Thank you, everyone, for joining us here on our second day of the 2025 Bank of America Healthcare Conference here in Las Vegas. My name is Jason Zemansky. I'm one of the mid-cap analysts here at the bank, and I'm very pleased to have with me on stage right now Dr. Tom Trimarchi, President and CFO of BridgeBio. Tom, thanks for joining us.
Thank you, Jason, for having us, and thank you to the entire Bank of America team for another great year in Vegas. We're thrilled to be here and looking forward to the conversation here.
Perfect. Maybe just to start broadly with BridgeBio's portfolio, I mean, especially for those who may not be as familiar with the story, could you briefly describe your approach to drug development as well as the late-stage pipeline?
Yeah, sure. I would say the best way to answer that question would be to start with our objective function, which has been the same, you know, almost 10 years in now, with that objective function being patient impact through sustainable value creation. What do we mean by that? On the patient impact side, our goal is to deliver benefit for as many patients as we can in the shortest amount of time as possible, right? Maximize impact to patients. On the sustainable value creation side, we try to do this always in a way that's NPV positive and always in a way that targets beautiful science and always in a way that delivers best or first-in-class medicine. How do you do that? We've done a couple of different things that are slightly different from what you typically see at biotech.
First, we've employed a decentralized operating model, right, where you have highly focused, highly incentived, almost like biotechs within a biotech. I think that has contributed to our efficiency, our focus, and what I think we can say now has been, you know, outperformance against any industry benchmark in terms of efficiency and probability of success. We've also taken the approach, or I've always had the view that, you know, biopharma is kind of a lottery-ticking industry. To think that you can focus on one R&D project, especially an early and risky one, and expect it to just work out is kind of a naive way to think of things.
We had a broad portfolio at one point, and from that broad portfolio came the late-stage pipeline, Attruby kind of the opportunity set that we have in front of us over the next several years, which is, I think, pretty unique just in terms of the size and, you know, scale of the ATTR-CM market. You know, we've seen some great early momentum from Attruby so far, but also the concentration of phase III readouts coming right behind that is kind of unusual, right, with achondroplasia, ADH1, and LGMD2I all coming the next year. Really exciting moment for the company, a lot to look forward to over the next couple of years.
Got it. Makes sense. Shifting gears to acoramidis, your stabilizer for ATTR-CM, approved last November. Last month, you reported first quarter revenues of $37 million. This is the first full quarter following approval, blew away expectations. I mean, qualitatively, can you discuss how the early launch has been relative to your expectations?
Yeah. I think it's exceeding even our expectations internally, and I think there's a couple of things to kind of call out as potential explanations here. First, you know, I want to call attention to the really fantastic commercial organization team under Matt Outten's leadership. I think we really have kind of, you know, best-in-class kind of team, top to bottom, leaders, functional leaders, all the way to people in the field. Really privileged to work with such a wonderful group of executors there. We also have the clinical data package that I think is really resonating with the community, with physicians, with patients, right? 3- 42- 50, right? Very simple message. Onset of action, separation of the outcome scores by three months. That's much better than anything in the space. Reduction of composite outcome events by 42% and reduction of hospitalizations by 50%.
You know, you can get activity fast, and you can get large benefits by staying on this drug for a long time and hopefully living much longer and much better than you otherwise would. It is the team, the data package, but also this is really, I think, a market that is much bigger than certainly the street appreciates, right? We see $15 billion-$20 billion at peak. I think we are in the early innings there. We have got a great product, great team, and really a great and exciting opportunity in ATTR-CM to do a lot of good for patients.
Got it. I'm sure you're getting this question a lot, so let me just ask it again. Second quarter sales, you know, obviously the message is resonating. As you said, physicians, patients, there's a lot of buy-in here, but you're also cautioning about a few additional headwinds. You know, what are the puts and takes of each of these, and what should investors be thinking about as they approach, you know, your next earnings call?
Yeah. I would say we, you know, we started the year with great momentum behind this launch, you know, stronger kind of script demand than we were expecting. That continued through our fourth quarter year-end update, which we were really pleased to see. I think on the 1Q report, we were able to actually show that not only is there just demand for this drug, but we can actually navigate the reimbursement and approval process and get patients onto paid drug. Just to make it easy to get Attruby and stay on Attruby has kind of been our philosophy, right? Make everything easy along the way. I think we've done a great job there. You know, a couple of things to be aware of exiting the quarter. First, you know, we've seen great uptake across all the patient segments, right?
