Well, good afternoon, everyone. Thanks for joining us here after the lunch session. Get right back into the fireside discussions. My name's Derek Archila. I'm one of the Biotech Analysts here at Wells Fargo. Really excited to have next here, BridgeBio. From the company, we have Chinmay Shukla, Chief Business Officer, congratulations on that, as well as Anna Wade, COO of the Neuromuscular Division. So thank you guys for joining us.
Derek, thank you for hosting us, and thanks to the investors for joining us. We are excited to speak to you today and excited for all our conversations.
Excellent. Well, Chinmay, maybe just to level set us with the business and where you guys are. We've got a pretty solid growing base business with Attruby, three launches upcoming. So maybe just give us a state of the business before we dig in.
Yeah. It's a great question. So state of the business today is, if you look at our post phase III drugs, right, that's in ADH1, limb-girdle, ATTR-CM, obviously, and achondroplasia. We have $8 billion of de-risked peak year sales potential. Total, if you look in the entire pipeline, we have $10 billion of risk-adjusted sales potential. So if you feel great about that, I think if you look at Attruby second quarter global revenues were annualizing to over $1 billion. U.S. revenues were $222 million. We've been growing very nicely at about $25 million- $30 million quarter-over-quarter. We expect to keep growing at that $25 million- $30 million quarter-over-quarter cadence for Attruby. I think all the clinical updates on Attruby have been extremely positive.
We can get into that more and that gives me a lot of confidence that in 2027, as we launch these next three drugs, that is going to add a lot of growth. Then eventually, second half 2027, once these clinical messages take hold in the community, Attruby is also going to start to accelerate. We feel very good about where we are. The last thing which I will say, which is important in the long-term perspective of the business is, for us, as we start to have all these revenues and generate cash flow, we think about where can we invest it. If you look at the genetic disease landscape, innovation has never been higher, unmet need has never been higher.
Yes, of course, we have to grow into all of that, and we have to do it in the right way, but we feel like we have the opportunity to help a lot of patients, and that, I think, will accrue to the benefit of our shareholders.
Excellent. Well, maybe let us start with Attruby. You provided some good context there in terms of growth and things. But we just came out from ESC. We had the CARDIO-TTRansform data and all that stuff. I guess what is your view in terms of how the market continues to evolve and the role of stabilizers?
Yeah. There has been a lot of clinical updates in the TTR space, and so let me sort of summarize where I think we are at right now and where we see this market growing. First of all, stabilizers post CARDIO-TTRansform, it is very clear that today, as well as in the future, almost all new frontline ATTR-CM patients will start on a stabilizer. Today, that number is north of 80%. I do not think that that is going to change given what we saw in CARDIO-TTRansform. I also think that combination therapy is not really effective, and it is not going to be a big part of this market going forward. That is the second thing which we learned.
The third thing which we learned is the two knockdowns are very similar to each other, and that obviously feeds into why stabilizers are frontline, but if you look at the placebo-adjusted knockdowns, they are the same. If you look at the hazard ratio on monotherapy, they are the same. Then the last thing, which I think ESC told us, which I think is a little lost sometimes from investors, is there is meaningful room to help beyond VYNDAMAX. Obviously today, a ton of patients, majority of frontline patients start on VYNDAMAX, which makes sense given it is the established product. But we think Attruby as the next gen, second generation differentiated stabilizer, will take more and more share, and more patients will start on that drug because simply put, it is a better drug.
I think that we feel very good about where we are, whether it is because if you look at subpopulations like AFib variant, whether you look at unique nephroprotective effects of Attruby, and now what you are starting to see, which is really interesting, is real-world evidence start to come to the front, right? You have had one publication. We have heard talks about there being more independent real-world studies which are coming out, so we have to see what happens at HFSA and AHA. But I think all of that will mean that stabilizers will continue to be the frontline therapy of choice. Then over time, we do expect Attruby to keep taking more and more share and become the preferred stabilizer.
You talked about some of these data sets that are coming, whether they are yours or externally. What other evidence do you want to generate between now and maybe the tafamidis patent expiry to really drive home what you are talking about in terms of that differentiation?
