Good day, everybody. My name is Ash Verma, I cover Smith BioTech and SpecPharma, and welcome to UBS Healthcare Conference, our next company here, BridgeBio Pharma. I’d just like to quickly introduce our panelists. Ananth Sridhar, Anna Wade, and then Chinmay Shukla. Thank you, everybody, for joining us. A lot of different things going on with your story. Maybe I’ll just give an open-ended question, and then we can sort of go in from there. Just for the audience who are in the room, if you want to submit a question through the QR code, that’ll pop up here at this iPad, hopefully, and I can bring that in towards the end of the discussion.
With that, yeah, maybe just if you can get us started on the recent 3Q update, and you've had a few different pipeline readouts come out in the last few weeks, essentially.
Yeah, happy to talk about that. First of all, Ash, thank you for hosting us, and thank you to the entire UBS team for giving us an opportunity to participate in the conference, and thank you to the investors who have shown a lot of interest in our story. 3Q, last couple of weeks were really a transformational period for the company. I think we have shown this year that we can really distribute our product commercially in a very competitive market, and we continue to show that in the third quarter earnings call. Our volume accelerated, our price is stable, so our sales have really started to accelerate. We feel great about that engine.
We further buttressed that engine by reading out two phase three trials, both in very large billion-dollar-plus opportunities, ADH1 and Enacalox in ADH1 with an expansion opportunity in chronic HP, and then BBP-418 in LGMD2i with an expansion opportunity in LGMD2M to U and also Fukuyama disease. We feel we are very well positioned to transition into becoming a diversified rare disease company. On top of all of that, we also have an exciting phase three update coming up in early 2026 for infigratinib in achondroplasia, and then later in 2026, we will read out our proof of concept study for infigratinib in hypochondroplasia. A lot happening. I'm happy to dive into all of that, but I think the takeaway is that the company is now transforming itself into being a diversified genetic disease company with multiple big products.
Great. Good start. Maybe just if we talk about Attruby, the launch has been pretty successful so far, and the update that you provided in terms of the patient ads in 3Q, and it seems to be pretty broad-based as well. What I'm trying to understand is what are the sources of the revenue, which type of patients are starting to get on the treatment?
Yeah, it's a great question. Like you said, the uptake has been really broad, both in terms of patients, but also in terms of physicians who are prescribing, regions in the US which are prescribing. That gives us a lot of confidence that this is quite robust and it's going to continue in the future. Having said that, we've always focused most on the treatment naive section of the market or the first line section of the market. We continue to see every single month more treatment naive patients start Attruby than the previous month. Every time we've reported our quarterly number, we've said that our treatment naive patients have been a majority of them. I think in the last update, we said that our share is well in the 20s now there, and they comprise a vast majority of our patients now.
We feel very good about how is being used by all patients and all physicians, and we're particularly thrilled with the momentum we're seeing in the treatment naive section of the market.
Yeah, I hear this from some of the other competitors as well. Just like treatment naive adoption has been very strong. I mean, I'm just curious, what is essentially driving behind that? Is it like a lot of disease awareness and just the availability of the therapy, or is there any—what are some of the pushes that you're doing from a commercial standpoint to get more patients activated?
Yeah, yeah, it's a good question. The market has definitely expanded. If you look year-over-year, the market has expanded meaningfully. We used to say that there are about 2,000-3,000 treatment naive patients who would start therapy every quarter last year. Today, we are saying it's at least 3,000 patients, but there are probably more than 3,000 patients. Number one, the size of the pie has expanded for everyone. That's mainly because of more players coming on the market and more awareness of the disease. That's also activated different types of physicians who are finding these patients, which has really benefited Acoramidis, especially in the high-volume heart failure clinics section of the market. Beyond that, I think that for Attruby's specifically, we've had very strong clinical data, and really our commercial strategy has been to lead with our clinical data.
