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

Please to introduce from BridgeBio, Neil Kumar, Chief Executive Officer. We only got 30 minutes to cover 3 hours' worth of content. So maybe start with a very quick snapshot of the company and what we have to look forward to in the months and the quarters ahead from BridgeBio.

Sure. Well, first of all, thank you so much for the invitation here, and it's been great partnering with Cantor through the month. At a high level, BridgeBio is a company that seeks to discover, develop and ultimately, commercialize new therapies from Mendelian diseases. This year, our focus has been primarily the commercial preparation around acoramidis, which is our drug for ATTR cardiomyopathy and the continued execution of our late-stage Phase III pipeline which includes achondroplasia, ADH1 and LGMD2I.

All right. That was a very quick snapshot. Let's dig in first on acoramidis. We've had now a couple of weeks to digest the vutrisiran data. What's the feedback that you're hearing as you're preparing for commercial launch in the TTR cardiomyopathy?

I think, yes, it was an exciting moment for the patient community, lots of different therapies that are going to be available. I mean when we started in the field, ATTR-ACT was just about to read out. And effectively, ATTR cardiomyopathy was driving 42% mortality rates over 30 months. And now we've seen with some of our data that at least in the real-world setting and in our Japan Phase III, you can get 100% survival rates over the 30 months. So that's a remarkable advance across the industry. And I'd say, as I've said to others, the multiplicity of sponsors suggest to me that the biggest problem in this space which is a lack of diagnosis of patients that's going to be tackled. So coming out of ASC, I think we were proud of the data that we were able to continue to publish. One was really tying that not together between serum TTR, ever increasing levels of serum TTR and ever better levels of survival. And then the second was an analysis of patients in our clinical trial, where they come from tafamidis and onto acoramidis, looking at serum TTR levels and seeing what happens, and you saw almost 50% increase in serum TTR, 3 mg per deciliter increase in terms of serum TTR. And recall, we had already presented data suggesting that for every 1 mg per deciliter increase, at 28 days, you actually see a reduction in mortality of about 5%.

Where are specialists to your sense and really appreciating the emphasis on monomers as disease driver as opposed to just TTR in general?

I think it's a mixed bag, obviously. Our understanding of the path and mechanism of this disease is pretty tightly correlated with every time you do better in limiting the amount of amyloidotic precursor or toxic monomer, you do better for patients. I think we've seen that now across 3 data sets. Although there are cross-trial comparisons, I think the 42% relative risk reduction that our drug has and the 3-month operation is the best. And I think that, that is consistent with the fact that we are limiting the amount of toxic monomer more than a partial knockdown or a partial stabilizer. Where specialists are on that? I think some people are deep experts on the biophysics and biochemistry of tetramer and ultimately, monomer deposition and others are coming up to speed on it. So it's a bit of a mixed bag, and it's up to us to educate.

Maybe you can tell us where you think you are in that education process. Do you think they're going to be early adopters? What might they look like? Who are the late adopters, and what do you need to do to convince them?

I'd say we're in the very early innings of our education process. I just remind everyone that we're in a very sensitive pre-promotion stage right now. We don't have our label. We're not approved, and we're going to abide by those rules. So education, really, first and foremost, has to start once we get the label and once we're out there. I just came from our national sales meeting. We have a very, very competent and experienced team that's ready to go at the right moment. And so I think we've got to get out there and start that. In terms of early adopters, I think it starts with the clinical trial sites, and the folks that have experience with that acoramidis. It's obviously across the Phase II in the Phase III, and we'll build from there. Yes.

One thing that we've heard from docs is a belief that a lot of patients are doing just fine on tafamidis. I'm not sure how they even draw that conclusion. But in theory, if you've got a better product, every patient could benefit. What part of the tafamidis market do you think is up for grabs? Or how much of it could you put into play with education?

It's a good question. The market research that we've done as sort of recently as 2 months ago, so post HELIOS-B, but prior to ESC suggests a pretty broad range, somewhere between 15% and 40% of patients depending on the practitioner to be understood as effectively progressors with the family. So how people define that? First and foremost, NT-proBNP is probably the most common way that they define it, but it could be quality of life deterioration. It could be observations that they have and around how the patient is feeling. It could be serum TTR, but that's a minority of physicians. We'd like to see it be a more used indicator of response. But I think it's in that 15% to 40% range where physicians would say, yes, they are responding. The drug is obviously active, but there's more we could do for this patient. And I think in the real-world evidence studies that were presented out of the [ Moore ] Lab and out of Dr. Masri's lab, you see that the rates of survival on tafamidis somewhere in that mid-70s percent range versus what those same sites are experiencing with acoramidis, which is from the 90% to 100% range of survival, suggest that we can actually get patients to a higher level of survival, and certainly from the hospitalization standpoint, lower levels of frequency of hospitalization.

