We're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies. Thanks for joining me today. And it's my pleasure to have the Bridge Bio team with me. To my direct left is Tom Tremarchi, CFO. And to his left, Anant Sridhar, CEO of Endocrine Disorders. Welcome, both of you.
Thanks for having us. It's great to be back in New York, sun shining. The next one in the finals. And we're Jefferies, so what more can you ask for?
Great, great, great, great. So those in the audience less familiar with the Bridge story or revisiting it, would you mind just briefly giving us an introduction about it, where you are with all your programs? Congratulations on all the success, by the way. And then milestones over the next six to 12 months would be very helpful.
Yeah, of course. So BridgeBio Pharma is a company that's about 10 years old now, and we were really built to deliver patient impact at scale, specifically focusing on patients with genetic diseases. And in the first decade, I think we've been remarkably successful in pioneering a fairly new and innovative R&D model that's yielded the commercial and late-stage portfolio we have in front of us today, which includes a Truby, which is about a year into the launch, and it's really still ramping we're annualizing about 720 million dollars in the sales in the u.s and also have seen strong uptake xus with a partner buyer so so that's i think the the first leg of the stool or chair and right behind that we've got three products that have now that are now on the other side of uh really remarkable phase three data sets that we're focused on submitting to the fda and global regular regulatory authorities and we'll be launching starting at the end of this year. So that's one in limb girdle muscular dystrophy type 2i, BBP418. We see this as a huge unmet need. It'll be first drug to that market, clear billion-dollar TAM for us. Right behind that, we have incalorate for hypoparathyroidism, with our first indication being a genetic subtype called ADH1. And Ananth is here with me, so hopefully we can spend a good amount of time on that. And then third will be infragratinib. So that's a small molecule oral FGFR3 inhibitor for FGFR3-related skeletal dysplasias, starting with achondroplasia with an expansion into hypochondroplasia. So that's a multibillion-dollar opportunity for us, clearly. So a lot to be excited about. Yeah, I think the next 12 months are going to be, I think, focused execution, where we can keep rolling on Atruvi, keep seeing strong uptake, importantly, in the first-line treatment in a naive setting. And we'll be really putting our heads down and focusing on getting our next three drugs approved on time, hopefully with the right label so that we can go and deliver these
medicines to patients. Fantastic. So maybe starting with a Truby, it's doing very well. You're capturing, like you mentioned, a lot of first-line market share. I think it was above 25% recently. That's right. And so the question is, how are you exactly doing that? Because you aren't first to market per se, yet you're doing this. There's no head-to-head study been done against Pfizer's compounds. So what's resonating with doctors and so forth?
Yeah, so it's a great question. So I would say going back to the design of the molecule, we made the Truby specifically to be an ultra potent kind of next-gen TTR stabilizer. Remember, this is a disease where your TTR tetramer is unstable, falls apart, makes amyloid, goes to your heart, ultimately kills you, right? So we engineered this compound to be maximally potent against stabilization, right? So we're 90% plus stabilizer, near complete stabilizer per our label. And so that is the foundational scientific differentiation of this compound. And what we've seen that yield in the clinic is distinct and differentiating data on basically everything we can measure. Going to our primary analysis from our phase three study, where we saw market-leading efficacy, and our key marketing messages are 340-250. That's three months time to separation, a 42% reduction in overall survival events, and 50% reduction in hospitalization events. Really compelling data as physicians look across the space at what else is out there. And I think, importantly, the time to separation is particularly clearly distinct from the other options. We've also shown more recently, if you look at not time to first event, if you look at recurrent events, we're actually seeing a separation almost immediately at one month. So that's really meaningful to physicians. And so that's the foundation of differentiation. We get asked by investors a lot about how do you plan to differentiate? Well, if you're reaching for a Truby, you already believe it's differentiated. So 25% and growing in the first-line setting, you know, one in four patients are getting this because their physician believes it is the best drug for them and it's differentiated. So I think we have to continue driving that message home, and we do that in various ways, right? We have a constant stream of new data that surrounds this core message, 342.50, a lot of data in subpopulations that are pretty compelling, whether it's AFib or the variant patients. I think looking forward, some of the new data in the real-world evidence domain is going to be really important and impactful. That's starting to come out right now. We'll have more to publish on that front as well. So to give physicians a little bit more of like a contemporaneous apples-to-apples comparison against the famidus, which I think is going to stack up favorably as the clinical trial data have as well.