Yeah. All of our work on this front stems from what physicians tell us is most convincing to them. What we have learned is, number one, subgroup data, right? So that is why this AFib data really drove AFib and variant subgroup data, which showed that Attruby confers a very large benefit amongst the AFib population and has the highest point estimate in the variant subpopulation. Actually, it has a stat sig benefit on variants, which is really remarkable if you think about it, given the low number of patients in that segment in the trials, right? I think that that is convincing. I think we have now built on that with this very unique nephroprotective effect that Attruby has. That is still in its early days right now. I do not think that that message has fully gone out to the community.
We just published a paper on it a couple of months ago. I think it's going to take six to nine months for people to fully appreciate just how profound that nephroprotective effect is that Attruby confers. I think the third thing which we've heard from physicians is real-world evidence. Of course, the most convincing real-world evidence is when it's not published by us.
So far, there have been, I think, three studies to my understanding. One we've been involved with, the other two we haven't been involved with. Even in studies where we are not involved, you are seeing that acoramidis outperforms tafamidis in real-world settings. We hear that there is going to be a big publication at HFSA on real-world evidence, which I think will further move the field in terms of understanding how to use these drugs in the real-world setting. Those are the kinds of things which I think are going to be important. I think our job right now is to educate physicians on all these benefits which have already been generated.
I think the other factor which we don't need to educate physicians on, but which maybe we need to do a better job educating Wall Street on is things like channel dynamics, which mean that even in 2031, when VYNDAMAX does eventually go generic, because this is a channel controlled by specialty pharmacies, institutional specialty pharmacies, as opposed to payers, we do think that volume for Attruby is going to remain high. I actually think if you look at drugs like this, and we updated our corporate decks, we have some examples there now. If you look at these kinds of situations, you always see that the second-gen differentiated product continues to grow after the first-gen product has a loss of exclusivity. I also know that some of your own work suggests that.
It is true.
I think you can also help us with that.
Well, I was going to say also, when you think about the dynamics and some of this came out at ESC in terms of we're treating these patients earlier. I always feel like there's this, maybe this is a wrong way to think about it, but after 2031, generic tafamidis comes, and then Attruby goes off a cliff. But the fact of the matter is, if you're putting patients on in 2029, 2030, they're probably going to be on drug for four to five years, and the payers are not really going to make you switch a patient that's doing well, right? So, you have that maybe at least giving you that revenue tail, and then it's up to you in terms of, again, talking about those channel dynamics in terms of just even keeping the volume increasing, maybe slower, but you're still growing.
Yeah, I agree with you.
Yeah. See, we've done our homework. But yeah, I guess when.
Well, you've done a lot of work on this
Yeah.
I know you're up to date on it.
When we think about TTR in general, I guess, were there any other takeaways from ESC in terms of where you think the field's going, just from an overall perspective in terms of the diagnosis rate and the growth? Because you've got a lot of tailwinds, just in that sense as well.
That's a very good point. And actually, if I think about the two biggest tailwinds for Attruby, one of them is the fact that the frontline market continues to grow.
Before we launched in 2024, we were saying that there are about 8,000- 12,000 new patients, frontline patients who start an ATTR-CM therapy every year in the U.S. I think about six to nine months ago, we updated that to say that there are, call it, 12,000- 16,000 patients. I think now what we are seeing is that there are at least 16,000 patients. If you see, you've gone from 8,000 to 16,000 over a period of two years, and it's still growing, right? Our share in that market is also growing. That is a big tailwind. Nothing at ESC, everything at ESC reinforced that. The more awareness about ATTR-CM, the more patients people find with this disease.
I actually feel every time we have these big conferences where there's a lot of focus on this disease, it helps a lot with diagnosis. It helps a lot with awareness. That is definitely a big tailwind for us. I actually think that that tailwind, coupled with the differentiation, and slow gains and share are the two reasons why, despite the fact that we have some headwinds, such as the second-line pool normalizing, such as Pfizer rebating, we are able to keep growing consistently. That is why, if you saw last quarter, we had nice growth quarter-over-quarter, and if you look next few quarters, we expect that to keep going.