Where do you think you'll have the fastest in roads since the market isn't going to come from taking patients, perhaps not doing well enough on tafamidis and converting them to acoramidis, or is it going to be more in the identifying new patients where there's not a switch consideration?

I think it's going to be new patients to start. That's certainly our focus. It's not the naïve population. There's really kind of 3 populations out there. There's the undiagnosed right now. That's the vast majority of patients. And we're excited to play a role, as I mentioned earlier, in finding those patients. Then there are the diagnosed but not on drug. And my hope is the things we do and also the IRA can help those patients access important medicines. That's actually quite a few patients. There's 47,000 patients or so, 50,000 patients diagnosed. Today only, about 20,000 on drug. So that's a large chunk there. So those 2 chunks are our primary focus. And then the switchers would be the next piece if physicians feel like their patients aren't adequately managed on tafamidis.

So maybe we can talk about the efforts find those new patients. Where do you go that maybe Pfizer hasn't been? I think you have a new cards lab partnership to help with diagnosis. Maybe you can give us a sense of what we might expect on that for that effort.

Yes. So on that partnership, we're applying a new technology called AI, artificial intelligence, have you heard of this? It's...

Vaguely. Sure, yes.

So basically, you could from [ ECOS ] and other lab data effectively start to identify individuals that may not be otherwise identified through technetium scans or you may not have thought of using the technetium scans, so you can pre-identify them and move them into the diagnostic criteria. It's also going after the high-volume heart failure practices that haven't been quite as educated on ATTR cardiomyopathy. If you look at the call point, I think a year ago, we were talking about a call point of maybe 80 centers of excellence that accounted for almost 80% of the scripts and now something like 180. So it's actually -- for 80% of the script. So it's actually enlarging, and I think we can play a material role in trying to find patients. The other thing I should say is there's a massively underserved community in the African-American community that has obviously the V122I variant at higher frequency than the overall population. We all collectively have to do a better job of getting out and educating and getting medicines to that community. I think that is an opportunity for us to have our medicine more broadly used as well.

And with an intensifying commercial competitive dynamic, what -- first foray really for Bridge into commercialization efforts, what should give investors the confidence that you can get this right?

Yes. I mean, first and foremost, I understand if people have questions about it. To your point, it is our first commercial foray, and we've never done it before. So it's right for people to ask the questions. I start with the data. I think the data are wonderful and present a great opportunity for physicians to get their patients on a great therapy and an alternative to what's out there right now on tafamidis. I think secondly, this is still a rare disease. It's a field force. We're not going to comment on specific numbers, but we're not [ thinking ] about the field force of several hundred people. It's a rare disease. You're talking about MSL forces of well under 50. And I think you're talking about the type of white glove service that a rare disease company can be good at. Now obviously, our experience with NULIBRY which is maybe the rarest drug ever commercialized. I'm not saying that, that is a direct tie to what we're going to do with acoramidis, but I think some of the experiences that our commercial team has had will stay at us in good stead there. Maybe the final piece is just coming from the national sales meeting. We have built an extraordinary team. I mean the field force is fully higher. The MSLs are fully hired. Every single one of the market access group is fully hired from the FRMs the PALs. And it's experienced team, Fred Hassan and Jennifer Cook from our Board, were out there. So I think we've got the right level of experience. We've got folks from Pfizer, folks from AZ, folks from Alnylam. We got a nice mix on the field force of people who know TTR and others who just know cardiovascular disease. And so we -- I think we're -- we will be ready to go.

So one nuance that at least I've noticed in conversations post-HELIOS-B is pre-HELIOS-B, it felt like acoramidis versus tafamidis versus vutrisiran. Now it feels like it's almost acoramidis versus the combination of tafamidis and vutrisiran are kind of ganging up on acoramidis. How do you think about navigating against that combination and how you convince specialists to kind of prescribe acoramidis as opposed to that combination?

Yes, that's a great question. I think, first and foremost, the market will evolve as a single agent market for now. And then I think orals will be -- stabilizers will be frontline. So I continue to focus on tafamidis. Obviously, when we launched tafamidis will be the only rare medicine on market for a brief period of time. In the longer term, I think combinations could be quite interesting. And when I think about it from a path a mechanistic standpoint, it's like, well, how many of those toxic monomers, to go back to your first question, are still remaining? I think a 95% stabler has -- stabilizer has 5%, still remaining. Alnylam is 81% mean max knockdown or so, it looks like. And Pfizer is a 60% stabilizer. So I actually think a 95% stabilizer, if you just do the math, does the same job, if not just slightly better on the toxic monomer population than does the combo. So we'll have to see. I mean these trials so far have not been powered to compare the combination against a single agent more potent stabilizer, but physicians will have to figure that out. In the meantime, obviously, if you can have that degree of potency with a more convenient, cheaper stabilizer, I think people will go that way.