That makes a lot of sense. and so q1 uh you did about 180 million uh fifth quarter a full launch that's that's up from 145 and when i look at the trajectory it's pretty linear it's quite amazing to see it's not decelerating um first it's kind of a narrow-minded question but you know q2 how does volume look you know the weekly patient ads is it consistent and then second part of that would be um q1 there's technically seasonality and yet you were able to manage to get sales to grow linearly so it wouldn't queue to accelerate uh on you know gross net improvement for instance yeah that's a great
question so um maybe let me start on on the second part of the question and i'll weave in and you know into my answer like hitting the first part as well so the point about seasonality um in one queue i understand that basically you're saying if there's a structural headwind in the funnel in one Q, shouldn't that be a big boost as you look sequentially to second quarter? We didn't see any seasonality. So we didn't see anything in the funnel that suggested an unusually poor conversion from demand to sales. So that was pretty consistent with what we've seen in the quarters leading up to it. So I wouldn't expect that headwind to tailwind dynamic, 1Q to 2Q. What we are seeing, which we're happy to see, is a steady and consistent improvement in kind of like that average weekly new starts number. I think that's a product of two things. One, our ability to continue capturing share in the frontline setting. And two, a market that continues to expand. On the first part, we talked about the reasons why. Right. I think increasingly physicians are seeing a Truby as the right option and they're getting more and more familiar with how to use it, how to get it, all of that. And we've made it very easy to do all of that. So that's driving share. The market is continuing to expand. I mean, this time last year, I'd have told you we think there's probably two to three thousand treatment naive patients coming to the bottom of the funnel every quarter. That looks more like three to four thousand now. So and we don't see any signs of slowing on that front. So I think that's how I'd...
So momentum seems strong. You'll generate some more real-world evidence to further solidify your positioning. So I think at one point, correct me if I'm wrong, you've kind of mentioned, oh, we think... No, I could be wrong. But you mentioned maybe we get 30% peak market share. You're already at 25%, so why couldn't this be 50%? This is just a very conservative statement from you guys.
I mean, look, we're a bunch of former scientists or current scientists in this company, and so we're very data-oriented. And the 30% to 40% comes from market research we've done. So before the launch, that was coming from a survey of around 200 prescribers, and we've refreshed that along the way and continue to think 30% to 40% share of frontline at peak is the right number for now. Obviously, we hope to push that higher. but we're still in the early days of launch and I think that feels like the right range given where we are now but you know when we're when we're in that range hopefully soon above 30% maybe it's time to think okay where could this go what's what's this what's kind of like the upside here okay and then maybe
two more it's more investor related questions before we move on to the pipeline I just have to ask I just you know there's generic vendor call that could be available 2028 i think it's one filer um and then generic vinda max i think there's three that pfizer settled for 23 mid 2031 mid 2031 so uh the question is like if generics can enter why is there not a price vortex why is there no um volume change affecting a truby uh at the end
of the day yeah i think it comes back to the way this product is positioned and viewed increasingly as the best-in-class differentiated stabilizer and the right drug to start your patients on. So I think the good news is we have almost six years to continue hammering that message and growing that belief in the marketplace before there's a generic defaminus. And our hope is that when that eventually does happen in mid-2031, but really the theoretical pressure would come in 2032, too, that by then it is very clear to patients, prescribers, payers, that the best outcome is going to be had by starting a patient, hopefully early and on a Truby. And there's going to be a health economic argument there, too. So it's better for the system to put a patient on the drug that's going to stop their disease and to prevent them from going to the hospital and to make them feel better and live longer. So that's the most important thing we will do. um so no change in strategy is a result of the dynamics around you know other products in the class and i think we're we're very confident that this is possible right to continue growing our brand through emergence of a generic in class the reason for that is because if you look at analogs where something similar has happened it's almost always the case that if you have a differentiated product and you're able to communicate that to the market that you can continue accelerating growth through emergence of a generic we've seen this in spaces like the antigen receptor you know inhibitors with Xtandi and Cytiga we've seen it in pH we've seen it in you know a lot of
different categories thank you and so the other line of investor questioning I'm pretty sure you'll respond in the same way but I'm just curious ionis has their Carter transform data coming up in second half 2026 it is you know I my understanding a proportion of patients could be on combo with two families for plus ionis and so if that succeeded how should we think about that because there are no ionis plus a true be patients in that study is my understanding so it you You know, investors feel a little bit, they don't know how to think about it. So what's your kind of view about that?