Got you. Not to put you on the spot, but in terms of stabilizer uses in the frontline, I guess, Alnylam will say they're growing, you guys are saying you're growing. Is Pfizer not growing? Or is everyone growing? How are the share dynamics going? I guess, where do you guys think you'll be? Because I think one of the things that you guys had said in the past was your assumption was it was going to be a four-player market and what your share was going to be. Will you update some of those estimates?
Yeah, great. I'll take that in the reverse order. Yeah, we have said before that we expect at peak Attruby to get 30%-40% share. We are doing more market research now, and we will update it. I will say that that is at peak. I do think, as I mentioned, it's going to take a year or so for these messages to truly get understood by the community. So I do think for the next few quarters, we will keep growing by that $25 million-$30 million quarter- over- quarter sales absolute number that we have said before.
I do think we will update that 30%-40% peak share number. Does it go 35%-45%, 35%-40%? Wait to see that. I will not create that much news right now. The second thing which I would say is, how are the frontline dynamics evolving? This is a stabilizer-first market, right? More than 80% of frontline patients, by our calculation, start on a stabilizer. That number is not really changing. Really what's changing is a majority of patients today start on VYNDAMAX.
Little by little, I think we're making inroads such that we are getting a little more share, right? If you think about it, let's try to make it very rough. If more than 80% are on a stabilizer, that means less than 20% are on a knockdown. Most of that is obviously going to AMVUTTRA. Of the remaining 80%, if I say half of the stabilizer patients, more than that are on VYNDAMAX, that means 55% or so, 60% are starting on VYNDAMAX. We have said our own share is north of 25% and growing slowly. That is how that is evolving.
Mm-hmm. Excellent. Maybe we shift gears to the pipeline because there's so much to talk about, but I think Attruby seems like growing base business, durable, and more to come in terms of some data on differentiation. It seems like that's the message.
Yes.
Okay. Awesome.
Yes.
It's like dealer's choice what we should start with.
We should start with limb-girdle because that's-
Yeah. Let's start with limb-girdle. Yeah, let's do that. This is probably one where maybe the unmet need is the highest. Anna, maybe you want to just lay the foundation in terms of the indication and basically the therapy that you guys will be bringing to the market.
Yeah, absolutely. BBP-418 is being developed for limb-girdle muscular dystrophy type 2I/R9. There are no currently approved therapies in this space. As you said, the unmet need is incredibly high. We're super excited about the potential that BBP-418 has in this indication. We read out our interim analysis from our phase III trial last year. In that study, we not only saw differences from placebo that were statistically significant and met all of our primary endpoints, but the differences observed were actually on treatment. There were improvements from baseline, which is pretty much unprecedented in the muscular dystrophy field. Then there were declines on placebo that were consistent with the natural history. Overall, this patient population is around 7,000 patients in the U.S. and E.U. We estimate currently in the U.S. is about 2,000-2,500 patients.
Got it. I guess, what's a launch in this indication look like?
It's basically a very concentrated pull point, so around 150- 160 MDA centers in the U.S. where the vast majority of these patients that are genetically diagnosed are currently treated. It's a very targeted, capital efficient launch. We're very focused right now on finding patients. We've mentioned that we've identified over 500 patients currently. As I said, most of those patients are currently at these concentrated pull points. Our field force is currently out educating physicians, payers, and we're anticipating that adoption will be very strong based on market research so far.
Yeah, I was going to say, in terms of the doctors and the education process, how long do you think that will take? Because this is an indication where there is really no therapies, is this going to be where basically every patient is a candidate essentially, or there are going to be some kind of narrowing of the actual true candidates that would actually be best to respond on the drug?
