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

Good day, everybody. My name is Ash Verma. I cover SMID-Cap biotech and Spec Pharma and welcome to UBS Healthcare Conference. Our next company here BridgeBio Pharma, and I'd just like to quickly introduce our panelists. So Ananth Sridhar; and Anna Wade; and then Chinmay Shukla. So thank you, everybody, for joining us. A lot of different things going on with your story. So maybe I'll just like give an open-ended question and then we can sort of going from there. And just for the audience who are in the room, if you want to submit a question through the QR code, like that will pop up here at this iPad hopefully, and I can bring that in towards the end of the discussion. But with that, yes, maybe just if you can get it started on like the recent 3Q update, and you've had a few different like pipeline readouts come out in the last few weeks, essentially...

Yes. Happy to talk about that. So 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. So 3Q last couple of weeks was 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. So we feel great about that engine. And then we further buttress that engine by reading out 2 Phase III trials, both in very large $1 billion-plus opportunities, ADH1, Encaleret in ADH1 with an expansion opportunity in chronic HP. And then BBP-418 in LGMD2i with an expansion opportunity in LGMD2M, 2U and also Fukuyama disease. So we feel we are very well positioned to transition into becoming a diversified rare disease company. And on top of all of that, we also have an exciting Phase III update coming up in early '26 for infigratinib in achondroplasia. And then later in '26, we'll read out our proof-of-concept study for infigratinib in hypochondroplasia. So 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. So maybe just if we talk about Attruby, the launch has been very successful so far. And the update that you provided in terms of the patient adds in 3Q and seems to be pretty broad-based as well. What I'm trying to understand is where -- like what are the sources of the revenue? Like which type of patients are starting to get on the treatment?

Yes. It's a great question. So 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 U.S., which are prescribing. So 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 have said that our treatment-naive patients have been a majority of them. And I think in the last update, we said that our share is well in the 20s now there, and they comprise of a vast majority of our patients now. So we feel very good about how Attruby is being used by all patients and all physicians. And we are particularly thrilled with the momentum we are seeing in the treatment-naive section of the market.

Yes. 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 like 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?

Yes. Yes, it's a good question. So 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 to 3,000 treatment naive patients who would start therapy every quarter last year. Today, we are seeing it's at least 3,000 patients, but there are probably more than 3,000 patients. So 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 Attruby, especially in the high-volume heart failure clinics section of the market. Beyond that, I think that for Attruby, specifically, we've had very strong clinical data. And really, our commercial strategy has been to lead with our clinical data. So 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. And just as you look towards like 2026, do you think that the focus will continue to be on the naive patients or does that start to diversify a little bit?

Yes. 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 will continue to be the focus. I expect that our switch share has now stabilized. So I think that I don't -- I expect that in '26 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. Yes. I mean one of the things that like I've started to hear from investors just on the impact to VYNDAQEL. So I mean, you might have seen like they missed the VYNDAQEL number a couple of weeks ago when they announced the earnings, which has again kind of stood this controversy, is the market finite? And -- is it like a zero-sum game between the 3 players? So just curious like what -- like when you see that happening, like what does that tell you? Is that a good or a bad sign, I guess?

Yes. I think that maybe there are 2 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? And I think that if you -- again, if you look year-over-year, given that tafamidis has to have an IRA impact this year, right? So 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 that 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 -- 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. So I do think that this is a market where all players are going to do extremely well. But I also think that Attruby is going to be -- we have certainly said that our goal is to be 30% to 40% of the overall market. And internally, given the strong start that they are our partners had in Europe where they're at a majority share, internally, we do try to push ourselves to see that, hey, can we go beyond the 30% to 40% and get a majority share in this market.

Right. And then 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. Does that -- 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?

Yes. So so far, we haven't seen any pricing pressures for us. I think that Attruby is in a very, very privileged position, right? So 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. So 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 is making the choice based on data that we will win a lot of patients and so I do think that we don't expect to see any sort of pressure here. We expect our gross to net to be stable over the next few quarters. So that's kind of what I would say on that topic.

