Welcome to Day Two of our London Healthcare Conference. I'm Andrew Tsai, Senior Biotech Analyst at Jefferies, and it's my pleasure to have the BridgeBio team with me. To my direct right, Thomas Trimarchi, CFO, and to his right, Matt Outten, Chief Operating Officer.
Commercial Officer.
Commercial Officer, I'm sorry. Welcome, both of you.
Thank you.
Thanks, Andy.
Maybe for people in the audience less familiar with the story, would you mind spending a couple of minutes talking about the BridgeBio story, what you're trying to achieve, and what kind of milestones we can expect over the next 12 months or so?
Yeah, maybe. I'll start at a high level. Really exciting and unique moment for the company in terms of our ability to deliver for patients, many different types of patient communities at scale. I would say starting with our major commercial product, Attruby, what we're seeing is continued growth across all major segments of patients and prescribers, and importantly, continued momentum in terms of share growth in the frontline setting where we see the greatest opportunity for patient impact and long-term value for the brand. Flipping to the pipeline, which is here and now and delivering, we're just on the heels of two wonderful phase three readouts from our limb-girdle type 2I program and our ADH1 program. Those were, I think, kind of the cleanest top-line data sets that you can get in biotech.
We look forward to publishing those in journals and key medical conferences associated with those fields. We are working hard on getting those NDA submissions prepared and submitted early next year, and then we will turn towards ex-US filings for both of those brands as well. Looking ahead to Catalyst, the next one on the horizon is certainly our phase three readout for infigratinib in achondroplasia and other skeletal dysplasias, but we will read out a phase three in achondroplasia early 2026. The same story, we will be looking to distribute those data to the appropriate medical meetings and journals and prepare for NDA submissions.
We couldn't find ourselves this time next year with three approved products, one more on the way, which I think shapes up to be a pretty profound and unusual and unique profile for a company of this market cap range where you have a diversified top line, pretty explosive growth near term, and I think an engine that can sustain growth over decades to come.
Thanks. And props to you guys. I think I can only count positive events this year for you guys, hopefully more to come. Maybe to tackle Attruby that launched so far, walk us through why you think the peak sales potential of this drug, what you think it could be, why only 30% market share if you think this is a highly differentiated stabilizer, why not more? That'd be helpful.
Yeah, and I think we haven't said just 30. I think we've said 30-40. And then when we get there, we'll talk again and see what's coming after that. But I think we've been off to a very good start. The end of this month actually represents one year since launch. You guys have seen our first three-quarter results, so we've been very happy with the progress. I think we're really focusing on a lot of the same things that we started out doing, and that's been working. So I think we'll see where the end is, but I think we feel very comfortable with 30-40% in an ever-growing and expanding market.
There has never been a head-to-head study done within the ATTR-CM class, so it remains debated, at least on my side in the investor community. In the meantime, however, you're generating some real-world data that may help you make your case that Attruby is differentiated. What exactly are you guys gathering and accumulating in the real world to convince more doctors to prescribe more and payers to give more access, for instance?
Yeah, I think there's two parts to the story. I'll start on the first part, and then if Tom wants to add anything. I think our label for Attruby is very strong. We're the only drug that has near complete stabilization in the label. We were able to separate from placebo as early as three months. Again, not head-to-head, but no one's been able to show anything faster than that. Also, our reduction in hospitalizations at 50%, also the best that's been seen to date. I think between those items, doctors have been impressed, patients have been impressed, and I think that's a big reason why you're seeing physicians wanting to choose Attruby and patients asking for it when they go into the office.
We've also set up a number of what we consider best-in-class patient assistance programs, extremely generous, and we get drug to patient within just a few days, which I also think is a big differentiator compared to what others are doing in the market.