Yeah. Great question. What we are hearing right now is, you are absolutely right. Most patients are going to be considered a candidate for therapy here, and adoption is very high across all patients. The main sort of drivers of that are obviously that currently there are no available therapies. These patients are anticipating that they have decline year- on- year, and we actually saw in the interim analysis that were benefits as early as three months on the ambulatory measures, which is really driving urgency to treat. I think currently there is a lot of obviously patient need that will be driven by very strong patient advocacy groups too, that are doing a lot of the education on the patient side. Then in terms of physicians, as I mentioned, we already have the field force out there.
I think we are not anticipating a bolus though, just because I think the dynamics in these centers are that the patients currently go into centers about once every year or twice a year. So that might mean that sort of patients calling up physicians, there might be some delay in them getting into the centers.
I guess when you think about these patients and their kind of journey to diagnosis, how long does that take? What is kind of your method of even just finding these patients? Are there good ICD-9, ICD-10 codes to locate these patients, or is this still kind of like a lot more kind of digging and work that you need to do?
It's a combination. Basically right now there is a dedicated ICD-10 code, which is great. It went into effect last October, though, so it's still relatively new. We are seeing uptake already, and it is continuing to see new patients come in every month. We also have data from genetic testing databases where we've been able to identify patients as well. But we're anticipating that that genetic diagnosis will continue to increase. Based on market research now, it seems like the standard of care in these specialist centers is that people are getting genetically diagnosed as standard of care. It's really about patients getting to those centers, which is probably the delay in diagnosis. But once they're there, they are getting diagnosed efficiently with genetic testing.
Got you. Now, this is a different type of launch than, I would say, Attruby. More rarity is more focused. I guess, are there any key learnings that you can take from kind of the Attruby experience and kind of apply it to the BBP-418?
Yeah. I think that there are two different architects of launches, right? There is launch in a competitive market, which is Attruby and infigratinib, and then there's launch in a market which you're building, which is 418 and ADH1 and encaleret, right? I think that some of the similarities. There are some differences such as marketing and things like that. But there are some similarities, such as how do you design a process which quickly gets patients on drug, right? So not the kind of payer side of access, but more the patient and physician process side of access. Sure. I'll let Anna comment on that because one thing which obviously Attruby we have white glove service really working closely with the physicians' offices as well as the patients to get them on drug, and that is going to be key here also.
Maybe, Anna, I'll let you comment on how you guys are thinking about it and learnings from Attruby.
Yeah. We're out there right now talking to payers. The payer research has been incredibly positive as well. They're very receptive to the data that we've seen. As we mentioned, this is like they're not used to seeing placebo-controlled data in the neuromuscular space, and then also seeing these improvements from baseline and the functional measures is pretty differentiating. We're not anticipating big coverage hurdles for access and reimbursement. We are planning on offering a similar suite of services to what was mentioned for Attruby for getting patients on drug at launch.
I guess it's a good pricing analog for limb-girdle.
Yeah. The payers always refer to the exon skipping here as
Okay.
the most relevant pricing analog. I think, as I mentioned, the main difference here is that we're seeing functional benefits in a placebo-controlled setting, which they haven't really seen in that case. So, I think you could think about those as an analog as sort of the anchor, and then we might think about premium pricing on that.
Got you. Out of the three launches, we will discuss the other two, but do you think limb-girdle has the potential to be the fastest ramping, or do you think there is some, I do not know, friction points just because it is a new indication, it has never had a therapy approved there?
I will start, and then I will ask you to build on it. I think that we think all these three launches are going to be really good, strong launches. As Anna mentioned, we do not expect there to be a bolus or anything like that in any of these launches. Look, there are going to be new-to-market edits. These are markets which we are building. There is going to be diagnoses which we are educating people on. All of that, especially for limb-girdle and ADH1, is true, but nothing specific that I would call out as a pain point. It is all things that our team has diligently mapped.
Actually, these guys have done a great job of mapping each step of the patient journey, as well as each step of the physician journey, and making sure that at every point where there is potential for friction, we have a plan for how to overcome it. I think that they are all going to go really well. We feel good about them. Then I think your question was if this one will be faster than some of the other ones, and on that one, I am going to ask you guys to do some work.
You do not want to pick your favorite child?
I am told that that's not nice.