Variant, wild type, naive, second-liner treatment experience patients. Our focus has always been driving share in the frontline treatment naive pool because that's what's going to drive the best impact for patients and long-term value for the company. That share has been growing steadily every month. At the same time, we have had some contribution from switches off of other products. You know, a month ago or so, we held 100% share of that segment, right? As other entrants come on the field, that naturally evolves. That's one kind of moving piece. I think maybe the other things that you're talking about are some of the comments we made on the earnings call where, as we thought about kind of the net sales that we were reporting per kind of implied script, that was a pretty impressive number to a lot of people.
Just a couple of things to consider there. I think we had, I would say, a modestly better net revenue per patient or per script than we were expecting due to a few things. One, gross to net was favorable, right? These things tend to be volatile early in a launch. You had, I would say, lower use of some of the free drug support programs for uninsured or underinsured folks than what we were expecting. Also, slightly lower use of the first-month free program, which has been very popular, than probably what we were modeling. I think those things probably normalize through the course of the year. I think the most important thing here is going to be that we continue to drive share in that treatment naive first-line setting.
Got it. Makes sense. Maybe if one more on Attruby here. What do you think are the biggest sort of growth levers as you think about, you know, not only 2025, but 2026 as well, you know, especially as you pointed out, entry of new competitors here and, you know, an old stalwart in terms of Pfizer?
I would say there's two things. First, as I said before, the market is growing at a rate that most people don't really appreciate. I mean, if we think about the first quarter, what we saw, it's tafamidis flat despite a 20% rebate to the government right in the quarter. That suggests about 25% sales growth before that in a quarter where we're having great momentum, great starts for a launch. That means the market is growing very rapidly still, right? Like five, six years into the first product launch ever. We have a long way to go, right? We think there's maybe 20,000-25,000 patients on a therapy in the ATTR-CM market in the U.S. out of hundreds of thousands that have this disease, right? We'll continue to grow this market with the other sponsors in the space.
I think it's a category where you can have many winners, right? That's one piece of it. The other would be as we continue to get our message out and as we continue to get physicians familiar not only with the clinical package and the story around data differentiation, first and only near-complete stabilizer in this category, they're also going to start getting familiar with our programs, which are very generous, very easy to use. Actually, if you listen to some of these Wall Street KOL calls, you hear unsolicited positive feedback on our commercial and field teams, which is very unusual. They've done a fantastic job just making it, again, easy to get the patient on Attruby and get them to stay on it, meaning getting through reimbursement, helping them navigate any authorization they need, and being there to support them when they're uninsured, underinsured.
Yeah, I think those are the two things to watch.
Yep. Maybe a follow-up here. How much of this depends on outreach to your more community-based prescriber, you know, considering that maybe a lot of the early sales were in, you know, concentrated centers of excellence, academic institutions, you know, the prescriber that usually sees the bolus of these patients?
Yeah. I would say that is changing, right? That's a very fluid situation. Five years ago, I think you're right to say this is mainly, you know, probably only in major academic centers. Even probably at launch, this was quite a concentrated call point, right, where we think something like 1,500-1,600 HCPs in the U.S. were running most of the volume. As awareness of this disease grows and as physicians and cardiologists become educated, I think you are going to see more and more community docs starting to realize they have a lot of these patients and wanting to keep them. We have been happy to see that we have had uptake and, you know, writing happening across the spectrum, right? You're seeing some of the big academic centers of excellence starting to write, which is great.
You're also seeing some first-time TTR agent prescribers using Attruby for the first time out in the community. I think we're going to continue to focus on all. Of course, there are some key centers that, you know, are really going to be crucial to winning here, which we'll remain laser-focused on.
Got it. As you mentioned earlier, this really is kind of a pivotal year for the company, not just with your first commercial launch here, but, you know, you're conducting three phase IIIs with updates expected in the next 6-12 months. Can you just sort of help us frame what these are, and then we'll delve into each of them?
