All right. If we could get started, I'd like to welcome everyone to the Piper Sandler Healthcare Conference. With us is our next company. We have BridgeBio and Justin To, who is head of their Infigratinib, Skeletal Dysplasia program, and Chinmay Shukla, VP of Strategic Finance. Welcome, gentlemen. I guess, you know, first of all, congrats. I think, you know, if I look at your stock price, you know, you guys have done tremendous, since the start of the year, up about, I think, 160% versus XBI of 30%. A lot of success there. Maybe we could start with, you know, Attruby clearly being, you know, one of the big drivers of that success this year. Can you talk to us about, you know, how the launch has gone so far and where it is compared to your expectations?
Yeah. Happy to talk about that. First of all, Brian, I want to thank you and the entire Piper Sandler team for inviting us to be a part of this wonderful conference. I also want to thank all the investors for taking the time out to spend some time with us today and to hear our story and to support us on this journey. To start off on Attruby, I'd say the launch is going extremely well. If you rewind a year back, we had said that our goal was to establish Attruby as the preferred stabilizer of choice for treatment-naive patients. That basically is calculated by us through our share in the first-line setting. I think I would say that we've done really well on that front.
We announced on our Q3 earnings call that our share is now well into the 20% range, and our long-term goal, you know, continues to be 30-40%. Internally, we are striving to see if we can be market leaders in this category just given the power of this molecule. It comes down to three things for us. The first thing is, clinical data which is on our label. We're the only product which has near complete on its label, so we're a near complete stabilizer. We also have the best point estimates, all of which are on our label, whether that's 50% reduction in hospitalization at 30 months or the 42% reduction in ACM and hospitalization at 30 months, or whether it's very importantly, three months time to separation, which really does matter in this category.
I think the second sort of stool of the table is, continued clinical, evidence generation. You have seen us, you know, present at all the big cardiology conferences this year and really solidify Attruby as a differentiated molecule, right? It is not just another stabilizer. It is, it is a better stabilizer. It is the next generation of stabilizer. That has been pretty critical for us, I would say. The third thing which I would say we have done really well is we have made it easy. That is what our market access team has always tried to do. You know, whether that is their 28-day free trial program, whether it is all the white glove service that the company provides, through the patient access liaisons, through the field reimbursement managers, all of that together has helped make it easy to start and stay on Attruby.
Together with the data on the label and the evidence which continues to be generated, it helps us keep getting share in the first-line setting, which obviously is the critical setting. And, you know, we continue to do well in the switch side also.
You know, you've had some really strong progress over the last several quarters, since launching about a year ago. Can you talk to us about, you know, Q4, what we should expect? There is holiday season. Should we expect some impact on that? There's also some tailwinds as well with, you know, Pfizer having announced that they plan to discontinue Vyndaqel and remove that from the market by end of December. Could we expect that as a tailwind potentially in Q4, or do you expect that that's more of a tailwind for 2026 from that removal?
Yeah. Those are really good questions. I would just say that, you know, the most important thing for us is share in first-line setting. That keeps going up, every quarter. I think so far this quarter, we've not seen anything which would make me say otherwise. We had a very strong October, very strong November. Our share in the treatment-mining setting keeps going up. We're very excited about that. Our switch share has also stabilized. Having said that, I think it is important for folks to know that there are three fewer selling weeks, effectively three fewer selling weeks in Q4 compared to all the other quarters. You know, we just have fewer days when our sales reps can go and talk to the physicians, and there are fewer days when physicians are prescribing.
That does have a bit of an impact on us, obviously. As it pertains to the Vyndaqel discontinuation, I would say that that's more of a 2026 story. I think the forces out there and, of course, you know, given the fact that physicians have to do new paperwork to switch the patients over from Vyndaqel to Vyndamax, it's a natural opportunity for our field team to go out and say that, "Hey, if you're doing the paperwork, why not just switch them to a better stabilizer?" Certainly for phys there are many physicians who believe that Attruby is a better stabilizer. So that message does work.