Got it. Got it. Okay. All right. And then just staying on the same theme. So as tafamidis goes generic, yes, 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 like trigger more of a combo use after generic.

So let me first take the combo use questions. Yes, there is combo use in this market. I think it's pretty well known that folks are using 2 agents in combination right now. Very little combo use with Attruby though. Now what is interesting to note is that there were guidelines which were published by the ACC a week or 2 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 TAF IP, 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 a 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 TAF goes generic. You couple that with the product hub 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. And then 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 don't really go down. The growth just maybe slows down a little bit, but the sales definitely don't go down in any way.

Is that because of the volume dynamic or like pricing pressure or any step edit type of...

Yes. So normally, what we have 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. So they don't really -- they also want to be on the most potent molecule. So your volume continues to increase. And I think when it comes to payers, given you have a large installed base of patients, I think at that time, if we give a small rebate, they're not going to require a step edit or something like that. And that's certainly what we've seen in other categories, too. So if your volume continues to accelerate and maybe your price takes a small onetime adjustment, you're going to be able to continue growing through it. And so that's kind of what gives us a lot of confidence here.

Got it. And then 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?

Yes, happy to do that. So 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. And I do think that awareness increasing has driven more diagnosis in the space. So that's one macro comment. The specific data that I would highlight is actually our variant data. So the variant population here is one which has significant unmet need, right? They have a high risk of mortality. Currently, it's a severely underdiagnosed piece of the market, right? So it's a place which the market is going to grow in. If you see what we presented there, we've said that we have -- we're the only agent which has shown a statistically significant difference in mortality and cardiovascular hospitalizations. And I think that at AHA, we continue to expand on that story with a 59% reduction in ECM and a 69% reduction in ACM and first CV event at 30 months. Both of which were stat sig. And 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. And 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. And so the data is now out in a peer-reviewed published manuscript. So very excited about that, I would say.

Great. Awesome. So maybe just like switching gears a little bit, like talk about the pipeline. So you had this -- a few updates, like you said, ADH1 and limb-girdle. Maybe like I'll start with ADH1. So this Phase III update, like can you comment on just the kind of the durability and long-term safety of the normalization effects that happened? Sure. I'll pass it on to Ananth to talk more about ADH1.

Yes, it's a great question. So just to remind folks, we presented top line results from our study of encaleret in patients with autosomal dominant hypocalcemia type 1 ADH1. There's a cohort of about 67 individuals are randomized 2:1 to encaleret versus conventional therapy. What we showed in our primary analysis was 76% of people receiving encaleret normalized their blood and urine calcium by week 24, which is about 6 months of therapy compared to 4% of those same individuals on conventional therapy. So it's a dramatically profound result on the primary endpoint, the co- endpoints of normalization of blood and urine calcium. And then to your question of the durability we've seen from our Phase II cohort evaluating the same criteria that once maintenance doses of encaleret are achieved within about roughly the first month of treatment initiation, the effect seems durable and sustained. And so we've observed that cohort up to 3.5 years now. We published those data this summer, presenting durable effect and importantly, without the need for dose escalation, which we've seen with other products in this field.

So like with this Phase III, like would you have more longer-term follow-up data that will start to...

We will continue to. And what's heartening about our cohort, so more patients discontinue the standard of care arm. The control arm versus none on the encaleret arm. So it was quite well tolerated and the rollover to the long-term extension was nearly complete. So of those who completed the study, 98% of the completers rolled into the long-term extension. So 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.

Yes. And then just on this Phase III, so the hypercalcemia AE, it seems like no discontinuation, but some level of titration that happened. Like does that make you believe that could that be limiting in any way in terms of the efficacy for the molecule? Or like what's sort of happening to try to identify like the right dose at 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 encaleret. These are both commonplace for these patients as they try to identify the right dose. And so I think these are familiar circumstances. Both are -- were asymptomatic and resolved with dose reduction. So they're transient and their response to the dose, they don't require discontinuation. And I think it has no -- it's a sign of treatment effect rather than lack of effect.