What are your thoughts on investing in a monomer assay to really drive this point home because I guess that's one thing that we're missing in really understanding the differences across the approaches?

Yes, it's a great question. We've definitely invested in it already, which is basically an antibody, trying to identify that circulating monomer. It's nontrivial. We and others have not been able to make much progress there. The best we have, honestly, right now, is that serum TTR measure, which is admittedly noisy. But I don't think physicians across the 4 different in vitro assays necessarily feel -- it's not that they distrust it. They just don't know them. What chaotropic agent did you use on the Western blot, or how was the FPE assay designed? And I think there's been a little bit of misinformation that's been put out by one of our competitors in and around how these assays are used, et cetera. And so I think -- but if you look at every single one of those assays, if you look at the biochemistry of acoramidis, it is obviously a more potent stabilizer, sees more target as a superior KD2 has the enthalpic binding mode as compared to the entropic binding mode of tafamidis. So I think all of those things stand it in good stead. Whether that convinces physicians, I don't know, right? I think the serum TTR is where we'll have to start on that.

Okay. Got it. Well, it sound like 99% of investors are convinced that tafamidis is going generic in 2028. I think you don't quite espouse that view. What gives you the confidence that tafamidis will stay branded longer?

I mean, first and foremost, we're not necessarily interested in commenting on their patent estate. My hope is that we continue to see more accessible medicines for patients over a long period of time here. I would just observe that Eliquis was just recently defended by Pfizer, although they were guiding to a certain LOE for 5 more years. They tend to do this. They've taken price increases in the last 3 years, and they often will guide physicians and say, "well, the drugs going generic in 2026," which we already know they've defended against. So there's a little bit of posturing there, I would say. You don't run 12 clinical trials generally to defend a patent estate that goes out to 2035 and then just let it go away in 2028. More concretely, they obviously want European litigation. There's two real aspects to this, right? One is form one in the low free energy form actually occurring in the VYNDAQEL manufacturing, and it certainly is. So then you have to flip over and say, "can we challenge the validity of the 2035 patent estate?" And that's where everyone's lost. And I think Dexcel and others are effectively filing around the validity of 2035 because it's almost impossible, thermodynamically and probable to make the VYNDAQEL generic without accessing that low free energy form.

Yes, a quick question?

My brief question is push the [indiscernible], but they're not going roll -- I mean [indiscernible] [ progressive ] is a big market. They're going to [indiscernible] the detail. So what is your strategy despite the [indiscernible] with your sales force?

Can you repeat the question?

How to fight the Pfizer counter-detail?

Yes. I think it's a great question. I mean first and foremost, there's no one market that I've ever seen that where everyone responds to 1 drug. I think the strength of our data stands on its own. And I think for certain patients, a more potent stabilizer will be a value. Those patients could include earlier-stage patients that we identified. For instance, we're running a primary prevention study where if you can limit or eliminate the amount of toxic monomer that's depositing the heart over time, you might be able to access the type of survival numbers that we've been able to access, which is 80-plus percent all the way up to 100%. I think the second thing is thinking about hospitalization, where obviously we had a 50% relative risk reduction as opposed to numerically, they had none. And with the [indiscernible] correction, they had about 28%. That's going to be important for a lot of payers. It's going to be a lot of -- important for a lot of integrated delivery networks, so making that. and it's going to be really important for patients and their physicians. So I think really sticking with the data. And then the second thing is making sure that we have designed all of our programs to maximize access to our drug. Pfizer hasn't had a competitor yet. So being out there and really making sure that we're taking care of the prescribing physicians, making it as easy as possible for them to get their patients on drug and then making it very easy for patients to stay on drug, that will be important. I'm not saying that Pfizer won't also respond with those things, but those are avenues that I can see to better the field.

So maybe we can turn infigratinib. Breakthrough designation announced this morning. Congrats on that.

Thank you.

What do you think the FDA saw in terms of the differentiation versus VOXOGO that led to them assigning that status?

Yes. I mean I can just only comment on when the FDA does ascribe breakthrough designation, they see a significant improvement as compared to standard of care, which is VOXZOGO. They saw the entirety of our data set and made that conclusion. What they responded to specifically, I can't tell, but I have my ideas, obviously. We've been very pleased with both the point estimates that we've been able to drive in and around, change from baseline on average height or growth velocity for these kids, but also the early signs of impact on proportionality, I think is very heartening for the community.

