yeah, that's a great question. And again, it gives me an opportunity to talk about the wonderful data that the team has generated. We're incredibly proud of it. So let me just put the data in context for folks who don't fully know what we showed. So limb girdle muscular dystrophy is like all other muscular dystrophies, a disease where patients slowly lose function over time, right? So they are slowly not able to walk properly. Their lungs don't work as well. And that's a slow deterioration, which eventually obviously leads to mortality. And we have a small molecule which works on alpha-dystroglycan, And we were able to show that by supplying a lot of the substrate in that pathway and increasing the flux through that pathway, we were able to actually start to show improvements. So for example, you know, not only did we show a statistic effect on the biomarker alpha-DG, both at three months and then that increased at 12 months. You also want to see things like that. So very excited about the biomarker data. That corresponded to a statistic drop in CK. Again, extremely excited about that. But what's been really phenomenal is just at 12 months, this is the first muscular dystopia that I'm aware of where we saw a statistically significant effect on clinical endpoints, you know, functional endpoints. So for example, 100-meter time test, right? So we saw that patients on the placebo arm were declining in function, and patients on the drug arm were actually improving in function. So this gets to my point earlier that the disease was not stabilized. You actually saw an improvement in the patients. We saw the same thing in FVC, and I think that we've not seen effects like this. So that's gotten us very excited about this data.
Okay, so then how do you think about both the initial market opportunity for this program, and then what's the plan to tackle other subsets of the kind of the broader limb girdle indication?
So the opportunity here, Corey, is about 7,000 patients in U.S. and Europe. And again, if you look at the same kind of genetic disease price analogs that I was mentioning earlier, you can easily get to a billion dollar plus opportunity just with limb girdle muscular dystrophy type 2i. Again, you know, similar to ADH1, we have a huge apparatus identifying these patients and we have a lot of patients already identified, thousands we know already of. Beyond that, there's an opportunity to expand this population by about 50% just through, you know, expanding into LGMD2M, LGMD2U, Fukuyama disease. And so we're doing a lot of work on that front. And I actually think it's also interesting to just note this tidbit that if you look at the pace of enrollment of the LGMD2I trial, that suggests actually a prevalence much higher than 7,000 globally. So we'll see. Once we're out there on the market, we don't want to be ahead of ourselves. But, you know, maybe there's an opportunity to just increase the LGMD2I awareness and patient population. And beyond that, there's probably a 50% increase by these expansion indications.
Okay, great. All right. So, Justin, finally, thank you for patiently waiting. Finally, time to dig in on infagratinib and the opportunities in skeletal dysplasia. So I guess maybe let's just start with the basics. And if you can just briefly walk through infagratinib's mechanism and how it differs from the current standard of care, maybe the key pros and cons versus the other approaches.
Yeah, happy to. And, again, thanks for having us here. So infagratinib is the first oral therapeutic option for the treatment of achondroplasia. And more importantly, it's the first targeted treatment for achondroplasia. So for those who are less aware of achondroplasia, it's a disease caused by gain-of-function mutations in FGFR3. And so Infragram is an FGFR3 inhibitor. Other drugs like the CMPs from Biomir or Sendus only target the MAPK portion that's downstream of FGFR3. But in achondroplasia, not only is there over-activation of the MAPK pathway, but there's also over-activation of the STAT1 pathway as well. And so, you know, because of that, InfraGroundup is the only therapeutic option that can target both pathways, which we will think it's pretty essential to really have impact on achonplasia itself. And so in our Phase 2 data, we saw best-in-class improvements in change from baseline age fee, you know, change of plus 2.51 at month 12 and plus 2.5 at month 18. Not only that, but we were really the first trial to show any type of statistically significant improvement in proportionality, something that the patients and caregivers really care a lot about. Proportionality basically is kind of how high your torso is compared to your lower limbs. And kids with achondroplasia have significant disproportionality as well. So we think that between kind of the mechanism, the preclinical data where we showed significantly more bone growth and our phase two data set, that this could be, you know, just from the efficacy perspective, a very compelling treatment for families. But more importantly, I think, or just as importantly, I think the fact that this is the first oral treatment is something that should not be overseen because it's something that comes up time and time again when talking to caregivers and families.
Right. Okay. All right. So as we dive in a little bit here, I want to start on the safety front because I think it's where we get most of the questions going into the phase three readout that's anticipated in the first quarter. and there's some concern out there on the risk of hyperphosphatemia. Can you frame the safety profile in the context of what's been seen to date?