I would just say that we'll get more specific in terms of data and evidence that we're generating. Our medical team has got a very broad evidence generation plan that they're executing on. You will see us start to communicate a bit more through the course of 2026 on real-world evidence-type data sets, as well as investigator-sponsored studies. Of course, we're also running one company-sponsored study right now in primary prevention, and we'll be adding an imaging study on top of that starting next year as well. Very active on the evidence generation side, which I think will allow us to, in absent head-to-head study, continue to elaborate on our category-leading profile.
Very good. As we think about 2026, what would you say are the key drivers to volume, sales? So far, sales have grown linearly. It's not slowing down. What does it take for sales to accelerate even faster?
Yeah, it's a good question. I think there's kind of two things. It's like, one, the market continues to grow just by the number of patients that are being diagnosed, and I think we need to continue to encourage that. It's talking to doctors, educating patients, making sure that people are looking for this disease. Once you start looking for it, it's a rare disease, but it is somewhat common, and it still continues to be underdiagnosed. I think if you look historically at how the market's been growing every quarter, I don't think that slows down in 2026. In fact, I think the fact that there are now three companies out with an approved product in ATTR-CM, I think that actually helps to accelerate the finding of patients. Again, it's sort of like once you get someone to understand, it's not difficult to find a patient.
PYP scans are, you can get them everywhere. They're non-invasive. We're not biopsying the heart anymore. I think that drives quite a bit. In terms of what we have to do as an organization, again, I think our data speaks for itself. Very strong label. If you look at the conference presence and what's being said from the podium, even as recently as last weekend at AHA, there's a lot of really positive things being said about Attruby, and I don't see any of that changing in 2026.
Okay. I must ask then, is it your internal expectation 2026 we see an acceleration then?
Tom, I'll let you answer that.
I find the hard one to be.
Yeah.
I mean, so you've seen already in the trailing two quarters an uptick in the number of new patients that we're able to add to the brand period on period. I would expect that trend to continue. Again, I think the main driver of this is the fact that we are consistently gaining share in the first-line treatment IV setting and the fact that the overall pie continues to expand.
Speaking of first-line share, I believe my understanding is Bayer is launching in the EU and certain countries, and your first-line share already is close to 50%. Here in the U.S., I think it is just in the 20% ranges. Why the disconnect a little bit?
Yeah, so Bayer's off to an amazing start. I think we've been obviously really happy with their performance in Germany. I think there's a few reasons for that, but it's somewhat complicated in the sense from a reimbursement perspective, right? In the U.S., getting a prescription is one thing, and then you have to actually go through your insurance, where in Germany, you don't if you get the prescription, and once the drug is covered and reimbursed, it's paid for. I think there are some factors that you don't find in Germany that you do find in the U.S. healthcare. There's also three products being used in ATTR-CM right now in Germany. You're really only seeing two. It's just less of a pie being split. I think it's a great market when it's just based on the science.
We're at over 50% or whatever Bayer has released on that. I think our expectation is we'll continue to grow, and our hope is that Bayer continues to grow as well.
Yeah, I would just say they've been a fantastic partner. Obviously, you're executing extremely well in this launch. I think the fact that they're either currently or soon to be market leader in Germany demonstrates the potential of this brand when you remove some of the strange market forces that we have here in the U.S. We're really excited to see that. Of course, we also retain 30% escalating tier of royalty, so we own a significant part of those economics. Very good for all of us.
Great. In the meantime, as we think about Q4 trends, long story short, I feel like October the patient ads accelerated relative to your prior update in August in terms of the weekly patient ads, but I'm curious how are November trends shaking out?
You want me to take that?
Yeah, go for it.
Yeah, I mean, we have not obviously said very much. We keep our numbers kind of quiet until we release them at the end of the quarter. I guess what I would say, though, is that we are growing, right? We have shown that quarter over quarter, we do not anticipate anything stopping with a big focus on the newly diagnosed patients. I think we are continuing to focus on that and expecting growth to continue as well.