Whether that's in the AFib population, which is about half of these patients where we have shown the best point estimate, whether it's in the variant subpopulation where, again, we have shown a profound benefit, including a static benefit on mortality and hospitalization, where we continue to publish, including at AHA, more data. I think that those kinds of real-world evidence generation, showcasing Attruby's unique profile, coupled with the market growing, has helped us to really accelerate this launch, I would say.
Got it. As you look towards 2026, do you think that the focus will continue to be on the naive patients, or does that start to diversify a little bit?
Yeah, so we've had a very broad and balanced sort of uptake across all sort of sections of the market, but treatment naive has been the focus. It'll continue to be the focus. I expect that our switch share has now stabilized. I think that I expect that in 2026 and beyond, we're going to continue to see a lot of growth from the treatment naive section, and I think we continue to get our fair share of switches.
Got it. Yeah, I mean, one of the things that I've started to hear from investors just on the impact to Vyndaqel, so I mean, you might have seen they missed their Vyndaqel number a couple of weeks ago when they announced the earnings, which has, again, kind of stirred this controversy. Is the market finite, and is it like a zero-sum game between the three players? Just curious, when you see that happening, what does that tell you? Is that a good or a bad sign, I guess?
Yeah, I think that maybe there are two aspects of this. Maybe I'll break it down into the volume and the price. I think if you look at the commentary from Pfizer, they very clearly talked about double-digit demand growth, right? I think that, again, if you look year-over-year, given that the family has to have an IRA impact this year, right? That means that their volume has to go up by 25% year-over-year just to match the sales number, given the 20% rebate to Medicare. I think that that continues to say that, given they're annualizing at about $4 billion in the U.S., continues to say the market is very large and it continues to grow. I think that stabilizers remain the backbone of care.
Having said that, yes, it is true that we have taken, and again, the company commented on their own earnings call that Attruby has taken share, and we continue to position ourselves as the best stabilizer, the best first-line option for these patients. I do think that this is a market where all players are going to do extremely well. I also think that Attruby is going to be—we have certainly said that our goal is to be 30%-40% of the overall market. Internally, given the strong start that Bayer, our partner, has had in Europe, where they are at a majority share, internally, we do try to push ourselves to see that, hey, can we go beyond the 30%-40% and get a majority share in this market?
Right. I guess just the piece about the Pfizer competitive dynamics, so they have been saying that there would be more pricing pressure on them going forward. Can that translate to more sort of a broader impact on the overall market, or is it something that is singled out just to Vyndaqel?
Yeah, so far, we haven't seen any pricing pressures for us. I think that Attruby is in a very, very privileged position, right? One, we were quite responsible in how we priced, and Neil, our CEO, has commented on this in all of our earnings calls, that we do expect long-term prices in the category have to come down, which is why we started at a 10% discount to Tafamidis, despite having what I would say really strong data on hospitalization, fastest time to separation on hard outcomes, both strong data points that payers care about. I think given that, coupled with the fact that our strategy remains parity access, we're not looking to pay for preferred access. I think if you rewind a few minutes ago, I was saying that the main driver for us has been our clinical data. We want to do that.
We think that if we are all in the physician's office and the physician's making the choice based on data, that we will win a lot of patients. I do think that we don't expect to see any sort of pressure here. We expect our growth to be stable over the next few quarters. That's kind of what I would say on that topic.
Got it. Got it. Okay. All right. Just staying on the same theme, as Tafamidis goes generic, yeah, I'm trying to understand what is your base case assumption. Are you seeing any kind of a combo use right now, and can that trigger more of a combo use after?
Yeah. Let me first take the combo use question. Yes, there is combo use in this market. I think it's pretty well known that folks are using two agents in combination right now. Very little combo use with Attruby, though. What is interesting to note is that there were guidelines which were published by the ACC a week or two ago, which clearly said that there is no discernible benefit of combination therapy. When you couple that with the fact that a combination therapy is about $750,000 a year, and you take your previous question about payers, right, I do think that that segment of the market is at pretty big risk of just going away. Thankfully, we don't play in that segment, so we worry about it less.