Yeah, so first, I mean, this is a large, well-powered study in our minds. So we think it's going to be successful, and we think it'll probably hit in all of the important subgroups. So just in terms of, like, what we're planning for, that's clearly the scenario. What do we think would be the impact of that on the marketplace? Well, if that increases the view that combination therapy is interesting, particularly in second line where we're seeing it mainly today, although there are some prescribers that are able to start patients on a stabilizer and a knockdown today. If that becomes a more consensus view from prescribers, we'll continue to communicate to them that they should put their patient on the best stabilizer. And they already increasingly are reaching for a Truby with that in mind. And so really we're talking about instead of a Truby monotherapy and Truby Plus, a knockdown. And if the doctor thinks that's appropriate for the patient, I think that's fine with us. Interestingly, and we said this on our last earnings call, we've seen, I think, about a tripling of our share in the combination setting over the last several months to the point where in patients that are receiving combination therapy, we're nearly at parity with tefamidus as the stabilizer in that combination. So I think continuing to hammer the differentiation messages that serve us well in monotherapy frontline will also help us if the market, you know, trends towards more combination use as well.
And then just to add on that, implicit in some of Tom's comments is if that is where the field trends with the data, it's important to recall that the way the paradigm and the treatment regimen is studied in that approach is stabilizer first, then knockdown added on. And so, like Tom is suggesting, really capturing frontline share remains our priority and will continue to be that case regardless of the outcome. Exactly.
Regardless, congratulations on the strong execution. More to come. And so shifting gears enough to you then on ADH1 and Calaret, I think the NDA, remind me, was it submitted in May? Okay, so you should get some kind of acceptance July. And so, well, I guess for both of you. Anyway, do you expect an adcom for this program?
We would not, no. An adcom would be in a case where the risk-benefit profile is ambiguous. I don't think there's a debate on that in the data set we've generated.
from our phase three. And so my understanding, there are no drugs approved for this indication, ADH1. Remind us the prevalence and what percentage of those, in the U.S., what percentage of those patients are diagnosed, identified, ready to go by the time you launch? It's a great question. So if
we look at the general population genetics databases, so UK Biobank, Geisinger, TopMed, all of us, NHLBI, they all concentrate and triangulate to about a 1 in 25,000 estimate for the carrier frequency of gain-of-function calcium-sensing receptor variants, so that approximates to about 10 to 12,000 patients in the U.S. As of the latest cut of the claims data, there's about 2,000 patients that have been claimed as ADH1 patients as of the end of 25, so that would approximate about 1 in 5, 1 in 6 have been diagnosed. So there's certainly a reasonable population to launch into. Again, like you mentioned, there's no other approved agents for these patients today with a reasonable opportunity to grow that with increased disease awareness. One anecdote that we saw from the data from 25 alone in the ICD claims, it's about 70 new patients are being claimed a month on average. And it's a fairly linear trend, at least, that we saw last year. And we'll continue to monitor how that evolves this year.
and have you as at bridge um found all these patients with the icd-10 codes to be clear do you know where they are you know where they are yes when we when we have access to these
icd-10 uh data sets we are able to see institutions down to the mpi level where where patients are
being claimed and okay i would just say like the work between now and the early innings of launch is to get out there, confirm that they're ADH1, make sure they've had the right genetic confirmation so that they're actionable early on in the launch. Our team is in the field. Our medical team is in the field. Our sales leadership, including Anand, they're out in the field doing that, obviously in a compliant way today. And we'll continue doing that over the next year plus.
And for a prevalence size of this in the 12,000 or so U.S. patients, what kind of pricing power do you think you have, especially given the level of robust Phase III data that you've generated? How should we think about the bookends?
Sure, that's a great question. So in our emerging and maturing conversations with payers in the U.S., what we've heard pretty consistently is that the payers are going to evaluate this condition in terms of its prevalence, like you're suggesting. So single high-digit thousands is the price point that payers would manage the drug to label. And wherever that would index us is products like Chris Vita, Skyclaris, Tringolza. Those are products that have price points in those rare prevalent conditions that would bracket probably the pricing opportunity that we see as reasonable to payers.