What is your confidence that kind of when we have all the data to compare that the advantage of infigratinib will go beyond having an oral option as opposed to a subcu but also have clear clinical differentiation recognizing that we're comparing across trials?

Yes. I mean, that's almost the million-dollar question, right, the cross-trial comparisons are difficult. And so I think it's going to be really up to the physician community. But again, as I've said in the past, when one starts with the fact that we are addressing both of the effector pathways -- by the way, I mean, it's an interesting discussion. We probably don't have time for today, but you can look into the biology of the disease and try to understand. There are -- there is an effector pathway associated, obviously, the JAK/STAT pathway that the CMPs do not address that could actually be the reason that an FGFR inhibitor might be able to impact proportionality in a quicker and more and a greater magnitude than a downstream CMP approach. So I think it starts with, obviously, targeting this well-described condition at its source and it builds from there. The best point estimates on, I think, everything from change from baseline to responder rate to absolute AHV. And then the oral is really the cherry on top, I think.

When should we be anticipating this data? Is it likely to come 2025 or early 2026?

We have not changed our corporate guidance on that, and the '25, I think, is I think what we've guided to.

Okay. How have you kind of honed in on the optimal dose? And do you feel like there's room to continue to dose escalate maybe for those patients who need some additional catch-up growth or who for some reason, may not be as responding as well to the target dose?

Yes, it's a great question. I think for the population, we feel pretty good about the dose. The absolute AHV levels of 6 to 7 are approximating what I might expect for my own children. So it feels like we're in that range. Certainly, we had -- I think 91% of children in our Phase II exhibited some type of growth. And as we define responder rate, we were at around 75%. So there are people who are not responding. Whether or not they would benefit from a higher dose or whether they have a genetic modifier or another type of modifier that's at play, I don't know. And so it could be interesting to dose up in those situations. But by and large, for a commercial drug, we think this is the right dose because you don't want to go too high. You don't want to drive hyper growth.

Is the right time to explore potential higher doses post-approval? Or is there something sooner to be done there?

Yes. I mean there could be -- and you can see this in, I mean, mostly endocrine settings where some physicians will experiment with higher doses for non-responding kiddos or other patients in other conditions.

What's the timing for efforts in hypochondroplasia, and have you also thought about we've been going beyond into perhaps non-FGFR3-driven growth disorders?

Great question. So hypochon, I think we publicly announced that we had the first child in the run-in so that Phase II is ongoing. And in terms of other disorders, I know there's been a lot of talk about that, I think that's very interesting. For us, those start with FGFR2- or 3-driven skeletal dysplasias. Some of them are very, very severe, smaller populations. So maybe Wall Street is not as focused on them, but we certainly will be focused on them and have talked to the agency about even potentially running a basket trial there, which I think could be really neat just in terms of clinical trial design as well. Beyond that, things like Noonan syndrome or Turner and others, we have to think carefully about whether the -- I've read some notes that like CMPs could uniquely do it where FGFR inhibitors couldn't. It's obviously rubbish. But whether or not mechanistically, we'd want to come into what is otherwise a wild-type setting and inhibit it and how much inhibition would be required to drive a reasonable amount of growth, I think those are open questions. I'm going to give you an example. In the childhood oncologic settings that we have dosed this drug in, obviously, at much higher doses, we do observe elevated growth, so it is possible to do it in the context of the wild type, but how broadly we want to explore that, I think we want to be sensitive to the unmet need.

Which drug do you think is going to be bigger infigratinib or acoramidis? They're both addressing very large markets.

Agree.

They're both with multibillion-dollar revenue potential.

I think that they'll both be extremely important to the patients and kiddos that we're serving, respectively, but I think acoramidis will be larger, to be honest, because it's 13% to 15% a half [ path ]. It's very underdiagnosed right now. So I think the drug is going to be a material advance for our company and for the patients that we serve.

Maybe you could talk a little bit about encaleret. Where is that program in development for type 1 autosomal dominant hypocalcemia? Maybe can frame the unmet need for us all.