Yeah, let me kind of frame it again. Let me just talk about what's been seen in the phase two, but then also then take a step back and talk about why we're not really concerned about hyperphosphatemia. So in our phase two trial of about 72 kids, there was only one case of mild transient hyperphosphatemia, notably not even at the clinical dose we decided to go forward with for phase three. You know, so our cohort 5, which was the main data set that showed the results I talked about earlier, had no cases of hyperphosphatemia. There was one transient case just barely above upper limit normal in a lower dose cohort. Now, taking a step back, though, when we talk to clinicians and talk to KOLs, they're really not worried about hyperphosphatemia because what is hyperphosphatemia? It's transient increases in phosphate levels. And we know that other growth-promoting agents, such as growth hormone, whether it be daily or weekly, in their labels, they have rates north of 20, sometimes 30%, 40% of hyperphosphatemia, and they don't require any type of monitoring requirements. So pediatric endocrinologists are really familiar and comfortable with transient elevations and phosphate. And so for us, we think that for our phase three, honestly, anywhere south of 20% would be quite manageable and fairly looked at from clinicians.
Okay, so you anticipated my next question, which is like two-part in how confident you are that you won't see a high rate and you sound very confident, and then kind of what incidents would you consider acceptable? So it's somewhere below 20%.
20% of low-grade hyperphosphatemia.
Okay, and I mean, even 20%, though, would you expect to see a number like that when we didn't see any?
Yeah, again, until we run the phase, so we don't know, but we always want to think about, again, from the clinician's perspective, what matters for them and what can drive usage, and that's kind of a number that we've heard of, like hey if it's out of that we're not too worried about that especially since we know that the daily and weekly growth hormones have rates north of that yeah okay all right and then you've already
touched on this but if you can go in a little bit more into it and the kind of characterization of infagratinib's efficacy to date in terms of the annualized growth velocity proportionality and
other metrics that you'd be following yeah so uh the questions were about you know the primary endpoints and the secondaries that we were measuring or kind of the data that we saw in
The kind of how the phase two, you would think, translates into phase three is really one to go with it.
So, again, the primary endpoint or phase three, it's going to be a 52-week trial, about 110 participants, two-to-one randomization between treatment and placebo. The primary endpoint for this is the same in our phase two, which is the change from baseline and annualized height velocity. You know, the secondary endpoints, there are two key ones that we're following closely. One is improvements in height Z-score, which I'll get back to that shortly. That's a very important one. And the second is improvement in proportionality. The main difference between our Phase 2 and our Phase 3 is that in our Phase 2 trial, it's studied kids between the ages of 5 to 11. In our Phase 3, we're actually going after a broader population, looking at kids 3 to 18. This is slightly different from what Biomarin did and slightly different from what Ascendus did, which I know gives investors headaches because we can't do a proper cross-trial comparison. So Biomarin did 5 to 18 for their initial trial, and Ascendus did 2 to 11. So we're actually kind of, this phase 3 will be the broadest population that has been studied in achondroplasia. And the reason for that is because we want the broadest possible label, especially given the strength of the data that we saw in our phase 2. The trade-off, though, is we know that kids who are younger, so like the ages 3 to 5, and kids who are older, so 11 to 18, we know from the other trials that there tends to be less of a treatment effect because those kids just don't grow as much. So we do expect a bit of a diminution of the treatment effect from the phase 2 to the phase 3 because of that. And so I think for us, anywhere north of like 1.5 centimeters per year will be great to see in our phase 3. But more importantly, or just as importantly, this is why I mentioned that one of our key secondaries is change in height Z score. So this change in height Z score will probably be a great friend to investors because it's actually a really helpful way to compare across trials. What height Z-score is, is effectively it normalizes the change in height based on a participant's age and gender. So it basically just looks at the population mean and kind of plots it compared to that. So Byron and Ascendis both saw an improvement in height Z-score on average of plus 0.3 from the A-contemplation population mean. So I think as long as we can see that, I think that can kind of show you some comparability between the trials.
So I guess, can you follow up on the anticipated, like what you think would be a positive efficacy outcome? You said anything above 1.5?
Yeah, and the reason why, you know, we didn't pick that number out of the ads, which I would love to say about it. You know, we did a lot of market research, talked to clinicians, and did a number of surveys and panels. And the number one thing that comes across from these discussions is The number one biggest driver of potential adoption for a new therapeutic is the ease of convenience, the ease or convenience for families of around administration. That was the number one thing. They're like, if all else is equal, if efficacy is the same, in a three-way marketplace between Vimerin, you know, Ascendis, and Infragrana, over 50, sometimes 60 percent of clinicians would rather just pick the oral. And we think that number is even higher for families and caregivers, right, just because, you know, who wants to be injecting their kid, you know, every day? And so that's why we think 1.5 is the bogey for what's going to be a commercially successful launch.