Yeah, sure. As I said at the beginning, I think we're in a very unique and unusual situation as a relatively small biotech company where you've got a launch that's in a big category that I think clearly is going to be a multi-billion dollar product that seems to be going well out of the gate. We feel fortunate there. Followed quickly by a late-stage pipeline, all in very interesting markets. Some competitive, some non-competitive, but we think all billion-dollar plus opportunity. Maybe just let me quickly go through them. We can dig in. I would say next biggest TAM that we're in here is infigratinib for skeletal dysplasias, right? We see that as a $4 billion-$5 billion TAM for just the achondroplasia and hypochondroplasia opportunities alone, and there's more to do beyond that.
That's a phase III that's fully enrolled as the end of next year that's set to read out likely, you know, early part of 2026. That's an oral small molecule direct FGFR3 inhibitor. So far has demonstrated best-in-class efficacy on multiple fronts and, you know, arguably the cleanest safety profile of any agent in the space while providing importantly and critically an oral option for the communities and families and children affected by this condition versus other options, which are burdensome injections. After that, and this is not in any particular order, actually, it's like maybe investor interest, let's put it that way. Next would be ADH1, which is a small molecule, encaleret, for primary indication or first indication will be for a disease called ADH1, which is really a subset of chronic hypoparathyroidism driven by a genetic defect.
There's some 4,000-5,000 patients with a diagnosis today or suspected diagnosis that are being treated, so symptomatic. No competition. We've had remarkable mid-stage clinical data with, I think it was 79% of patients responding on serum calcium, something like 96% on urinary calcium. Importantly, almost 70% achieving normalization of both, which is our phase III primary endpoint, and that reads out later this year. Expansion opportunity there in the broader chronic hypoparathyroidism population. We have our muscular dystrophy program, our ribitol for LGMD2I, which is actually, I think it's the second or third largest subset of the limb-girdle spectrum of conditions. It's about 7,000 patients in the U.S. and Europe that have this. Well-diagnosed, very mobilized patient community. No competition really in sight. Where we've had, again, compelling mid-stage phase II data.
The story there is we're going for an accelerated approval path based on a novel biopsy-based surrogate.
Got it.
That's the long overview.
Good problem to have. Let's start with infigratinib. You know, as you mentioned, there's the established CNP class, there's an injectable class. Can you discuss what are the benefits of having an oral, particularly, you know, as you try to dose children here?
Yeah. I mean, it's hard to overstate how important this is. You know, most of us that have built the company, run the company are scientists by training. I think we underestimated how important this was when we started the program. We thought mechanism was going to be super important, and the right mechanism was going to give us the right data, which has turned out to be true. We definitely underestimated how important the oral ROA was going to be. When we do market research, we find that if you just show prescribers or families blinded profile comparable efficacy to what some of the other agents that are approved have on the label, or the one approved agent facilitator has on the label.
Similar efficacy, similar safety, but a daily injection versus a daily oral, you get 70% or more preference to use the oral in the new child with achondroplasia. That is an astounding number. We also see at least 50% that would want to switch off an injectable onto an oral. It is super important. If you have children, especially young children, you probably can start to understand why. When we started this program, I did not have any kids. I do now. I get it. The mental image of taking your child and injecting them every single day for, you know, ideally, you know, we get these therapies into children as early as possible. Like infant stages through adolescence, that is a burden, right? Every day, even weekly. We have tested this in market research as well. It tends not to matter if you have an oral option.
It's super important. And, you know, we're proud of the fact that we can deliver this benefit along with compelling clinical data and, critically here, compelling safety data.
Yeah. You bring up a good question. Does infigratinib need to beat on efficacy if administration is improved or, you know, to be best in class, do you really need to get that second piece there?
Yeah. If I look at the phase II, certainly, certainly we think we have the best efficacy. I think we're also mindful of the fact that, you know, that's a relatively small data set, right? It's 15 children. We're talking about high variance endpoints. It is entirely possible that the point estimate in the phase III is different than the point estimate in the phase II. You know, some of the effect on HV is different or muted, especially since we're going into younger children. Actually, that should be an expectation. Do we need to differentiate on efficacy to be a leader in this market? Absolutely not. I mean, the market research over and over again shows that you don't.
We're definitely hopeful and would like to see the differentiation we've seen in phase II hold up in phase III, especially if we can start to show a continued body of evidence, whether it's in the phase III or additional clinical work, you know, longer-term follow-up or whatever, benefits outside of height as we've started to show in the phase II, right, where we saw proportionality in a very short time frame, 18 months with statistical significance in a very small sample. So promising.
Cool. Has there been any pushback or concern, or do you think it's going to be a hurdle in terms of safety, just given that the class itself has historically had a lot of baggage associated with it?