As it pertains to your question on Tafamidis, I think that our position on this is very clear, right? We've said that we think that Tafamidis is protected well into the 2030s, potentially up to 2035, given their polymorph patent. I think that when we look at the fact that physicians and payers, physicians and patients are already reaching for Attruby first, right? Well into the 20% range, treatment naive share means that there's a very big section of the market which prefers to use Attruby, which I think further insulates us from whenever Tafamidis goes generic. You couple that with the product hop strategy that they have going on for Vyndaqel right now, all signs point to the fact that this is going to be a very durable market. Lastly, you can look at any kind of commercial analog, right?
Whether you look at the statin place or whether you look at the pH marketplace, when the first-to-market molecule, less potent molecule, goes generic, the second-to-market more potent differentiated molecule, right? We have a differentiated label. The sales of that product do not really go down. The growth just maybe slows down a little bit, but the sales definitely do not go down in any way.
Is that because of the volume dynamic or pricing pressure or any step edit type of?
Yeah. Normally, what we've seen is that volume continues to grow in those categories because ultimately, physicians want to prescribe the most potent molecule, and the drugs are not different in cost for the patients. They also want to be on the most potent molecule. Your volume continues to increase. I think when it comes to payers, given you have a large installed base of patients, I think at that time, if we gave a small rebate, they're not going to require a step edit or something like that. That is certainly what we've seen in other categories too. If your volume continues to accelerate and maybe your price takes a small one-time adjustment, you're going to be able to continue growing through it. That is kind of what gives us a lot of confidence here.
Got it. You had some data that you presented at AHA this past weekend. Maybe if you can just kind of highlight what are the key takeaways from that.
Yeah, happy to do that. We had a lot of data which came out at AHA, and we had, I would say, a very robust engagement with HCPs. Our commercial team was there. They were able to meet with a lot of customers, educate folks on Attruby , and really get the word out. I do think that awareness increasing has driven more diagnosis in the space. That is one macro comment. The specific data that I would highlight is actually our variant data. The variant population here is one which has significant unmet need, right? They have a high risk of mortality. Currently, it is a severely underdiagnosed piece of the market, right? It is a place which the market is going to grow in.
If you see what we presented there, we've said that we're the only agent which has shown a statistically significant difference in mortality and cardiovascular hospitalizations. I think that at AHA, we continue to expand on that story with a 59% reduction in ACM and a 69% reduction in ACM and first CV event at 30 months, both of which were stat-sig. I think that what was really profound to me as a scientist is sometimes you'll see these poster presentations, and then you don't see a peer-reviewed publication. Maybe it's because I went to grad school and suffered through a lot of peer review. I think your smile tells me you did too. I think that what was very exciting to me is we had a simultaneous publication also. The data is now out in a peer-reviewed published manuscript.
Very excited about that, I would say.
Great. Awesome. Maybe just switching gears a little bit, talk about the pipeline. You had a few updates, like you said, ADH1 and Limgardel. Maybe I'll start with ADH1. This phase three update, can you comment on just the kind of durability and long-term safety of the normalization effects that happened?
Sure. I'll pass it on to Ananth to talk more about ADH1.
Yeah, it's a great question. Just to remind folks, we presented top-line results from our study of Encaloret in patients with autosomal dominant hypocalcemia type 1, ADH1. There's a cohort of about 67 individuals that were randomized 2 to 1 to Encaloret versus conventional therapy. What we showed in our primary analysis was 76% of people receiving Encaloret normalized their blood and urine calcium by week 24, which is about six months of therapy, compared to 4% of those same individuals on conventional therapy. It was a dramatically profound result on the primary endpoint of the co-endpoints of normalization of blood and urine calcium. To your question of the durability, we've seen from our phase two cohort evaluating the same criteria that once maintenance doses of Encaloret are achieved within about roughly the first month of treatment initiation, the effect seems durable and sustained.
We have observed that cohort up to three and a half years now. We published those data this summer, presenting durable effect, and importantly, without the need for dose escalation, which we have seen with other products in this field.