Would you plan when you either top line this or when you provide more detailed data, a future medical meeting, would you provide data kind of stratified by age groups that would enable people to sort of compare your phase three data more apples to apples with your own phase two data?
So, you know, at our top line, I think it remains the same because, again, we're going to have to release data pretty shortly after having it. So we're going to be prioritizing the top line, which is the population mean, and the key secondaries for a top line. Probably for major medical conferences, we'll look more into kind of producing some of the subgroup analyses. Although, again, the caution here is even though it's 110 participant trial, the subgroups are all probably going to be quite small to compare between the trials. This kind of goes back to an earlier point, though, that one of the best ways to compare across trials will be looking at a high Z score just because that kind of normalizes across three trials based on the different population, like ages and genders as well.
And when you go back to the phase two, I wanted to ask about kind of the trajectory of growth that you saw because you had cuts at month six, month 12, month 18, and you saw obviously the big jump, and then that attenuated a little bit and then was stable out to month 18. How would you explain that trajectory that you saw?
Yeah, so this kind of phenomenon of kind of like a spike in month six and a steady state from month 12 to 18 is not specific to infra-granum. It's something you kind of see across all achondroplasia trials. And it's almost like a statistical kind of noise based on the way the endpoint is measured. So the endpoint is annualized height velocity. So you basically measure how much it grows, and then you try to smooth it out across a year. So when you look at it, when you do it across six months and you annualize it, basically any noise that's captured in the first six months gets amplified by two. And so typically, you do want to look at month 12, month 18, to have a smoother age fee and so we're confident it's not some sort of like weird one-time signal one-time noise or loss of effect because what you see from month 12 to month 18 importantly is that the treatment effect effectively stays flat you know it was at plus 2.5 point in month 12 plus 2.5 the month 18 okay
and then with competitor trials and ascend us specifically with our long acting CMP I mean they showed stronger outcomes in phase three than they did in phase two do you any takeaways from that experience I mean you've you've broadened your age range for phase three so it's you want wouldn't see that dynamic at play but anything from that that kind of informs how you think about
infragratinum no I think again it's hard to kind of comment on the specifics of their trial and I will say across all the different phase threes in this space whether it be barman system and ours site selection is similar right we all kind of use the same centers of excellence all use the same ways of measuring endpoints so it's kind of hard to kind of talk about what happened in their trial and going from phase two to phase three but I don't kind of anticipate kind of one-off trends happening in one trial that aren't seen in other trials just because we're all using the same sites and centers of
excellence okay and then I mean I guess to put it bluntly like what do you see as the main risks going into phase three I mean you sound very confident talking about it but what are the what are the risks there what what worries you yeah
I mean, I think for us, you know, we talked about the efficacy signal, right, again, and I think based on what we saw in the phase two, we felt pretty good of being able to hit the bar of 1.5 centimeters per year for age fee. I think the biggest risk, and I don't really kind of see this as a risk, but there might be a misconception that just because we hit proportionality in our phase two at month 18, that we're going to for sure do it again in our phase three at month 12. And to be honest, it's going to be a little bit of a coin flip. You know, we don't necessarily we know whether we're going to hit it or not just because no trial has ever seen an effect at month 18, let alone at month 12. So, you know, I think if we're measuring this endpoint later on at month 18, month 24, I think there'd be a greater chance. But at month 12, I think it's going to be a little bit of a coin flip. And if we were able to really hit at month 12, I think that would be a home run
for us. Maybe I'll also just add, it's similar risk as all our other trials, right? If you think about it, we went from cohort five, which was tens of children to now phase three, which is more than a hundred children. And so you have more sites, just more heterogeneity. And as Justin mentioned, one of our learnings has been you want the broadest possible label at launch. So we also broaden the age group. So there are multiple things here which should attenuate the signal. And so it remains to be seen if we can replicate strong data and get above 1.5 centimeter per year. But I think that until we do the experiment, we won't know. We feel good about doing the experiment, but we cannot predict the outcome of it.
Okay, I guess, well, there's a few questions, so a few directions I want to take this. So it sounds like you would expect, if this trial goes as planned, that your initial label would include ages three and up. Is that right? How difficult is it to dose a three-year-old with an oral formulation?