That's certainly a conversation I expect we'll have with a small minority of prescribers or families. I mean, this is much more of a discussion we were having five years ago before we had any real clinical experience with the molecule in this condition. I think now you're seeing physicians and families that have experience with it that are just comfortable with the profile. I mean, it makes sense to everyone that when you're at, you know, a tenth or less of the dose that has been tried in other indications that had, you know, some side effects that you wouldn't see them. Once you can show it with clinical data, once they can see it and see it in the patients or the children with the condition, apologies, it's convincing. It's more convincing than any theoretical argument.
Makes sense. Let's shift gears again. ADH1, as you mentioned, kind of layer of importance to investors. Can you talk about what sort of, what does it mean for this patient group, you know, the 79% improvements that you're seeing, especially given kind of the lack of options and, you know, how does that translate into the overall opportunity?
Yeah. For those of you who are familiar with the chronic hypoparathyroidism kind of spectrum of conditions, this is kind of like a very, very severe genetic subset where you have a gain of function mutation in the calcium receptor that, you know, sees normal calcium levels as super high, screaming high. The body is constantly dumping calcium into the urine and driving blood calciums to a very dangerously low level. If you talk to specialists that treat hypopara, these are some of their hardest patients to manage because the usual thing you do and the only standard of care today, which is completely ineffective, is to try and get out of that dangerously low calcium level of blood by calcium and vitamin D supplementation.
Of course, given the biology of the disease and the genetic defect, you're putting loads of calcium into the system and then excreting it immediately, dumping it into the urine. The best they can do here, and these are the top experts in the world, is try and manage patients at the very low end of normal or maybe slightly below at the expense of screaming high urinary calcium levels, which everyone understands is going to destroy the kidney long term. It is a really horrible situation for the patient. There are no other therapies available. We've got a very safe, easy-to-give oral small molecule that fixes the disease at its source, normalizes that aberrant gain of function through the calcium sensing receptor, and basically, while removing standard of care, has provided normal levels of urine and serum calcium in 70% of patients that have taken it.
Everyone who's taken this drug has achieved what we see as a clinically meaningful improvement on these. To have both at the kind of FDA-accepted threshold of normal has been 70% or 69% in our phase II. Really, really, I think, compelling set of data there. What it means for the patient is you can live a normal life for the first time, not have to worry about, what am I doing to my, you know, other organs long term by taking my medicine that's going to keep me out of the hospital, and really just have a much better quality of life.
Makes sense. You've guided towards the readout of the CALIBRATE study second half of this year. I guess, what should investors look for? I mean, at what level would you say this is, you know, a good drug versus this is a drug I'm really excited about?
Like I said earlier, there is no real competitive bar here, which is kind of interesting, right? It's just we need to hit the stats thing, and we need to feel like we have enough efficacy to get this approved. What is enough efficacy to get this approved? Stats thing on the primary endpoint. We've powered the study fairly conservatively. I think a big unknown at the beginning was, this is a trial where you have one arm of patients randomized to encaleret, and they'll come off standard of care. The other arm is a parallel standard of care arm, right? There's a comparator. There was no good natural history here because the disease has not been terribly well studied. We ran a prospective observation study.
What we found, I think we read this out last year, a year and a half ago, something like that, was that in a prospective cohort of, I think, around 40-50 patients, we saw, as we were expecting, you know, something like very low single digits of patients that were able to respond for our phase III criteria on standard of care. That is very comforting. If I look at that versus the 70% we achieved on drug in the phase II, we think we are well above 90% powered here. I think if we can achieve stat SIG, we are going to have an approval package and a drug that physicians and patients are excited to use.
Great. Again, so many different balls in play here, but let's talk about FORTIFY. What does the opportunity look like in limb-girdle muscular dystrophy, you know, BBP-418?
Yeah. This is, as I said earlier, one of the more common forms of limb-girdle muscular dystrophy. It is type 2I. It is caused by a loss of function enzyme called FKRP, which is basically an enzyme cascade that adds sugar to alpha dystroglycan, which is part of the dystrophin complex. When you have this condition, you have the partial loss of function of FKRP, you have dysfunction of alpha -DG, and you get the limb-girdle phenotype. What we are doing here is a very simple kind of engineering-like solution, which is to take one of the substrates upstream of FKRP, it is a sugar alcohol called ribitol, supply it at very high concentrations, and just drive enzyme flux through the remaining FKRP activity.