Yeah, I would just add, I mean, we've said this before, but weekly numbers are volatile. They bounce around, but we're seeing a consistent trend upward in kind of the periodic ads to the brand, which is exactly the right direction. I think as we think about fourth quarter, I do have to caveat all this by saying there's three fewer selling weeks usually in the fourth quarter due to the holidays. Just keep that in mind as you're trying to think about what your numbers should be at in 4Q.
Such as Thanksgiving.
Thanksgiving, Christmas, New Year's.
Understood.
Tends to slow down, yeah.
Okay. Come January, there's another major broker conference. Do you plan to share an update on then, or should we stay tuned for Q4 EPS later in February, March?
Yeah, the January event you speak of. I mean, we're thinking about what we want to have as our main message there, and there's a bunch of different ideas, but so stay tuned.
Okay, understood. You mentioned you're working on the, you're doing other studies in the meantime, like the ACT early pre-symptomatic trial. When does that data read out, and are there other clinical studies you're evaluating to bolster Attruby's differentiation?
Yeah, so there's no specific timeline guidance on the readout. That's mainly because it's an event-driven study and we're early on in enrollment, so it's a bit premature to put a firm timeline on that. As soon as we're in a position to, we certainly will. It's a very interesting study, I think, that is consistent with our scientific and research leadership in this field, where we're enrolling very inpatients that have a high risk based on family history and asking if we put them on Attruby before they have any symptoms of heart failure, can we actually prevent onset of disease? There will be an Attruby versus placebo, and that'll play out over the course of, I would say, the next couple of years.
We also are, I believe next year, we will be kicking off a cardiac imaging study to elaborate on the sub-study that we actually had in the Attruby phase III, where we showed actual reversal of amyloid burden in the heart, as well as improvement in cardiac function. We will be looking to elaborate on that through a larger prospective multicenter study and something we're very excited about.
Maybe one last question before we turn to the pipeline. We're approaching one year into the launch of Attruby. Does it make sense to provide guidance? What's your philosophy on that?
I mean, turn that around on you. Do you think we should give guidance? I mean, we're thinking about it. Look, I think the.
Just don't say I'm back.
I mean, look, we've evolved our relationship with the street in terms of the commentary on quarters. I think right now, it could be a good opportunity to start providing guidance, but at the same time, we've been given the wisdom from others that you should wait as long as you can. Curious what you think we should do.
I think it could make sense to think about it to help investors. I don't know. We can do a vote. I don't know. My take is it's appropriate. The timing is okay.
Yeah, okay. All right, we're looking at that.
All right. Moving to the pipeline. You have LGMD2I successful, ADH1 successful, achondroplasia hopefully successful too. Is it your intention to market these three drugs yourselves in both the U.S. and ex-U.S.?
Yeah, let Matt take that.
Yeah, so I think there's several things that are happening. We are building out our ex-U.S. capabilities. We do have an office in Switzerland right now, and the plan is to market these drugs ourselves. Of course, we have the great partnership with Bayer in Europe and Alexion in Japan, but we would also be marketing acoramidis in the rest of, not every country, but obviously then certain countries will take Attruby, what's known as Biontra, into those countries as well. There's quite a lot going on actually over the next 18 months for us with potentially three new drug launches plus the Biontra launches in those other countries. If you know people looking for a job, we're hiring.
Okay, very good. Maybe LGMD first filing early 2026. You will have a data update. I think you mentioned MDA conference in 2026. How much more, what can we expect you to share in that next analysis?
Yeah, so just taking a step back, this is a first-in-class therapy for a type of muscular dystrophy called LGMD2I/R9. We've read out our interim top-line data just a couple of weeks ago where we showed success on the primary endpoint with a very small P-value, P less than 0.0001. That was the agreed-upon primary endpoint for an accelerated approval path with the FDA. At the same time, in the interim, we showed really a profound improvement on two functional endpoints that we've disclosed so far, FVC or forced vital capacity, which suggests the patients can actually breathe better after taking our drug versus where they were at baseline. Also a significant improvement on 100-meter time test, again, suggesting better ability to ambulate versus pre-therapy. Really, I think unique and profound data in the context of many muscular dystrophy trials that we've looked at.