I see. So even within the 2,000 diagnosed patient pool, that's a huge, that's a big number on that kind of price point. Okay. And so then should you be approved, let's call it January of 2027, how prepared, when do you exactly launch specifically? And like, why can, why wouldn't
there be a bolus? Or are you expecting a bolus? So we, we would be prepared and intend to launch soon after PDUFA date, similar to our dynamics with the Truby. We've developed the muscle power and the infrastructure and the systems to support that cadence of launch is certainly something we intend to continue. And then in terms of the rate of adoption, there's going to be identified patients that we work through the data as well as our field interactions to drive diagnoses like we've discussed. Paired with just an understanding that the visit frequency doesn't suggest that everyone shows up to their doctor's office on day one. Typically, the guidelines recommend about a Q3 assessment schedule for these patients with their specialists, but that translates more into, you know, every four or five months, every six months sometimes, depending on people's lives. And so there is going to be a natural cadence to an initial launch adoption curve that depends on visit frequency as well as specialist interactions.
Understood. And so as we think about it, the beauty here is each of your products have light cycle management opportunity. So you're starting a hypo-PTH as a phase three study in the summer? 26. And so remind us how long it took you to do the ADH1 study from start to finish, and could it be a similar time frame for hypo-PTH?
Yes. So it's a great segue. We are intending to launch our Reclaim HP phase three study of and choleret and chronic hypoparathyroidism this summer, so in the coming months. And in terms of the cadence of the study, we think we're planning for a six-month study analogous to our ADH1 program, but we think the enrollment opportunity is far more rapid. Relative to ADH1, there's precedent set here in terms of disease identification. The prevalent population is far more emergent. And so we believe that there is an opportunity to have a rapid enrollment curve with a six-month study. So lifecycle management is really exciting here because with a successful study, we could have a potential indication expansion into a broader population soon after a PDUFA date.
And at the end of the day, for HypoPTH, is it your guys is thinking that you might show superior efficacy relative to the competitor?
Yeah, one of our design tenets that we're excited about is that we want to elevate the assessment of urine calcium, 24-hour urine calcium, in the primary endpoint to assess the response rate to incalera. And why we think this is really important is it is an important surrogate for renal health, renal outcomes, that really does play a long-term effect in these patients' lives. And it's something that's currently not reflected on labels for replacement hormone. And it's something that we think can not only differentiate incalorate from an evidence perspective, but also in terms of its use in terms of driving urine calcium down. As of today, replacement hormone probably normalizes urine calcium about 60% of participants in their phase three. In our phase two Sentinel study, we saw 80% of individuals not only normalize urine calcium, but also blood calcium. So there is an opportunity to demonstrate a differentiated benefit on both metrics. And we're excited to evaluate our drug on that basis.
So I think in the post-surgical population, if we can replicate or even come close to what we've seen already in phase two, that'd be differentiating alone. Plus, it'd be an oral option in what is going to be a very large market where, you know, there's definitely a need for multiple types of products. On top of that, I think the non-surgical population is one where we could really be viewed as the best treatment option. and there's a big need there, right? Like, these are patients that I don't really know that PTH replacement makes a lot of sense, and basically untapped market opportunity for us to own. On top of, by then, ADH1, hopefully it will be, you know, in the early days, but well ramped up and, you know, in part of, key part of clinical practice.
Okay, great. And then moving on to LGMD, which actually could be approved later this year, And before I forget, all three of these programs, my understanding, you get a PRV voucher if they're approved?
We will get one for limb girdle. We don't expect to get one for incalorate, just given we have a pediatric study ongoing, but it's first approved in adults. And infagratinib, we may get one as well.
Okay, great. And so LGMD-2I, again, another strong data set. I think you've mentioned the patient prevalence is around 7,000 in the U.S. and EU. what percentage of that 7,000 is actually in the U.S. And by the time you're approving, what kind of line of sight do you have in terms of number of patients you've found?