Yes, sure. So this is a first-in-class program. No competitors. So I think people are less familiar with it, but a broad unmet need, again, some 10,000 to 12,000 carriers in the United States, maybe 3,000 to 5,000 already identified patients. And what happens here is that the calcium-sensing receptor has gained a function mutations. We're going in and inhibiting it. So again, targeting a well-described condition at its source. I think we recently announced that we closed screening for the trial. So we anticipate, obviously, full enrollment right after that and then a readout next year. And in terms of what we're really focused on here because we need to build this market, de novo in large -- in many ways, sort of what Pfizer did in ATTR cardiomyopathy. The focus here is to look and try to -- and we're already doing this partner with academic institutions to look in the nonsurgical hyperpara community, for instance, and try to identify patients that are kind of hiding in plain sight. So 20% to 30% of nonsurgical hyperpara patients actually have gained a function mutations in it's CASR. So how do we bring those patients into the fold and get them genotypes so that they can avail of this drug? Should it have positive Phase III data and get approved? I think that's an important next step for us.

Yes. So you said 3,000 to 5,000 patients identified. Are those -- have those been identified by BridgeBio? Maybe you can tell us a little bit about the progress you've made ahead of what presumably will be a commercial launch? Phase II data didn't seem to leave much doubt from the efficacy profile.

It is the highest probability of technical success. I think program we have mostly because of the variance of the end point is so tight. The 3,000 to 5,000 patients is basically the number we get to, just looking across EMRs, in academic medical centers and integrated delivery networks in the U.S. alone. So those are identified ADH1 patients that I think could meaningfully benefit from the product. Yes.

And then in terms of going out to find the rest, I guess, this seems like a bit of a challenging market because the patients spread out amongst the endocrinology community. You kind of got to go in and I guess, genetically test to find the ones that would be suitable candidates. How are you thinking about approaching this unmet need commercially?

Well, the good news is that, one, calcium is easy to measure, and you can go in and actually see some of the warning signs of the low serum calcium, high urine calcium pretty quickly. And actually, like go to like the Marshfield or one of these larger networks that you wouldn't naturally associate as a maybe a medical center and find a lot of folks that wants you start looking. So I think that's the first piece. Second piece is the nonsurgical hyperpara community as well. So there are a couple of places that we can narrow down the search and then it will be broader education, which I think will be interesting. Final thing is, I mean, this AI approach, I was joking about it, but it's very powerful. KKC employed that very well in the FGF23 rickets market alongside Ultragenyx. And so there are probably ways that we could look for signatures. If you have some brain fog, if you have some tetany, if you have serum calcium levels that are a certain level, these are all things that would be in record, and then we can identify those a plausible ADH1 patients to go from there.

Are there commercial synergies with infigratinib?

There are. I mean on paper, yes, these are the same prescribing physicians in practice. Oftentimes, it's -- well, right now, actually for infigratinib, the call point is changing as we speak, really like medical geneticists and then pediatric endocrinologists. And so there should be some overlap, but it's probably not as much as it sounds like because these are hyper specialized physicians.

Maybe quickly on BBP-418 for limb girdle, I guess, sort of looking for the interim data readout next year. What is it that you're really looking to see at that in turn to really think about an accelerated approval path?

Yes. So just as a reminder, limb-girdle muscular dystrophy type 2I is the most common of the limb-girdle muscular dystrophies. It's a little bit more common or prevalent in the United States than are the Exon 51 associated Duchenne muscular dystrophy patients. So a sizable unmet need. And this is a first-in-class approach that's targeting the disease at its source, providing substrate to the loss of function enzyme, which is FKRP. And like in DMD, I think the path of mechanism is well described and the causal driver of disease, which is lack of glycosylation of this alpha-dystroglycan complex is also well understood by both the regulators, patient communities and the physician community. So that's the primary end point on accelerated approval. And our hope is we can see what we saw in Phase II, which is a meaningful increase in glycosylation of that complex. And then we'll be looking at the key secondary endpoints, which include a whole battery of functional readouts. Everything from FEV to ambulatory measures to the modified North Star test as well, and we'll be looking for a direction there. But according to the natural history of the disease, I don't think we're going to see a huge amount in that time frame. I think we'll be more looking for the impact on the causal driver of disease.

So then for those secondary endpoints, is there some kind of threshold you need to hit or not really? It's really going to be driven by showing the benefit in the glycosylated dystroglycan?

Yes. I mean that is the primary endpoint. Obviously, these things are all a conversation with the community. I mean it would be strange and deserve further discussion if the key secondary endpoint went the wrong way. We didn't see that in our Phase II, right? But if they achieve statistical significance, I'd also be very surprised. That's why we're running the longer trial. This is a nested trial design that goes out almost 3 years because that's what the natural history suggests. It's a very slowly evolving disease. So yes, first and foremost, it's still a glycosylation, but -- and then we have to look at the trends.

Well, a lot of exciting late-stage moving parts to Bridge. Unfortunately, we're out of time because it could have taken probably another 0.5 hours to 1 hour, but thanks so much for joining, and thanks, everyone, for coming up.

Thanks, Josh.