Yeah, we plan to present the data to MDA, publish in a journal following that. I think what you can expect at MDA is a deeper analysis on the primary endpoint and the key secondaries that we've shown the top line, but you'll have the context of baseline change over time, things like that that you'll typically see in a podium presentation. I think you should look for us to keep the drumbeat of presence at the muscle meetings and follow up with a journal article as well.
Thanks. Remind me, how many patients are there in the U.S. versus ex-U.S.?
There are about 7,000 in the U.S. and Europe. 2,000-3,000 will be in the U.S., the rest are in Europe. We see this as a clear billion-dollar-plus opportunity, no competition, none really in the pipeline anywhere close. With these data, I think we're tremendously excited about the potential to change patients' lives.
Let's just say you will be filing early 2026. This could be approved by early 2027. On day one, how many patients will you have line of sight to in the U.S.?
Yeah, so this is a fairly well-mobilized and diagnosed population. We know that because of the pace of enrollment. That's sometimes kind of like a biomarker for how big is the population in the wild. This enrolled about eight months ahead of schedule, 20% over-enrolled. We've also run a natural history that's got about 150 participants. There's another US natural history study. There are hundreds, if not over 1,000 patients that are kind of counted in clinical trial or actual observational studies and databases. There is a big pool of patients there. The biggest thing that we're going to be trying to drive out into the community in the next year is really just awareness and testing. Most limb -girdle patients have a diagnosis of limb -girdle. It's just knowing that you have 2I versus another type, that's something we need to work on.
There is also some belief that there may be some misdiagnosis within the Becker population, but that's also going to be a priority for us.
Great. How does this interim finding, I mean, you're not just seeing stabilization procedures, you're seeing improvement in FVC. How does this instill confidence in the final primary endpoint? I think out to 36 months for this phase three study, which is North Star, I believe?
Yeah, it's North Star. I mean, we were not expecting to be able to observe a statistically significant change in any of the functional endpoints at 12 months. That's the whole reason for the regulatory strategy leading up to the top-line readout, which was to demonstrate that alpha DG, our biopsy-based marker, is reasonably likely to predict subsequent actual clinical benefit. Now, we've seen actual clinical benefit at 12 months in a subset of the patients, which really is just an upside surprise in terms of the effect size, which we were not anticipating. I think it's very de-risking for the longer-term endpoint. Our team is working tirelessly on getting in front of the agency to talk about kind of next steps.
Okay. The same compound is going after another LGMD subtype maybe next year. Should we expect a similar trial design as 2I? Or is it 2I that you're pursuing?
2I, there's 2M and 2U are smaller indications with the same kind of same pathomechanism. Then there's also a condition called Fukuyama that has the same kind of defect in the alpha dystroglycan complex where this medicine could be used as well. That's about 1,000-2,000 patients in Japan, which we'll also be looking to run an expansion trial there.
Okay, thank you. Shifting gears to ADH1, also successful filing an NDA early 2026. So how many patients? What's the peak sales potential? How are you thinking about price?
Yeah, so this is encaleret, which is our calcium-sensing receptor inhibitor for hypoparathyroidism. The first indication is a genetic form of hypoparathyroidism called ADH1, which arises from an activating mutation in the calcium-sensing receptor. So mutation turns it on, our molecule turns it down. Now, what we've seen to date in the phase three, we're actually remarkable results where these patients who are normally hypocalcemic have to take a ton of calcium supplements to manage their blood calcium to anywhere near the normal range. As a consequence, it ends up getting dumped out in the urine, and you're basically destroying the kidney over time. No effective therapy today. What we showed in our phase three was that 76% of patients could completely come off of their standard of care supplements, go on encaleret, and normalize both blood and urine calcium at the same time.