With this phase three, would you have more longer-term follow-up data that will start to?
We will continue to. What's heartening about our cohorts are more patients discontinue the standard of care arm, the control arm, versus none on the Encalox arm. It was quite well tolerated, and the rollover to the long-term extension was nearly complete. Of those who completed the study, 98% of the completers rolled into the long-term extension. We will have a rich data set to evaluate for long-term data, both on durability, safety, as well as some of the long-term effects on kidney and bone health.
Yeah. And then just on this phase three, the hypercalcemia A, it seems like no discontinuation, but some level of titration that happened. Does that make you believe that could that be limiting in any way in terms of the efficacy for the molecule, or what is sort of happening to try to identify the right dose and the right?
I think you got it right on, which is that early in the titration, there may be excursions in blood calcium, whether it's low or high, depending on the individualized dose needs for that patient. We saw one SAE that was related to conventional therapy due to hypercalcemia, one on Encalox. These are both commonplace for these patients as they try to identify the right dose. I think these are familiar circumstances. Both were asymptomatic and resolved with dose reduction. They're transient and they're responsive to dose. They don't require discontinuation. I think it's a sign of treatment effect rather than lack of effect.
Got it. Got it. Yeah. I mean, with this one, there seems to be a fair bit of debate on just the market size of the opportunity, right, and effectively new ICD-10 code. Yeah, what's your most convincing argument for that this is a big market size? Do you think that there would be more substantiation of it as you go along in terms of identifying how many patients are out there that actually need this treatment?
Absolutely. I do think, to just answer your question directly, we think there's about 12,000 carriers of ADH1 in the U.S., so one in 25,000, roughly. Of those 12,000, we think the diagnosis rate is somewhere in the 20s, 20% today. There's a coalescence of data that we can look at to get there, which is a mix of ICD-10 coding data, a mix of individuals involved in our clinical program, as well as our disease monitoring study, as well as with our genetic testing program, which has yielded a meaningful amount of positive tests for ADH1. The other element that I would point folks to just from published literature, we presented on our sponsored testing program, ADH1 is the most common isolated genetic cause of hypoparathyroidism.
If we think about the broad picture of hypoparathyroidism and the overall prevalence, which I believe is not as hotly debated, and we see that ADH1 is the most common genetic cause, it's kind of hard to decouple the fact that ADH1 may actually have a prevalence similar to what we've seen in the large genetic population data sets. I think more to come, and as well as increased diagnosis rates with awareness of not only our program, but also this condition and access to genetic testing.
Yeah. Maybe I'll just add to what Ananth said, right? I think between the ICD-10 code, the sponsored genetic testing programs, as well as the various folks enrolled in our trials and their family members, we've identified 3,500 patients in the U.S. These are patients who we know who they are. We know the physicians. I do think that that's going to be the initial target population for us. If we just get uptake in those 3,500 patients at a genetic disease price point, right, which can be a meaningful market opportunity of over $1 billion just in the U.S. Beyond that, there's a European opportunity. Beyond that, there's an opportunity to drive diagnosis and further increase sales in ADH1. That's kind of what gives us a lot of confidence here is just those 3,500 identified patients by the company. Yeah.
This is something that you're kind of working through just on this patient identification path while pursuing the?
Yeah. I also think what's interesting to me is it's only been a couple of weeks since we announced our data, and we've already had families as well as physicians come inbound to us saying that they have this disease that they would really like to be on the drug. That has also been something which has helped us to continue expanding the number of 3,500 identified patients in the U.S.
Yes. Yeah. I think our familiarity with the marketplace, and even this last week, there is Kidney Week at the American Society of Nephrology. There were cases presented on ADH1, as well as providers who mentioned that while we know a lot of the patients today are cared for and diagnosed in endocrinology clinics, they may present in stone clinics as well under nephrologist care. We have learned of a cohort of patients at a stone clinic who had positive variants on their calcium sensing receptor gene. I think there is certainly room to not only grow our familiarity with where these patients are, but grow the diagnosis rate amongst those who have signs and symptoms as well.
