Okay. Well, we're going to get started with our next session. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies. Thanks for joining me today. It's my pleasure to have the BridgeBio team with me. To my direct left is Tom Trimarchi, CFO, and to his left, Ananth Sridhar, CEO of Endocrine Disorders. Welcome, both of you.
Thanks for having us. It's great to be back in New York, sun's shining.
Yes
Knicks are in the finals, and we're at Jefferies. What more can you ask for?
Great. Those in the audience less familiar with the BridgeBio 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, milestones over the next 6-12 months would be very helpful.
Yeah, of course. BridgeBio Pharma is a company that's about 10 years old now. We were really built to deliver patient impact at scale, specifically focusing on patients with genetic diseases. 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 Attruby, which is about a year into the launch, and it's really still ramping. We're annualizing about $720 million in the sales in the U.S., and also have seen strong uptake ex-U.S. with our partner Bayer . That's, I think, the first leg of the stool or chair.
Right behind that, we've got three products that are now on the other side of really remarkable phase III data sets that we're focused on submitting to the FDA and global regulatory authorities and will be launching starting at the end of this year. That's one in limb-girdle muscular dystrophy Type 2I/R9 ( BBP-418). We see this as a huge unmet need. It'll be first drug to that market, clear $1 billion TAM for us. Right behind that, we have encaleret for hypoparathyroidism, with our first indication being a genetic subtype called ADH1. Ananth is here with me, hopefully we can spend a good amount of time on that.
Third will be infigratinib. That's a small molecule oral FGFR3 inhibitor for FGFR3-related skeletal dysplasias, starting with achondroplasia with an expansion into hypochondroplasia. That's a multibillion-dollar opportunity for us, clearly. Lot to be excited about. Yeah, I think the next 12 months are going to be focused on execution, where we can keep rolling on Attruby, keep seeing strong uptake, importantly in the first line treatment-naive setting. 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. Maybe starting with Attruby, it's doing very well. You're capturing, like you mentioned, a lot of first-line market share. I think it was above 25%.
That's right.
most recently.
That's right.
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. What's resonating with doctors and so forth?
Yeah. It's a great question. I would say going back to the design of the molecule, we made Attruby 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? We engineered this compound to be maximally potent against stabilization, right? We're a 90%-plus stabilizer, near complete stabilizer per our label. That is the foundational scientific differentiation of this compound. 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 III study where we saw market leading efficacy, our key marketing messages are 3-42-50.
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. 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.
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 Attruby, you already believe it's differentiated. 25% and growing in the first line setting, one in four patients are getting this because their physician believes it is the best drug for them and it's differentiated.
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 3-42-50. 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. To give physicians a little bit more of a contemporaneous apples to apples comparison against tafamidis, which I think is going to stack up favorably as the clinical trial data have as well.
Great. That makes a lot of sense. Q1, you did about $180 million, fifth quarter, a full launch. That's up from $145 million. When I look at the trajectory, it's linear. It's quite amazing to see it's not decelerating. First, it's kind of a narrow-minded question, but Q2, how does volume look? The weekly patient adds, is it consistent? Second part of that would be, Q1, there's technically seasonality, and yet you were able to manage to get sales to grow linearly. Wouldn't Q2 accelerate on gross net improvement, for instance?
Yeah, that's a great question. Maybe let me start on the second part of the question, and I'll weave into my answer, hitting the first part as well. The point about seasonality in Q1, I understand that basically you're saying if there's a structural headwind in the funnel in Q1, shouldn't that be a big boost as you look sequentially to Q2? We didn't see any seasonality. We didn't see anything in the funnel that suggested an unusually poor conversion from demand to sales. That was pretty consistent with what we've seen in the quarters leading up to it. I wouldn't expect that headwind to tailwind dynamic Q1 to Q2. What we are seeing, which we're happy to see, is a steady and consistent improvement in 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, two, a market that continues to expand. On the first part, we talked about the reasons why, right? I think increasingly physicians are seeing Attruby as the right option, they're getting more and more familiar with how to use it, how to get it, all of that, we've made it very easy to do all of that. That's driving share. The market is continuing to expand. This time last year, I'd have told you we think there's probably 2,000 to 3,000 treatment-naive patients coming to the bottom of the funnel every quarter. That looks more like 3,000 to 4,000 now, we don't see any signs of slowing on that front. I think that's how I'd put it.