Yeah, good question. So about 7,000 U.S. and Europe, there is a bias towards Europe due to a founder mutation in Northern Europe, but we see about 2,000 to 3,000 here in the U.S. based on genetic prevalence estimates. Most of those are going to be symptomatic and in need of therapy. It's a muscular dystrophy. It's evident that you have an issue, and actually it's a really terrible condition where, although it's not as rapid deterioration as something like DMD, it is a steady kind of torturous loss of function every day. So her huge urgency to treat here, I think, is what we'll see. um i think the the thing that we need to do um you know for the next couple years is drive genetic diagnosis to be at a more complete level right now most of these patients know they have a type of muscular dystrophy many of them know they have a limb girdle muscular dystrophy but until now there's not really been a need to genotype and determine that it's a a two eye versus any of the many other types of flim, girl, mustard dystrophy. I would say the plus here is a fairly concentrated site of care. In the U.S. at least, there's around 166 MDA centers where about half the patient receive care. And in those centers, testing is much more prevalent already. But we need to drive that to be at a more complete level. And we also need to drive testing in other sites of care.
Understood. And here, the patient prevalence seems like it's even more rare than ADH1. So going back to pricing power, I mean, is this kind of a D&D exon skipping type of pricing, which is like a million?
Yeah, I wouldn't put an exact number on it, but we see here the bookends are something like Chris Vita to the exon skippers. Certainly, that's the right range to think about. I think there's a tremendous value proposition here with this product for the system, for patients certainly, and for providers. If you think about what we've delivered here, I think this is, I think, differentiated amongst all neuromuscular data sets, honestly, where we've seen in a well-controlled study an amazing effect, consistent effect on all of the important clinical endpoints that we measured. But importantly, and I think some people miss this, for patients that randomized to 418 in our study, the mean actually increased across all these measures or improved across all these measures, meaning the patients are doing better on drug than they were doing off drug, whereas you typically think about in muscular dystrophies, how can I just stop the decline or slow the decline? We actually gave back function, both mobility-type measures, lung function, so really, really amazing outcome. And so we're hopeful that in our discussions with payers that we'll be able to price this well.
Right. And then the same compound is going after 2U, 2M, Fukuyama, I think. Are those next trials going to be phase threes, straight to phase threes?
Yeah, so 2U, 2M, as well as expansion into a broader pediatric population will happen starting now. So basically those will be label-enabling studies. Fukuyama, really interesting Japan-centric opportunities, about 2,000 patients in Japan. That will need probably a little bit more work with the regulators to determine the exact registration path. But we're working on that right now as well.
Okay, great. And then in the last couple minutes, achondroplasia, I think, is the NDA filing in Q3 of this year? Second half, yeah. Second half. And so I guess you're unique here relative to the competitors, not only being an oral, but with great data, but I think you're the only one to break through designations. So are you expecting a priority review, and is there going to be an adcom?
I would not expect an adcom, although we'll know more once we've submitted our NDA and heard from FDA at day 60. We may be eligible for a priority review voucher, so that's interesting as well in terms of liquidity. And I think you're right. I mean, this molecule is very clearly distinct amongst other options for various reasons. One, we know that this market wants a safe, convenient oral option. We've heard that time and time again, going back to the origination of this program at BridgeBio. On top of that, I think we've got the data to say we have a unique proposition in terms of efficacy as well. Primary endpoint result, obviously, very strong. But importantly, I think we've demonstrated kind of first-of-its-kind data against proportionality, which I think is immediately impactful in terms of daily function for these children and will yield increasing benefits over time. But I think importantly, I think that gives hope to the community that this drug actually will be able to finally give something other than just height. And we're looking forward to elaborating on that hope and hopefully delivering against it.
And so should this be approved and launch the low-hanging fruit? is it switches from um the competitors or naive patients yeah so actually this is kind of an
interesting market where there's an incumbent um but they're dramatically under penetration in the us in particular so our job is to both um drive uh drive volume off of injectables because i think there's going to be a lot of demand to get on an oral if you've already gotten on therapy but also we have to expand this market and we know that um the desire to start with an oral is certainly a reason that we are seeing on under penetration in the us and so we really
have to drive both of those okay great and then um we'll wait on price but um unless you wanted
here here it's a little bit easier right i mean there's there's two comps out there that are i I think vasortite is around 400 and change, and the weekly injectable is average around 500. So it's easier comps.
That's a good guidepost on the low end, in my opinion. Okay, very good. Well, thank you so much for taking the time. Thanks for all the updates, and thank you, everyone, for listening.
Thank you all.