Got it. Okay. I think this is kind of a unique dynamic that you have that you're also pursuing for a hypopara indication with the same molecule. I know the pricing strategy can be a little bit custom for this type of dimension in which on the hypopara side, there is more established therapy in sort of crowded market versus this being a more targeted indication. What does that, yeah, what's the solution to that effectively?
Yeah. I think we will start when we launch an ADH1, we will price it like an ADH1 drug. I think that as we generate data in chronic HP, which we are very excited about, once we have that data and once we are serving the chronic HP population, we can talk about thinking about the price a little differently. At launch, you should expect to see an ADH1 price.
Got it. Okay. All right. I think Neil threw out this 300-500K range on the 3Q call. I don't know if that's sort of in the same zip code of where you're talking about this or?
Yeah. I think what Neil was trying to say is if you look at sort of genetic diseases, on the low end, I would look at things like Crysvita. I mean, Yarmouth Path is approved in HP, which is a much bigger indication, and that's priced at about $300,000. I mean, the more comparable disease, I would say, are XLH, which is Crysvita, is about $400,000, Voxzogo. There's also a bigger market than this. That's also around $400,000. On the high side, you would look at drugs like Exondys or Viltolarsen, which can be $750,000-$1,000,000. That's a pretty broad range. Yeah, that's kind of how we get to that sort of $300,000-$500,000 range, which Neil was talking about on the call.
Right. Right. How much does the durability of treatment also factor into that dimension, right? Do you have a sense on is this going to be chronic?
We do think this is going to be chronic, but Ananth, do you want to talk about some of the long-term data which you guys already have?
Yeah. I mean, it opens the question about just the therapeutic hypothesis here. What we're trying to do with Encaloret is we're trying to restore the wild type or the native properties of the receptor. That is what we were showing with the normalization rate. We're trying to normalize calcium homeostasis, calcium metabolism in these patients. That is why we do expect it to be a chronic therapy. If it's continuing to yield the benefits like we're seeing in our phase two cohort, three and a half years longer, we certainly expect that patients will continue to persist on that therapy.
Great. Awesome. Back to you, Anna. Thanks for bearing with me. Just on LGMD2i, yeah, here you've had another positive phase three. Maybe if you can talk about the primary, secondary outcomes and what are the key data points that you showed.
Yeah, absolutely. Yeah, BridgeBio had a very exciting week. We read out two positive phase threes. We read out two days before Ananth's trial. Just to take a step back, we're developing BBP-418 for limb-girdle muscular dystrophy type 2I. This trial was an interim analysis, which was originally planning to look at a particular biomarker that is causative of disease, looking at changes in glycosylated alpha-dystroglycan. We actually saw really profound effects on clinical outcomes. This is the first time, I think, really in the muscular dystrophy space that in a randomized controlled trial, we're seeing not only different significant SATSIG differences from placebo, but we're also seeing improvements relative to baseline. Just to go into that in a bit more detail, what we saw was this statistically significant increase in glycosylated alpha-dystroglycan at both three months and at 12 months.
It was way in excess of what we were expecting to target. We were hoping to see around a 5% increase in this particular protein to see clinical benefit. We saw a 17% increase at three months, and it continued to increase at 12 months. It ended up being around a 24% increase in that protein. We saw an 80% decrease in serum creatine kinase, which is demonstrating an impact to the site of the muscle. You are getting less muscle breakdown. The thing that was super exciting is we saw improvements on a measure of ambulation and also a measure of pulmonary function, so forced vital capacity. The differences we were seeing there were on the ambulation, it was an increase in velocity of 0.14 meters per second, a difference from placebo of 0.27 meters per second.
That kind of doesn't sound very much, but over 100 meters, that means that patients are walking 14 seconds faster on treatment than on placebo. On the FEC, this is an endpoint that's been used to approve other drugs. It's very well known. What we saw there was a 2% decline in the placebo group, which is consistent with natural histories. We saw a 3% increase in function on drug. This was an incredibly strong data set. Considering this data set, we're now going to go to the FDA before the end of the year to discuss whether this data set could support a traditional full approval as opposed to the original strategy, which was an accelerated approval.