Yeah.
You can't do that one here.
Yes. Exactly.
That's fair. All right, well, maybe moving on. Let's maybe talk about encaleret and ADH1, so a smaller population. You guys have been doing a lot of work in identifying patients, so maybe just talk about the setup there for that launch.
Yeah. Very excited about it, because these patients who have ADH1, first of all, the prevalence is probably about 12,000. There are a ton of patients who are suffering with this disease. Currently, we've only genetically confirmed and identified about 500 patients. But we know that in the claims data, there is already about 2,200 patients. We know that there are more patients that we can go after and try and convert. So, huge unmet need. The drug basically normalizes the patient, because your blood and urine calcium levels become normal. PTH levels become normal. That is a profound effect. We're very excited about that. I think that the call point is concentrated, but not as concentrated as limb-girdle. I think here you're going after a slightly broader pool of endocrinologists. But what's very interesting is that there is extremely high overlap with hypoparathyroidism.
Actually, if you have non-surgical hypoparathyroidism, the guidelines recommend that you get tested for ADH1. What that means is we have a group of physicians who we can identify and target at launch and really try to, A, drive diagnosis there, B, drive awareness there, and then also try and convert some of their patients who are ADH1 patients onto our drug.
In terms of, I think, how we expect the launch to go, very similar to limb-girdle. I think that it should be a strong, steady launch building on top of each other. It is an autosomal dominant disease, so one thing which we have seen is once we find a few people in a family who have the disease, we can do sponsored family testing and find a lot more people who have the disease. That's actually a pretty interesting kind of difference between these two diseases.
I definitely do think that pricing here is going to be less than limb-girdle, but still extremely strong. I think the comps that we've given on the low end are YORVIPATH, which is about $300,000 and then on the high end, VYVGART, which is about $500,000. I do think it's possible we are closer to the high end than the low end, given the drug has significant benefits. That's how we think about it.
Of course, what's very exciting about encaleret is, and I know you're probably going to want to talk about this, is there is a huge expansion indication in hypoparathyroidism right behind it. We're very excited that we've kicked off a phase III trial there. We expect that trial to read out pretty shortly here by the end of 2027, definitely by early 2028. We have a beachhead with ADH1, and then we have a giant expansion opportunity with HP, and it will be the first oral agent approved in that condition, which I think patients will really wait for and want to be on.
Got you. Okay. I guess, maybe just talk to the strength of the data and what you believe mechanistically for the expanded opportunity and just general hypoparathyroidism versus ADH1, and what gets you confident in running that phase III?
Yeah. I think the first thing which gets us confident is our phase II data set. We did a small phase II study, 10 patients. These are some of the sickest HP patients. They didn't have the parathyroid gland. Completely independent of PTH, we saw normalization of blood and urine calcium in a majority of those patients. That's really profound benefit, especially normalization of urine calcium, which is a key unmet need area. I think second, I'm going to be a bit quick here because I know we are running out of time.
Yeah.
Neil actually expanded upon this on our earnings call. Mechanistically, there is a strong rationale for an agent acting on the calcium-sensing receptor in the kidney to have an effect in HP. I would really encourage you guys to listen to that, and I think he goes into a good amount of detail, which I can't cover here due to lack of time. That's just the papers which are coming out. Some of that is very new, they've come out this year, has also really encouraged us to go after it.
The third thing really is, we derive a lot of our confidence from experts in the field like Dr. Mike Collins at NIH, as well as other folks who really understand these endocrinology diseases. I think that that KOL excitement is the third thing which has made us excited about starting a phase III here and helping a lot of patients.
Got it. So yeah, maybe let's move to infigratinib just so we can get through it. But this one, excellent data, phase III data in achondroplasia, first oral agent in that indication as well. With the launch of YUVIWEL, we're definitely learning that the market is getting larger, and there's patients that were not really being. They didn't want to go on VOXZOGO. So I guess now a couple months now into the YUVIWEL launch, where are you guys thinking about, or are you more excited about the infigratinib upcoming launch and ultimately the opportunity there for an oral agent?