I do think that, as we've discussed before, Brian, I don't think that we're going to get a lot of those patients just given the fact that our competitor is entrenched in that space. Where we will get some help is more through 2026. There were settings where Vyndaqel was being used over Vyndamax, and I think that we'll have more success in converting some of those accounts to writing Attruby in the first place. I think it's going to be helpful for us throughout 2026. I wouldn't really expect any kind of burst of demand in Q4 from it. Having said that, you know, we try to get every script we can.
Great. You talked about some of the accounts that you could potentially convert. Is it more like the VAs of the world where, you know, Vyndaqel has had some market share in those types of accounts?
Yeah, that is correct. I think that in certain accounts, we've seen that they really focus on overall cost to the system, which kind of makes sense to us. Obviously, given Attruby's price point and the profound effect on hospitalization and time to impact, those are natural accounts where Attruby should be used first in our view. That's kind of what we would expect to see. I think that we're having good success on that front.
The company has success in the free 28-day, you know, program that was introduced early on. Clearly, you know, you're doing something right because Pfizer has kind of copied that program for Vyndamax. Do you expect that you would face now increased pressure because of the Pfizer program?
That's a good question. Yes, I think, what's the word saying? That imitation is the best source of flattery, something like that. I think it's great. You know, I would love for our competitors to copy all our programs which are very patient-friendly. I think ultimately we all in the industry, and certainly at BridgeBio, exist to serve patients. We're a service organization. We're happy that patients have that option. Having said that, that change was made back in May. I think investors are maybe catching onto it now, but that's been in the marketplace for about six months, and we've seen no impact from it. Ultimately, you know, all these are very important and good things to think about, but ultimately what's important is clinical differentiation.
I think that increasingly we are convincing more and more physicians that Attruby is clinically differentiated. It's a superior product. This is a life-threatening disease. Without any therapy, you know, half the patients roughly die in three years or so. It's what you saw in, in the Tafamidis trial. I think that it is very important that you're on the best therapy. I think that Attruby's clinical superiority really is the reason why we're gaining so much share so quickly.
That's good. And then I did want to talk about, also the diagnosis rate. You know, clearly, you know, the diagnosis of ATTR-CM has increased since Pfizer launched Vyndamax in 2019 and has continued to steadily increase. Where do you feel, where do you think we are, from a diagnosis standpoint? Have we kind of, you know, are we closer to the ceiling, or is there significant more room for growth?
No, I think there is significant more room for growth that this is still a extremely underdiagnosed disease. You know, we track every stage of this funnel. You know, I'll start at the PYP scans. If you look at the number of PYP scans, they've grown at a CAGR of about 30% over the last few years. That's starting at a already high number, back in 2019. You know, we are starting to see more people, obviously, at the top of the funnel. The next leg of the funnel is how many of those diagnosed patients get converted to treated. Because of the IRA, we have seen actually that number also go up quite a lot because the drugs are now much more affordable for patients.
You know, I think we said on one of our earnings calls that 90% of Attruby patients pay $0 copay. That really helps. For the rest of the patients also, it's $167 a month at the most. That gap has continued to shrink. You can see that, you know, ultimately this results in more patients being on therapy. If you look at all the three products which are out there, last year we used to say that there are 2,000-3,000 newly diagnosed patients coming on therapy in the treatment-mining setting every quarter in the U.S. This year, I think it's at least 3,000. It could be a lot higher than that. Finally, you can look at it in the sales, right?
Like, I think that if you just look at the overall ATTR-CM category sales, Q3 2024 to Q3 2025, despite the fact that, this year, because of the Inflation Reduction Act, Tafamidis has to pay a 20% rebate. So effectively, you need 25% more volume. You can see that Pfizer's sales have not really gone down. You've added all of Attruby, which, you know, like you classified as had a very strong launch. And then you also added all of Amvuttra. I think that we are very much in the early innings of this. I think that this is going to take many years before we actually find all the patients. But, it's a huge market. It's growing very quickly, and it's not showing any signs of slowing down.