Got it. Got it. Yes. I mean with this one, there seems to be a fair bit of debate on just like the market size of the opportunity, right, and like effectively new ICD-10 code. So yes, what's your most like most convincing argument for that this is like a big market size? And -- like do you think that there would be more substantiation of it as you go along in terms of identifying like what -- how many patients are out there that actually need this treatment?

Absolutely. I do think one -- so to just answer your question directly, we think there's about 12,000 carriers of ADH1 in the U.S., so 1 in 25,000 roughly. And 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. So if we think about the broad picture of hypoparathyroidism and the overall prevalence, which I believe is not as highly 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. So I think more to come as well as increased diagnosis rates with awareness of not only our program, but also this condition and access to genetic testing.

Yes. 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. like these are patients that we know who they are. We know the physicians. So I do think that, that's going to be the initial target population for us. And if we just get uptake in those 3,500 patients at a genetic disease price point, right, which is -- 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. But that's kind of what gives us a lot of confidence here is just those 3,500 identified patients by the company.

Yes. And this is something that you're kind of working through like just on this patient identification path while...

Yes. 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, think that they have this disease that they would really like to be on the drug. And so that's also been something which has helped us to continue expanding the number of 3,500 identified patients in the U.S.

Yes. Yes. I think our familiarity with the marketplace and even this last week, 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've learned a cohort of patients at the stone clinic who have positive variances on their calcium-sensing receptor gene. So I think there's 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. So 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. And I know like the pricing strategy can be a little bit custom for this type of a dimension in which like on the hypopara side, there is more like established therapy in sort of crowded market versus this being like a more targeted indication. So what does that -- yes, what's the solution to that effectively?

Yes. I think we will start -- when we launch an ADH1, we will price it like an ADH1 drug. And 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. But at launch, you should expect to see an ADH1 price.

Got it. Okay. All right. I think like Neil threw out this like $300,000 to $500,000 range on the 3Q call. I don't know if that's sort of in the same ZIP code of where you thinking about this or...

Yes, I think what Neil is trying to say is if you look at sort of genetic diseases, on the low end, I would look at things like Crysvita, right? I mean Yorvipath is approved in HP, which is a much bigger indication, and that's priced at about $300,000. But really, the more comparable disease, I would say, are X-linked, Hypophos -- XLH, which is Crysvita, which is about $400,000, Voxzogo, which is also bigger market than this, that's also around $400,000. On the high side, you would look at drugs like Exondys or Varcat, which are -- which can be $750,000 to $1 million. So that's a pretty broad range. But like, yes, that's kind of how we get to that sort of $300,000 to $500,000 range, which $300,000 to $500,000, which Neil was talking about on the call.

Right, right. How much does like the durability of treatment also factor into that dimension, right? Like do you have a sense on like 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?

Yes. I mean, so it opens a question about the -- just the therapeutic hypothesis here. And what we're trying to do with Encaleret is we're trying to restore the wild-type or the native properties of the receptor. And that is what we are showing with the normalization rate. So we're trying to normalize calcium homeostasis, calcium metabolism in these patients. And so that's why we do expect it to be a chronic therapy. And if it's continuing to yield the benefits like we're seeing in our Phase II cohort 2, 3.5 years longer, we certainly expect that patients will continue to persist on that therapy.

Great. Awesome. So back to you, Anna. Thanks for bearing with me. So just on limb-girdle. So yes, here, you've had another positive Phase III. So maybe if you can talk about like the primary secondary outcomes and what are the key data points that you showed?