Yeah, I think it's a great question. So I think there's this misconception that infrarotib are like horse pills, and you take several of these horse pills a day. So it's a once-daily capsule, and the capsule itself is quite small. This capsule inside has small mini-tablets, anywhere from three to five or seven or so. And these mini-tablets are each the size of, sorry, one-third the size of a grain of rice. So very easy to take. These mini-tablets can be sprinkled on food, sprinkled directly in a child's mouth, or the whole capsule can be taken intact as well. And from our discussions with sites, it has never been an issue to administer, even to the youngest kids.
So three-year-olds don't have trouble getting – I mean, I have two kids. I've seen – when they were three years old, food ends up everywhere. So if you try to put it in food, like to be sure that you're getting the proper dose taken by the kids.
Yeah, no, it's definitely been a really good experience with the sites and the caregivers where, again, And I think the families are very thoughtful about how to administer to the kids. Every family situation is different, but we haven't really ever heard of issues of administering to young kids.
Actually, Corey, I'll just add, we've invested a lot in this formulation. So this mini tablet concept that Justin's talking about, there's profound innovation there just in terms of making sure that, you know, a small child can also easily take the drug. So I think we don't talk about it a lot because it's not sort of, you know, PhD science. but it's actually quite innovative as to what the team has done here.
And then BioMarin's Voxogo is approved from the time of birth onward, and they talk about most of their use now is in those infant patients. Can infagratinib, can the formulation ever be updated or even needs to be updated to get down to newborns?
Yeah, so two things there. One is we will be eventually starting our trial in the youngest kids looking at kind of infrared and kids from birth two or three so that we can ultimately update our label to include from birth just like with Vox Ogo as well. So that is going to be a key priority for us. To your point around the formulation, so the youngest kids, kids from birth to six months, probably will need some different type of formulation, which is something we're actively looking at. But kids from six months and up would be able to take the current formulation.
And does your market research suggest if a child is on Vox Ogo or eventually on Ascendis' Transcom product, once they've been on it and they're doing well on it, that they would still switch over to Infragratinib because it's a oral pill?
Yeah, so we've done research in both the Truman Naive, which I want to come back to in a little bit, and the families who are currently on treatment today and trying to understand switch dynamics and adoption dynamics. And we've heard resounding interests, even from families who have been on Vox Ogo since the day it was launched, to switch to an oral formulation. So I think there's really no degree of necessary stickiness just because if you've been injecting your kid every day for a few years now, you don't necessarily get used to it per se. I think you still want to look for a better treatment option, especially as they kind of get older and you have to adopt with your daily routines as they grow up as well.
I guess just to be clear, is your view on Infragratinib's kind of value proposal, Is it changing at all to be more in line, efficacy-wise, but with the convenience factor of being oral? Or do you still anticipate that it's going to be the most efficacious of these products as well?
Yeah, I mean, ultimately, I think it will have to depend on what the phase three will show, right? Because I think in my hard hearts, and from talking to clinicians, they understand the scientific appeal of having something that is truly targeted, not only hitting the MAP-K pathway, but the STAT-1 pathway as well. And whether or not that gets borne out in a 12-month trial versus longer-term data Other important endpoints remains to be seen until we kind of see the phase three data But I think at the end of the day We will kind of be able to find some see some data that shows that having a targeted therapy will have treatment effects Over the long run that are better than that of the CMPs That being said though, right? So even if we don't kind of see that in a 12-month trial I think the value proposition of having the daily oral is going to be a very key driver of adoption. And there's two reasons for that. One, again, going back to what we hear from caregivers, the route of administration is the number one kind of importance factor for families looking to switch today who are currently on therapy. And second, I know a lot of noise has been made recently about Voxoca's recent performance in the U.S. there's a sizable proportion of patient and patients and families in the United States I would say close to 60 70 percent of the US market there are not on treatment today and that's not because they don't want to be in treatment in fact most of these families are interested in treatment they're just kind of on the fence right now because a conglomerate is not lethal condition and how do you win over a family that's on the fence about treatment not with a daily injectable right and so these families many of them are actively interested in treatment but they want to be better than the daily or weekly
injectable and that's where we come in. Okay something else we hear in our in our KOL conversations and we see advocacy groups talk about this as well is kind of this almost frustration with this overly lines on growth velocity for these kids. You know you speak to proportionality and things like that that you'll get in your in your data set you know these benefits beyond just height I do you expect this to be reflected in your label and how important is it that that is there the end of the day yeah I think there's a
few things about that one is that we will be continuing to study and for granted beyond just the phase three fifty two-week trial right looking at other endpoints over time that we can hopefully see important improvements on whether it be skeletal health like Boeing spinal health quality of life and I think that is gonna be really important for families that who care about outcomes beyond height you know whether or not you know that ends up on a label I think that will kind of depend on discussions with agency and what's within scope and out of scope. But I think we're going to be really thoughtful and aggressive about publishing to make sure all the available science and data is out there to support why we think Infragratinib is the best agent out there.