Yeah. Maybe one thing I'll just add is, as a scientist, it is pretty profound to see that we now have two molecules. Normally, when you make a drug, you're trying to slow the progression of a disease. Once in a while, you get a drug like Acoramidis, which is amazing at just halting the progression of the disease. Now, we have two molecules in Enacalox and BBP-418, which are reversing the disease, which are approaching towards a cure for the disease. That is actually very exciting to us from just a scientific perspective.
Yeah. Yeah. And then, just on LGMD2i as well, kind of similar vein of question, just what's the most hard concrete evidence that you have in terms of patient numbers?
Yeah. Great. You'll also hear that a lot of the sort of tailwinds are similar in this space than in the ADH1 space. Essentially, we estimate around 2,500 patients in the U.S.. That's based off of a prevalence estimate based on we know the carrier frequency of the disease-causing alleles. We also know that there is an existing patient pool based on registry data. We also had the clinical trial enrolled incredibly fast. We enrolled 20% over what we were targeting initially and eight months early. There's definitely a lot of unmet need and patient interest. These patients are typically cared for at sort of MDA clinics. That's a known entity as well. There's about 150 MDA clinics in the U.S.. A lot of these patients are currently cared for in those clinics.
We do know that there's probably some patients that know they have some kind of muscular dystrophy that are not currently genetically diagnosed. We anticipate that with this being the first disease-modifying therapy, hopefully to come tomorrow, there would be an increase in diagnosis similar to what we saw in the SMA space just prior to launch. On top of that, what's kind of nice in this space is that there's already sponsored genetic testing. It is pretty typical that a muscular dystrophy patient, once they go into a clinic, will be put onto a sort of expansive muscular dystrophy panel, which includes these genes. Then they get a diagnosis of LGMD2i. I guess just to speak to something that Chinmay said earlier, there are other expansion indications here.
All the data so far is in LGMD2i, but there's also an opportunity in Fukuyama congenital muscular dystrophy.
Got it. Okay. That's great. Thank you so much for that. I have a couple of quick questions from the audience here. Maybe just I believe this is for ATTR. Just like the underdiagnosis of the disease and improving diagnosis has been one of the key growth drivers, where do you think we are in terms of penetration of the diagnosis?
That's a great question. I think that we are very much still in the early innings. Maybe taking a big step back, I think that the prevalence of ATTR-CM in the U.S. is probably around 250,000 at least. I think that there have been probably 50,000-60,000 patients diagnosed with the disease so far. That means that we are what, barely a fifth of the way there. We are very much in the early innings. One of the things which we track is number of PYP scans. You can see that that continues to increase every year. You obviously see the treatment naive patients in that you can just look at the claims data. That also seems to be increasing every year. Lots of signs which point to the market growing and accelerating.
I think we are very much in the early innings. We're probably around 20%-25% diagnosed right now.
Got it. Great. One last question here. How do you think the depleters fit into the therapy if they come to the market? Does having a disease-modifying therapy put more pricing pressure on the current stabilizer and silencers?
Yeah. We're excited about depleters. I think we are going to see what data they show. The depleters are not really in competition, at least with the stabilizers, because if you think about this disease, this is a mass action disease which is caused by the deposition of toxic monomers into your heart. What the depleters are doing is they're, as the name says, depleting it from the heart. I think we are acting upstream where we are preventing the deposition. We actually think that they are very complementary. We have an early stage program in developing an ATTR-CM depleter. We are excited about the opportunity. We do not think it is going to cause pricing pressure or anything like that.
We do think it's going to allow us an opportunity to further serve this patient population and to further reduce the mortality and morbidity associated with the condition.
Great. With that, we can wrap it up. Thank you so much for this.
Thank you, Ash. Thank you to all of you for joining us.
Thank you.