Understood. Momentum seems strong. You'll generate some more real-world evidence to further solidify your positioning. I think at one point, correct me if I'm wrong, you've kind of mentioned. "Wall Street's never wrong.". I could be wrong, but you mentioned maybe we get 30% peak market share. You're already at 25%, why couldn't this be 50%? Is this just a very conservative statement from you guys?
Look, we're a bunch of former scientists or current scientists at this company, we're very data-oriented. The 30%-40% comes from market research we've done. 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%-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. When we're in that range, hopefully soon, above 30%, maybe that's time to think, "Okay, where could this go? What's the upside here?
Okay. Maybe two more, it's more investor-related questions before we move on to the pipeline. I just have to ask, there's generic Vyndaqel that could be available 2028. I think it's one filer. Generic Vyndamax, I think there's three that Pfizer settled for mid-2031. The question is, if generics can enter, why is there not a price vortex? Why is there no volume change affecting Attruby 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. 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 tafamidis. Our hope is that when that eventually does happen in mid-2031, but really the theoretical pressure would come in 2032, 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 Attruby. There's going to be a health economic argument there too.
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. That's the most important thing we will do. No change in strategy as a result of the dynamics around the other products in the class. I think 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 androgen receptor inhibitors with Xtandi and Zytiga. We've seen it in PAH. We've seen it in a lot of different categories.
Thank you. 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 CARDIO-TTRansform data coming up in second half 2026. It is my understanding a proportion of patients could be on combo with tafamidis plus Ionis. If that succeeded, how should we think about that? Because there are no Ionis plus Attruby patients in that study. my understanding. Investors feel a little bit, they don't know how to think about it. What's your view about that?
Yeah. First, this is a large, well-powered study in our minds. We think it's going to be successful, and we think it'll probably hit in all of the important subgroups. Just in terms of 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. They already increasingly are reaching for Attruby with that in mind.
Really, we're talking about instead of Attruby monotherapy and Attruby plus a knockdown, and if the doctor thinks that's appropriate for the patient, I think that's fine with us. Interestingly, 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 tafamidis as the stabilizer in that combination. I think continue to hammer the differentiation messages that serve us well in monotherapy frontline will also help us if the market trends towards more combination use as well.
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. Like Tom is suggesting, really capturing frontline share remains our priority and will continue to be that case regardless of the outcome of the study.
Yep. Exactly.
Regardless, congratulations on the strong execution. More to come. Shifting gears, Ananth, to you then on ADH1 and encaleret. I think the NDA, remind me, was it submitted in May?
That's right.
Okay. You should get some kind of acceptance July. 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 III.
My understanding, there are no drugs approved for this indication, ADH1. Remind us the prevalence, and in the U.S., what % of those patients are diagnosed, identified, ready to go by the time you launch?
It's a great question. If we look at the general population genetics databases, 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. That approximates to about 10,000 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 2025. That would approximate about one in five, one in six have been diagnosed. 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 2025 alone in the ICD claims, is about 70 new patients are being claimed a month on average. It's a fairly linear trend, at least, that we saw last year, and we'll continue to monitor how that evolves this year.
Have you, at Bridge, found all these patients with the ICD-10 codes, to be clear? Do you know where they are?
Yes. When we have access to these ICD-10 data sets, we are able to see institutions down to the NPI level of where patients are being claimed.
Oh, go ahead.
I would just say, 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 Ananth, are out in the field doing that, obviously in a compliant way today. We'll continue doing that over the next year plus.
Okay. 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. 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. Single high digit thousands is the price point that payers would manage the drug to label. Wherever that would index us is products like Crysvita, Skyclarys, Truseltiq. 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. Even within the 2,000 diagnosed patient pool, that's a big number on that kind of price point. Okay.
Should you be approved, let's call it January of 2027, when do you exactly launch specifically? Why wouldn't there be a bolus, or are you expecting a bolus?
We would be prepared and intend to launch soon after PDUFA date, similar to our dynamics with the Attruby. We've developed the muscle power and the infrastructure and the systems to support that cadence of launch, and certainly something we intend to continue. In terms of just 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. That translates more into every four or five months, every six months, sometimes, depending on people's lives. 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. As we think about, the beauty here is each of your products have life cycle management opportunities. You're starting a hypo-PTH as a phase III study in the summer-
That's right.
of 2026. Remind us how long it took you to do the ADH1 study from start to finish, and could it be a similar timeframe for hypo-PTH?