Yes, absolutely. So yes, BridgeBio had a very exciting week. So we read out 2 positive Phase IIIs. We read out 2 days before announced trial. So this just to take a step back, we're developing BBP-418 for limb-girdle muscular dystrophy type QI. And this trial was an interim analysis, which was originally planning to look at a particular biomarker that is close to the disease, looking at changes in glycosylated alpha-dystroglycan. But we actually saw a really profound effects on clinical outcomes. So this is like the first time, I think, really in the muscular dystrophy space that in a randomized controlled trial, we're seeing not only significant stats sig differences from placebo, but we're also seeing improvements relative to baseline. And so just to go to that in a bit more detail, what we saw was this significant increase in glycosylated alpha-dystroglycan at both 3 months and at 12 months. It was way in excess of what we were expecting to target. So we were hoping to see around a 5% increase in this particular protein to see clinical benefit. We saw 17% increase at 3 months, and then it continued to increase at 12 months. So it ended up being around 24% increase in that protein. Then we saw -- an 80% decrease in serum creatine kinas, which is demonstrating an impact to the site of the muscles, so getting less muscle breakdown. And then the thing that was super exciting is we saw improvements on -- a measure of ambulation and then also a measure of pulmonary function, so forth vital capacity. So the differences we were seeing now were on the ambulation, it was an increase in velocity of 0.14 milliseconds, a difference from placebo of 0.27 milliseconds. That kind of doesn't sound very much, but went over 100 meters that means the patients are walking 14 seconds faster on treatment than on placebo. And then on the SEC, this is like 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 and then we saw a 3% increase in function on drug. So this is like an incredibly strong data set. And this is considering this data set, we're now going to go to the FDA and before the end of the year to discuss whether we -- this data set could support a traditional full approval as opposed to the original strategy, which was an accelerated approval.

Yes, maybe one thing I'll just add is as a scientist it is pretty profound to see that we now have 2 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 Attruby, which is amazing at just halting the progression of the disease. But now we have 2 molecules in Encaleret and BBP-418. Which are reversing the disease, which are approaching towards the cure for the disease. And that's actually very exciting to us from just a scientific perspective.

Yes. Yes. And then just limb-girdle as well, kind of similar vein of question just like what's the most like hard concrete evidence that you have in terms of patient numbers?

Yes, great. And you'll also hear that a lot of the sort of tailwinds are similar in this space than in the ADH1 space. But so essentially, we estimate around 2,500 patients in the U.S. That's based off of prevalence estimate based on we know the carrier frequency of the disease-causing alleles. We also know that there is like an existing patient pool based on like registry data. And then we also had the clinical trial enrolled incredibly fast. So we enrolled 20% over what we were targeting are initially in 8 months early. So there's definitely a lot of unmet need and like patient interest. These patients are typically cared for at sort of MDA clinics. So that's a known entity as well, it's about 150 MDA clinics in the U.S. And 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. And we anticipate that with this being the first disease modifying therapy, hopefully, to come to market there would be an increase in diagnosis similar to what we saw in the SMA space just prior to launch. And then on top of that, what's kind of nice in this space is that there's already sponsored genetic testing. So it's pretty typical than a muscular dystrophy patient once they go to a clinic, they will be put on to sort of expansive muscular dystrophy panel, which includes these genes and so then they get a diagnosis of LGMD2i. And then, I guess, just to speak to something that Chinmay said earlier, there are other expansion indications here. So all the data so far is in LGMD2i but there's also an opportunity in 2U and then Fukuyama Congenital muscular dystrophy.

Got it. Okay. That's great. I have a couple of quick questions from the audience here. So maybe just, I believe this is for ATTR. So just like the under diagnosis of the disease and improving diagnosis has one of -- 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. So 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 to 60,000 patients diagnosed with the disease so far. That means that we are what -- barely a 1/5 fit of the way there. So we are very much in the early innings. And one of the things which we track is number of PYP scans, and you can see that, that continues to increase every year. And then you obviously see the treatment-naive patients and that you can just look at the claims data, that also seems to be increasing every year. So lots of signs which point to the market growing and accelerating. And I think we are very much in the early innings. We're probably around 20% to 25% diagnosed right now.

Got it. Great. And then 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?

Yes. So 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. It's just caused by the deposition of toxic monomers into your heart. And what the depleters are doing is there as the name says, depleting it from the heart. And I think we guys are acting upstream where we are preventing their deposition. So we actually think that they are very complementary. We have an early-stage program developing an ATTR-CM depleter. So we are excited about the opportunity. We don't think it's going to cause like pricing pressure or anything like that. But 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 you for joining us.

Thank you all.