Clearly, heading into 2026, you do have some tailwinds with Vyndaqel with increased diagnosis. You know, one of the other questions that kind of comes up is, you know, the Pfizer litigation. You know, they have, I think, four generics that have filed against Vyndamax/Vyndaqel in different formats. You know, this is clearly something, a question that gets asked frequently by investors. What's, you know, how does BridgeBio view this in the event that a tafamidis generic comes into the market in 2028?
Yeah. It's a great question. What I would say is that the first thing to focus on is the fact that Attruby is differentiated. It's not just another stabilizer. It's a superior stabilizer. As we've been discussing throughout this discussion, you've seen that in terms of physicians are reaching for it above all other products. It is our job with continued evidence generation to keep reinforcing that, to keep showing that it's a better stabilizer. It's a superior product. You can look at all the sort of literature on this. You know, when first to market, less potent molecule goes generic, the second to market, more potent molecules, their sales do not really go down. Maybe the growth rate changes a little bit, but it still keeps growing. You saw that in the statin space. You saw that in the pH space.
You saw it in the factor 10A space. I mean, I can keep going on and on. Actually, I haven't found a single example where the reverse is true. That is obviously the most important thing, and that is what BridgeBio focuses on. I think for investors, I also just flagged that given the Vyndaqel discontinuation, it really doesn't matter if Vyndaqel goes generic or not because Vyndaqel and Vyndamax, importantly, are not substitutable at the pharmacy. You would have to write a generic Vyndaqel script, which is just a much higher bar. The Vyndaqel stuff we have stopped paying a lot of attention to because it is irrelevant given the discontinuation. We'll see what happens on Vyndamax. I think everyone knows our view on that. I'm not gonna repeat it, but I think that the most important thing is clinical differentiation.
Great. I do wanna get Justin involved. You know, also another big data coming up in 2026 with infigratinib and achondroplasia. Can you just maybe let's start at a high level?. You know, right now we have BioMarin with Voxzogo on the market, Ascendis with TransCon CNP currently in, you know, regulatory review at FDA. How do you think about the market, you know, two, three years from now as you're about to potentially launch into the market with, you know, CNP drugs that are already, you know, in the marketplace?
Yeah. Happy to answer that. I think the achondroplasia market's pretty well established, you know, in the United States, internationally as well. I think there has been a really significant appetite, a growing appetite for more treatment options on the market, not only from clinicians but, more importantly, from families as well. I think there's specifically an appetite for more convenient options, right, specifically in oral therapy. I think that's where infigratinib is really well positioned, potentially as the first oral option for achondroplasia, something that, not only is just an oral but can be the first therapeutic option to target the condition at its source, at the FGFR3 gain-of-function mutation.
I think that's part of the reason why we're so excited between that and from what we've seen in the phase two data set, which was best-in-class efficacy and change from baseline HB and, and potentially impacting proportionality and height and D scores. I think that's what makes us excited for the upcoming phase three.
On the phase, you know, we, you talk about the oral convenience.
Mm-hmm.
When we start to look at the data from the phase three next year, should we be comparing, you know, annual height, height velocity, to the CMPs in terms of, you know, changes versus placebo adjusted to baseline?
Yeah. I've got a few different ways to answer your question there. One is I'd probably take two kind of key commercially successful. From our market research, a FGFR3 inhibitor that's oral with the same efficacy, everything else the same as either once daily or once weekly injectable, would take a majority of the market, anywhere from 50-60% of the marketplace. That's what's gonna take to win in this marketplace. Now, in terms of what we would like to see, we would like to see that, right, something that is just at least as good from a change from baseline HB as the CMPs. Again, it's gonna be a little bit not quite an apples-to-apples comparison 'cause compared to the other phase threes that were run this phase, we're gonna be enrolling a broader age cohort, ages 3 - 18.
BioMarin did 5 to 18, Ascendis did 2 to 11. You know, the kind of the ends of each of those age ranges, the younger, youngest age range and the oldest age range, we know that there tends to be less treatment effect in those. Conservatively, you know, I think we would wanna see anywhere from, you know, about 1.5 centimeters per year in change from baseline. I think the best way to compare apples-to-apples across all three trials would be to look at the secondary endpoint of height Z score, which effectively normalizes for kind of the improvements relative to the age and sex of the population. From what BioMarin and Ascendis saw, they saw a 0.3 improvement in height Z score. That's kind of gonna be the bar for us to look at as well.