Yeah. That's a great segue. We are intending to launch our RECLAIM-HP phase III study of encaleret and chronic hypoparathyroidism this summer, so in the coming months. In terms of the cadence of the study, 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. We believe that there is an opportunity to have a rapid enrollment curve with a six-month study. Life cycle 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.
At the end of the day, for hypo-PTH, is it your guys' 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, and the primary endpoint to assess the response rate to encaleret. 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. It's something that's currently not reflected on labels for replacement hormone and something that we think can not only differentiate encaleret 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 III. In our phase II sentinel study, we saw 80% of individuals not only normalize urine calcium but also blood calcium.
There is an opportunity to demonstrate differentiated benefit on both metrics, and we're excited to evaluate our drug on that basis.
I think in the post-surgical population, if we can replicate or even come close to what we've seen already in phase II, that'd be differentiating alone. It'd be an oral option in what is going to be a very large market where 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. There's a big unmet need there, right? These are patients that I don't really know that PTH replacement makes a lot of sense, so basically, untapped market opportunity for us to own. On top of, by then, ADH1 hopefully will be in the early days, but well ramped up and in key part of clinical practice.
Okay, great. Moving on to LGMD, which actually could be approved later this year. Before I forget, all three of these programs, my understanding, you get a PRV voucher if they're approved, or?
We will get one for limb-girdle. We don't expect to get one for encaleret, just given we have a pediatric study ongoing, but its first approval will be in adults. For infigratinib, we may get one as well.
Okay, great. LGMD2I, again, another strong data set. I think you've mentioned the patient prevalence is around 7,000 in the U.S. and E.U. What % of that 7,000 is actually in the U.S., and by the time you're approved, what kind of line of sight do you have in terms of number of patients you've found?
Yeah, good question. 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 2,000-3,000 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. Huge urgency to treat here, I think, is what we'll see.
I think the thing that we need to do for the next couple of 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. Until now, there's not really been a need to.
Genotype-
Determine that it's a 2I versus any of the many other types of limb-girdle muscular dystrophy. I would say the plus here is fairly concentrated site of care in the U.S. At least there's around 166 MDA centers, where about half the patient receive care. In those centers, testing is much more prevalent already. 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. Here, the patient prevalence seems like it's even more rare than ADH1. Going back to pricing power, is this kind of a DMD exon skipping type of pricing, which is like $1 million?
I wouldn't put an exact number on it, we see here the bookends are something like Crysvita 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 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.
Importantly, and I think some people miss this, for patients that randomized to BBP-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. Really amazing outcome. We're hopeful that in our discussions with payers that we'll be able to price this well.
Right. The same compound is going after 2U, 2M, Fukuyama, I think. Are those next trials going to be phase IIIs, straight to phase IIIs?
2U, 2M, as well as expansion into a broader pediatric population will happen starting now. Basically, those will be label-enabling studies. Fukuyama, really interesting Japan-centric opportunity. There's about 2,000 patients in Japan. That will need probably a little bit more work with the regulators to determine the exact registration path. We're working on that right now as well.
Okay, great. The last couple minutes, achondroplasia. I think, is the NDA filing in Q3 of this year or-
Second half, yeah.
Second half. I guess you're unique here relative to the competitors, not only being oral, but with great data, but I think you're the only one at breakthrough designation. Are you expecting a priority review, and is there going to be 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, that's interesting as well in terms of liquidity. I think you're right. 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, importantly, I think we've demonstrated 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.
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. We're looking forward to elaborating on that hope and hopefully delivering against it.
Should this be approved and on launch, the low-hanging fruit is it switches from the competitors or naive patients?
Yeah. Actually, this is kind of an interesting market where there's an incumbent, but they're dramatically under-penetrated in the U.S. in particular. Our job is to both 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. Also, we have to expand this market, and we know that the desire to start with an oral is certainly a reason that we are seeing under-penetration in the U.S. We really have to drive both of those.
Okay, great. We'll wait on price, but unless you wanted to make.
Here, it's a little bit easier, right? There's two comps out there that are, I think Voxzogo is around $400 and change, and the weekly injectable is average around $500. It's easier comps.
Understood. 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.
Thanks, Andrew.
Thank you, Andrew.