What we've seen there is a pretty large magnitude of effect on the serial biopsies in patients that have taken this, where you get about a doubling of alpha -DG levels versus baseline in patients that have taken across genotypes. We've also seen some signals on some of the clinical endpoints, although, you know, these are challenging in small samples in relatively short follow-up, but I would say it's promising directionally, I would say supportive of what we'd expect to see. This is a significant patient population as far as rare diseases go. No competition, thousands diagnosed and eligible for therapy in the U.S. where there's no, there's nothing else really to compete. We see this again as a billion-dollar global opportunity.
Yep. Is there a baseline level of NSAID improvement that the community is looking for that would really be differentiating for these patients?
That is a difficult question. I don't think that is, that's a problematic endpoint. The challenge with a lot of these types of endpoints in these types of populations, and this is not limited to limb-girdle 2I or limb-girdle in general, is one, high variance on the endpoint. Two, there's an additional layer of noise added by the fact that every patient will be on a different stage of decline, a different part of, you know, their kind of trajectory. That creates a lot of issues from a statistical standpoint. What we've heard anecdotally is that, you know, patients are feeling better when they're on it and they, you know, they believe it's working. We can see an objective measure of the biology being impacted, which is pretty important here.
You know, we're hoping that, you know, all of our regulatory interactions have suggested willingness from the agency to be flexible and to allow us to tell the story of why we think alpha -DG is reasonably likely to predict downstream clinical benefit.
Fair. Maybe just to pivot a little bit, and this is the good problem-to-have question, but.
You know, a lot of those.
You have two rare disease launches potentially followed by infigratinib, all while trying to maintain the really awesome momentum in Attruby. How do you prioritize spend? You know, does it make sense at some point to partner?
Yeah. I would say we tend always, it's not going to be a very satisfying answer, but I'll give you a little more color that will be interesting for you. Our mentality always has been, we go by the better owner, right? If we think we're the better or best owner of a molecule in a territory, we will do it. If we think there's a partner that at the right price can accelerate patient impact or increase MPV of the product, we will do it. The partnership in Europe for BEYONTTRA is a great example of that, where we thought we got the capability to get in market, get reimbursement negotiated quicker than we probably would have been able to do ourselves in our partner Bayer. That was the right move for us, and the financial terms were very attractive to us.
For the next products, I think we'll have to look at it case by case. Certainly, we would like to protect U.S. because that's where significant value is for all of these products. I would also call out that the next three products are much more classic orphan-type commercial footprint, where we already have some presence, expertise, and infrastructure that we can build on. I think you'll hear more on that as we go throughout the year and get closer to launch on those.
Maybe, is there some synergy that we're not appreciating given that ATTR-CM is somewhat of a rare disease, at least, you know.
Yeah.
Right now, not.
It's not going to be, a lot of people think about synergy as like multiple products in the bag. It's not that. And that's actually, even in broader categories, is kind of like an old idea that's not really that common anymore. The synergies we will see are on the more generalizable infrastructure and capabilities, like access, for example, our amazing hub and capabilities on patient-physician support, which we have done in a very kind of rare disease-like model for Attruby, which is part of why that's been so successful, right? Because it's high-touch white glove service, which is exactly how you do it in ultra-orphan. There is definitely a baseline of capability that is leverageable across all the products.
I would say, like bigger picture on how we'll manage and prioritize spend, as we said, I think on the last earnings call, we're at a fairly stable place in terms of overall OpEx, and you should expect that to remain pretty steady throughout the year. If we're successful in all these clinical trials over time, you're going to see the R&D get replaced by sales and marketing to support those brands as they launch. If any of them are not successful, obviously, there's some savings there to be had. I think we're going to be looking to keep spend relatively flat, and then you're going to see an offset to that from gross profit from the brands, and we'll get closer and closer to self-funded.
Got it. And then maybe finally here, at what point are you concerned about distracting from the Attruby launch?
I'm not concerned with that. I mean, I think we'll have dedicated folks where that makes sense and where the, I think, specific expertise on a disease state or a biology or a call point is necessary, right? You know, I'm not worried about that.
Good stuff.
Yeah.
Dr. Trimarchi.
Thank you, Jason.
Thank you so much for joining us. Appreciate everything.