We've also seen 91% of patients have normalization of serum PTH levels. Basically, you take encaleret, you stop taking supplements, and your disease is functionally fixed by looking at these lab values. Really exciting data. It'll be really important for the field. In terms of EPI and market opportunity here, we see in the genetic databases, actually, we published a paper on this recently, there's around 12,000 carriers of the ADH1 mutation in the US, similar number likely in Europe. We don't know how many of those we can get a correct diagnosis or how many of those are actually going to be symptomatic. What we know today is there's somewhere between 3,000-4,000 that are diagnosed or at least suspected to have ADH1 that are symptomatic and will be eligible for therapy.
Similar to limb -girdle 2I, over the next year, we're going to be deploying our field medical force to drive awareness, to get physicians using the genetic test so that we can have confirmed diagnosis of ADH1.
Understood. What's the most logical venue next to share the detailed data?
Could be Endo or perhaps a publication early next year.
Thanks. Separately, you're expanding into PTH by starting a phase three next year in 2026. Any color around the timelines to the data readout? Could it be faster than the time you took to enroll and complete ADH1, for instance?
Yeah, certainly the enrollment times could be slightly quicker there, although I would just call out that it only took us about 18 months to enroll the ADH1 study. That's a smaller patient population, and it's one where, especially when we started that study, awareness of the disease versus just idiopathic hypoparathyroidism as a kind of lumping indication was lower than it is today. Yeah, there's something like four or five times as many patients with chronic hypoparathyroidism broadly versus ADH1. We do expect that could enroll quicker. Need to get some regulatory feedback from the agency on the phase three design, and then as soon as we can, we'll be kicking off the phase three. We see ADH1 as a clear billion-dollar-plus opportunity where no competition or any coming behind us, and there's never been any effective therapy to date.
First, best in class, we should own that market. I think chronic hypoparathyroidism is somewhere between a $3 billion-$5 billion or maybe even larger global opportunity. It will be more complicated because there is competition, but I think there is room for multiple segments and multiple winners.
Okay. And then last couple of minutes, achondroplasia, again, data early 2026. Talk about why you think this compound could be differentiated versus competitors.
Yeah, so I would say it's differentiated in two ways. One, it's the only agent out there that treats the disease directly at the source. It targets FGFR3 directly. The approved therapies that are ahead of us are targeting CNP, which is kind of downstream. We're hitting the genetic driver directly, and our goal is just to normalize the aberrant signaling that causes the condition. We've seen in phase two that when you normalize FGFR3 signaling in these children, you can have a profound impact on height, so an increase in their height velocity that is highly meaningful to these children and their families, as well as some early, but I think exciting data on proportionality, which would be a game changer if we could replicate that in a larger study.
In terms of what we're looking for in the phase three, I think, sorry, I forgot to mention, the other differentiating factor that is super critical here in this category is it's an oral small molecule that's given once a day. This is a condition where you're going to be treating children from infancy through closure of their growth plates when they're somewhere between 15 and 18 years old. Therapies ahead of us are injectables, either daily injection or weekly injection. We know that that is a significant burden for these families because we spend a lot of time with them, and they tell us, and it's a significant barrier to initiating therapy, and it is also a reason for discontinuation. I think that is going to be game-changing if we can come to market with an oral therapy.
What we're looking for in the phase three is essentially, on the efficacy side, we would like to see primary endpoint data. The primary endpoint is change from baseline AHV versus placebo. We'd like to see that in line with what's been shown from the CNPs to date. If we can provide that with a manageable safety profile, meaning safety consistent with phase two to date, which is little but some low-grade hyperphosphatemia or phosphorus elevation and no other problematic FGFR-related issues like ocular tox, if we can show that with an oral ROA, we think that has the potential to really lead this market.
Okay. And then proportionality, cherry on top, kind of.
I wouldn't expect that in the top-line readout or the 12-month endpoint. I think it's a bit early. It might take longer for that to evolve.
Thank you so much for the update. Thank you, everyone, for listening. That's all the time we have. Thanks.
Thanks, Andy .