And then assuming the phase three trial goes as you hope and this is on the market, how do you see Infragratinib kind of performing and competing as what would likely be the third entrant? Where do you expect the initial share to come from and how rapidly do you see that market evolving?
Yeah, I think the market will evolve quite rapidly. From the families who are already on therapy today, we know just from our experience with clinical trial sites that there's a lot of pent-up interest from families who are on Voxoil today to switch to daily oral once it's approved. It might not happen overnight. Obviously, no launch has a rapid switch overnight, but we know the interest is there from our discussions. And I think just as importantly, I think InfraGrant will be the first program that could unlock that Truman IAE population today, which is a huge number of families in the United States.
Right, okay. You know, Biomarin has talked about the fact that 75%, 80% of global Voxelga sales are outside of the U.S. How quickly can a company like Bridge ramp up the kind of the OUS capabilities?
Yeah, let me talk about that in two ways, and I feel free to jump in later as well. I think Biomarin really focuses on the ex-U.S. side of things just because they don't really want to talk too much about how the U.S. market is underpenetrated. I think that's an area of significant growth for us when we come in, right? That population in the U.S. who are either needophobic or aren't interested in daily injectable today for other reasons. I think that's going to be a clear growth area for us that's still quite untapped. On the ex-U.S. side of things, I think we're going to be well-prepared, not just for InfraGradNet, but for other franchises as well, to launch and win a good share, throw it out and share. And the reason for that is, you know, these centers of excellence is not like a Truby where it's disparate and like 40 different sites in a given country. There's only about three or four experts in any kind of given major market country, and we already know who they are. We've worked closely with many of them. Some of them are clinical trial sites today. So I think we're going to be quite effective at being able to drive adoption in major ex-U.S. markets as well.
Maybe I'll just add that we've actually built an extremely strong XUS team. And remember that even for Acramatis, you know, if you look at all the XEU geographies, you know, whether it's Brazil, whether it's Canada, Trish Bio is the commercializing entity. So we know that even for Acramatis, we had to build a big, you know, we had to have an international presence. And then with, you know, extremely strong data sets in ADH1 and Limgirdle and obviously really excited for the Infragratinib potential opportunity here, we've gone ahead and we've hired a few extraordinary individuals. Actually, the person used to be a senior Alexion executive commercially now heads our international office. Actually, Justin's being a bit coy, he just came from our international office, so he's met all of them. And there's a lot of cross-country travel that's happening. So I think you guys know that we're not shy in terms of getting on a flight, seeing our people, and making sure things are going okay.
So I was going to ask, because we kind of round out this conversation, you're going to be filing at least two, maybe three new applications. Each of these products has global ambitions. I was going to ask how difficult you think it's going to be for a company like BridgeBio to pull this off. It sounds like you can do it, and you're already well on your way. I guess the next question that's tied to this and then the question we get frequently from investors is, do you have the balance sheet to pull this off? And what kind of levers can you pull to address the lingering investor concerns on this front?
Yeah, I'm happy to talk about that. So we have about $650 million of cash on our balance sheet today. If you look at our spend, it's been roughly flat over the last three quarters. And if you look at our revenues, they've gone up. So that makes it to be a very good financial situation where our burn keeps dropping. Our expectation at Bridge is that even with filing two and hopefully three applications both nationally and internationally and then commercializing potentially up to three products and running all the expansion indications, we don't really expect our cash burn to go up. just given the fact that Truby continues to inflect in its sales. And so, you know, you take that burn into account with the fact that we have a very strong balance sheet of $650 million of cash on hand. And if you look at our debt situation, you know, we have $1.8 billion of debt, but about $1.2 billion of that or $1.1, $1.2 billion of that is converts, which are deeply in the money. So we don't really have to worry about that in any way. I think we put all of that together and feel really, really good about where we are. and the business which we can build based on the potential of our drugs here.
Awesome. Well, we're down to 15 seconds. I think we'll end it there. It's going to be exciting to watch this all evolve. So thank you guys very much for being with us here today.
Thank you, Corey. Thank you, Adi, and thank you for recording.