We are extremely excited about the infigratinib launch. We have been for a long time. What is remarkable is that we have a best-in-class drug, oral best-in-class estimate on efficacy. What is even more exciting, and we presented at ESPE, and we had a press release on this earlier today, is we are moving beyond height now. The benefits are not just on height. Yes, we talked about proportionality, which is a big deal in this community with our top line, and now at ESPE, we talked about sleep apnea, ear infections. The fact that infigratinib was able to show clinically significant large benefits on these measures beyond height, I think means that this will be able to grow the market significantly. If you look in Europe, about three quarters or so of kids are on some achondroplastic option. In America, maybe a fourth are.
Really that difference is moving beyond height and having an oral option. That, I think is the opportunity for infigratinib, and I think that is why we are very excited to be able to. We've partnered with the community, learned so much from them along our development journey, and now we are excited to serve them in the commercial realm, assuming that the FDA approves the drug.
Got you. Is this mostly new start market, or do you think it will switch patients? How do you think you will get your foothold? As you said, I think your data on body proportionality and that is going to be pretty meaningful for docs and for the patients. What do you envision early in the launch?
Yeah. We are going to be pooling from three segments of children. The first segment of families and children that we are going to be pooling from are children who are on VOXZOGO or YUVIWEL today. They are on it because there is no other option. They understand that moving beyond height is what they are looking for. They do not want to take injections, and so an oral option which has significant benefits beyond height would be appealing to them. That is going to be a key market for us.
Of course, that is a smaller portion of the children in the U.S. The second group of children are children who have tried VOXZOGO and for whatever reason, either because there was no benefit beyond height or because they could not take the injections, they have decided to go off of VOXZOGO. We know that those children and those families want something.
We suspect what they want is an oral option which moves beyond height, and we think that we will be able to offer it to them. That is the second group. The third group of families and children that we are hoping to help are folks who have never tried VOXZOGO, YUVIWEL. Some of them are needle phobic, some of them really want to be on an agent which helps on things like proportionality and not just height. That is going to be the third sort of segment that we are going to be targeting. I think we are going to see uptake in all three segments. I think that what we are most excited about is growing the market, so segments two and three. I do think segment one is also going to be important.
Got you. Maybe with the last two minutes here, Chief Business Officer, as you think about the kind of overall business, Attruby pipeline launches, we are going to have these launches. There is going to be a 2027 event. That is going to be exciting. What is next, right? That is what we are always worried.
Yeah.
It's like, what's next in the pipeline? Where are you guys going to be focusing your efforts and as you said, where are you going to take your resources and deploy the capital?
Yeah. That's a great question and I'm not surprised that Wall Street's asking what's next.
Yeah, exactly.
Here's how we think about it, right? I think our first priority is funding and accelerating the Attruby launch as well as the launches in limb-girdle, ACHON, and ADH1. Best and highest use of our capital. I think that's what shareholders will reward us probably for over the next 12 months. Beyond that, I think that we really want to invest in our pipeline, whether, a nd the main idea there is our hypoparathyroidism trial. And so that I also think is on investors' radars and something which we're prioritizing.
Beyond that, if we have excess capital, which we do right now, we are in the lucky position of having excess capital, having our losses come down over time, we always think about what's the right way to deploy capital. It could be through share buybacks, but it could also be at the right time, and our preferred path is to do it through organic growth. So we want to start new R&D programs, like I mentioned to you, and I think you are pretty close to this. You cover a lot of genetic disease companies. There is profound innovation happening in our space, and the opportunity to help patients is immense. So we have a sister company called GondolaBio, where we own about a 12%, 13% stake in it.
At the right time, maybe it's sooner, maybe it's later, but I hope it's sooner. We would like to integrate these companies, use the cash flows and the capital which we have to accelerate that, and to really make not just four medicines, but to make 40 medicines. And I think that that's the shape of company which investors, patients, and the community can be very excited about, and that's what we are aiming to build.
Chinmay, I think we'll leave it there. Anna, thank you so much.
Thank you.