Now, the other kind of key secondary measure to pay attention to would be improvements in proportionality. Again, in the BioMarin and Ascendis phase three, they were not able to see an impact. In the phase two, we were able to see an impact at 18 months. I think it remains to be seen whether or not we see an impact at 12 months. If we do, I would consider that like a home run. You know, if not, I do not see that as an issue.
From a safety standpoint, what would you wanna see?
Yeah. I know there's been a lot of talk around, you know, the issue of hyperphosphatemia, you know, given that is a, a potential issue with FGFR inhibitors. Really, when we talk to clinicians and even families, they're not really so worried about these kind of transient phosphate elevations because they tend to not be associated with clinical risk or any type of treatment management. Actually, you know, other growth promoting agents that pediatric endocrinologists are familiar with, such as the once daily or once weekly growth hormone, they have hyperphosphatemia rates north of 20% without any type of required monitoring of the labels. I would say kind of our bar for what we would wanna see is somewhere around, you know, no more than 20% of low-grade hyperphosphatemia.
Perfect. Perfect. Okay. I guess, you know, with that data, do you feel like that data could potentially unlock the U.S. market? Because it seems like when you look at Voxzogo, they've had better success outside the U.S. compared to the,
Yeah. No, again, a really great question, a really timely question. I think there's this and there's a narrative that, you know, most of the achondroplasia market is international. Don't get me wrong, there is definitely a large international opportunity for achondroplasia that we will look to kind of take advantage of as well. I think the U.S. opportunity's underappreciated because there's a high degree of needle phobia and a high number of families who are kind of on the fence about treatment. They're not families who would never wanna treat, but they're on the fence. Part of the reason why they're on the fence is that, you know, the burden of having daily or weekly injections is quite high for a condition that's not lethal, right?
You know, from discussions with many families and caregivers, they would really be open to trying and starting treatment if there was an oral daily option. We really think having an oral option would really unlock a sizable portion of the opportunity. We would estimate that to be more than half of families with achondroplasia actually would be those who are on the fence right now.
How do you think about the pricing relative to the CMPs?
Yeah. I think it's a little bit too early. We'll have to see what the data looks like. Yeah, I would use the kind of potentially look at the CMP pricing and kind of how we would anchor it.
Outside the U.S., clearly, you know, BridgeBio made a decision with Attruby to partner with Bayer, who's now selling and it's launched in Europe. What's the plan for infigratinib if the trial's positive? Would you potentially engage a partnership similar to the Bayer partnership?
I think the bar for that would be pretty high. You know, I never like to say never. We're always open to finding the right solution, and we do believe in the best owner hypothesis. You look at ADH1, you look at BBP-418, you look at infigratinib. We're trying to keep global rights to all three programs. Certainly, the situation of the company is a lot different than it was two years ago. The scale of investment required to commercialize these three assets, very importantly, is a lot smaller than the scale of investment that would have been required for Attruby. Different situation, different assets, different company situation. I think that, you know, we're very well capitalized, which also helps in all these decisions. Never say never, but, you know, the bar's high.
Got it. Got it. I guess, you know, with infigratinib, you're also developing in the second indication of hypochondroplasia. What are the read-throughs from PROPEL3 into that second indication, if any?
Yeah. I think there's a pretty significant read-through given the fact that hypochondroplasia is also caused by gain-of-function mutation in FGFR3. For achondroplasia, it's a G380R gain-of-function. For hypochondroplasia, it's N540K mutation there. Again, you know, we'll have to see what the data reads out from our Excel program hypochondroplasia, which the phase results will be available by the end of next year. We do think mechanistically and from preclinical data, there should be a pretty good read-through.
Got it. Got it. You know, you had this fall two data sets that were disclosed, so positive data sets across both Encaleret as well as, you know, the LGMD program. What are next steps? When can we expect the regulatory filings on each?
Yeah. Maybe I'll just take a minute to talk a little bit about the two data sets because they were really tremendous data sets, and we are very, very proud of both the data sets. I'll point out a couple of things. Normally, when you go from phase two to phase three, you tend to see a dampening of the effect, and that's pretty common across all trials. What's remarkable here is, you know, you look at the ADH1 trial, the point estimate is actually higher in the phase three than it was in the phase two. I don't recall the last time I've seen something like that. You know, we went to a much broader number of sites, much broader number of mutations, and still you saw this very robust effect.
The second thing, which I'll just point out about the two data sets, which is really unique, is, you know, the goal for all of us developing therapeutics is to obviously "cure a disease." I think we never really get to curing most diseases. In most cases, you slow the decline of the disease. Once in a while, you get a great drug like Attruby which really stabilizes and halts the disease progression. What's unique about Encaleret and BBP-418 is that you are starting to see a cure, right? For Encaleret, you saw more than three-quarters of the patients have complete normalization of their blood and urine calcium, which is, you know, functionally a cure for ADH1 patients. For BBP-418, what you saw is an improvement on clinical endpoints compared to a deterioration on the placebo arms.
I think that these data sets are quite unique scientifically, and we are very proud, you know, all of us who work at BridgeBio, most of us are PhD scientists. We are very proud of the data that's being generated. I think in terms of next steps, you know, if we're talking with the agency, we're in very active dialogue, and we expect to file NDAs for both these programs in the first half of next year. We expect to launch them Q4 2026, Q1 2027. That's kind of the time frame. Yeah, that's what I would say there.
For LGMD, will we get more follow-up on the functional outcomes? I know you gave us, you know, some interim data sets which look really good. In terms of longer-term follow-up, could we expect that in 2026?
Yeah. I think the important thing there is we first have to align with the agency, right? It's an ongoing trial. The most important thing for us, just given the profound effect that we have seen, is to maintain the integrity of the trial. We shared everything that was pre-specified in the SAP. Beyond that, what we can share, we first want to talk to the agency. We really respect their views over here. Once we have alignment with them, we will talk about it, and we will be very excited to share more data from that trial. I know that that's not a direct answer, but really, it depends on what the regulators tell us we are and are not allowed to talk about.
Perfect. You know, we've got a minute left. I do wanna ask, you know, we talked about price points for each. Maybe can you, now that we have the data in hand, can you talk a little bit about how the company's considering, you know, price points for each program?
Yeah. We haven't completed our final pricing work. I wouldn't want to comment too narrowly on pricing. Having said that, we expect these to be priced in accordance with the opportunity size. Encaleret will be priced for the ADH1 opportunity. I know that there is an expansion opportunity which we're excited about, but at the start, it'll be priced at the ADH1 opportunity. BBP-418, similar results, you know, priced at LGMD2i opportunity size. If you look at rare disease analogs, on the lower end, you have something like Voxzogo or Crysvita, which is around $400,000. On the high end, you have something like Exondys 51 or Vyndaqel, which is closer to $750,000-$900,000. That's a pretty broad range, but we'll be somewhere there.
We are a responsible company in terms of pricing, but at the same time, we recognize these are smaller indications, so we have to price them for that opportunity size. I know you didn't ask me this question, but I just wanted to, I would be remiss if I didn't tell investors that they should look up the ACC guidelines which came out for ATTR-CM. A couple of interesting things that I'll say because I know we're out of time. One is that there's no evidence of combo therapy having a benefit, which I think will help, you know, on some of that front. I just think it's an important thing to note scientifically. The other thing which I think is pretty directly helpful for Attruby is that they talk about a drug-drug interaction between Tafamidis and high-dose statins causing rhabdomyolysis.
That is obviously, you know, lots of these patients are older and are on high-dose statins. That is an opportunity for our field force to educate on. Sorry, I stole a question from you there.
No, no worries. No worries. This is super helpful, and thanks for, thanks, Chinmay and Justin, for attending the Piper conference. Looking forward to more updates and progress over the next several months.
Thank you, Brian.
Thanks for having me.
PIPER team.