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

Good morning. I'm just going to read this disclaimer. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Good morning, Neil.

Good morning. Thanks for having me. Sorry to be a couple of minutes late.

Great. Great for you to be here again this year. And wow. That's all I can say. What an incredible year for Bridge. I know we're going to hear a lot about the development here. But it's really exciting to be on the verge of a U.S. commercial launch, and we're going to hear all about the profile. So I guess let's just start with acoramidis in terms of the profile, and I know there was some recent data that you put out at the European Society of Cardiology, and maybe we'll just start there.

Yes. Well, maybe I'll start at the top, and thank you and the team for having us here. We really appreciate the partnership through this year. And this year has been a year of pure execution for us. First and foremost, it's been preparing for the commercial launch of acoramidis. And secondly, and importantly, it has been progressing the 3 Phase IIIs. We have $1 billion plus markets that hopefully, we'll read out mid- to late next year. So probably we did talk about all of that. But for now, the focus really is on acoramidis, the launch here at the end of the year, and we're just coming out of ESC, and I'm happy that you're asking about our data because it did get a little bit overwhelmed.

Let's start there.

Yes. So it's perfect. Really the core of the presentations that we had at ESC went all the way back to the founding hypothesis in and around acoramadis and ask the question, do ever-better levels of stabilization as measured by in vivo serum TTR levels lead to better outcomes for patients. And I think you probably recall this, when we were IPO in Eidos all the way back then, the question was always, okay, we get, it's a better stabilizer, better PK, better bonding properties but does better and more incremental stabilization lead to better mortality or better outcomes for patients. And there was this [indiscernible] study in variant population that suggested that, yes, that might be true. But the attribute data set that we generated was the first time we could ask and answer that hypothesis in the wild-type population. So do ever-better levels of stabilization as measured by in vivo serum TTR lead to declining rates of mortality and improved survival? And the answer is yes, at a p-value of less than 0.001, we established the connection between ever-better levels of serum TTR and declining levels of mortality. Then the second key question that we asked was, okay, well, does acoramidis do better in terms of interrogating the higher levels of serum TTR than this tafamidis? And we have the unique ability, as do all modern trials to take patients that were on tafamidis and then in OLE actually put them on acoramadis and see whether or not they get the incline in serum TTR stabilization levels. And indeed, every individual that we placed on acoramadis coming off of tafamidis experienced a reasonably large incline in the amount of serum TTR that they had suggesting that they were available to higher levels of stabilization, which again are correlated with declining levels of mortality. So a really important data set we're excited about. And it really buttresses the earlier data where we showed in a post-hoc exploratory analysis that acoramidis drove about 42% elevated serum TTR levels as compared to tafamidis consistent with what we saw across the board in terms of acoramidis outperforming tafamidis on key biomarkers and basically everywhere we like in the trial.

Right. Well, congratulations, and it has been incredible to see the evolution of your data set and proving out the thesis that you started with. So we do -- I think we should touch on the Alnylam data that also was disclosed at ESC and the HELIOS-B data in terms of putting especially in the context of your drug.

Yes. I mean, first and foremost, I think there's a lot of excitement around having an additional therapeutic agent. I will say that the most pervasive issue that we have in the TTR marketplace is finding patients. We're at 45,000 patients diagnosed. We think there's something like 250,000 to 300,000 patients in the United States alone and every additional sponsor that comes into the marketplace, as you well know, will help drive diagnostic and disease awareness. So heartened by that, I'd say there was a clinical experiment that was run and it's always interesting to know then ask, what did we learn from that? Our hypothesis, when we started with acoramidis was that ever better levels of toxic monomer control. So the more and more you can reduce the amyloidotic precursor to what deposits in the heart, the better you should do. And therefore, 95% stabilizer should outperform a partial knockdown, 80% knockdown with Alnylam, and it should outperform the 60% stabilizer. And I think what we saw in the clinical results that were presented was the case that acoramidis still, to our knowledge, is the first molecule that separate that has impact at 3 months against the key composite endpoint of CVH and all-cause mortality. And secondly, at 30 months, the relative risk reduction of 42% is the best that we've seen and that compares very favorably to what we saw from Alnylam's data. Secondly, as I was alluding to, a key thing to do in all of these trials is to go back and look and see how monotherapy of the new investigational agent compares to tafamidis. And I think in this case, surprisingly, in my opinion, of vutrisiran and tafamidis were right on top of each other. So not a lot of differentiation there. I think we're going to have to learn more about that as things go forward. But overall, we were heartened to see outperformance of small molecule stabilizers on ACM, on CVH and importantly, on the composite endpoint, both in terms of time to separation and in terms of absolute magnitude of impact at 30 months. But cross-trial comparison, those are almost fraud. So it's kind of what we took away from that.

Right. Great. Maybe I'll stop and ask if there are any questions because, obviously, substantive data set -- yes, sir?

I guess as a bull argument running around for Alnylam about working in combination when tafamidis goes generic, that they'll price it accordingly to be competitive. What are your thoughts on that? Would you compete on price with monotherapy versus combination of tafamidis in the Alnylam drug? And will tafamidis go generic? I mean in just...

Lots of questions in that question. Our view is obviously that tafamidis will be protected out to 2035, we can go through the litany of reasons. So we believe that to be the case. But suffice it to say, let's start there. So we think it's protected out to 2035. Let's go back though then to the path of mechanism of the disease and try to explore whether or not combination is required for highly potent agents. Highly potent agents being a 95% stabilizer or if indeed, let's say, Intellia is a 90-plus percent knockdown, those types of agents. Those agents are actually reducing the amount of toxic monomer, if you will, down to effectively the proteostatic clearance rate. So whether or not you would need a combination agent or whether or not a combination agent would actually outperform the single agent in that case, I think it's yet to be determined. What we see in context of HELIOS-B, obviously, is a little -- I mean we need to see a little bit more on what the combo actually did. We need to see a little bit on the CVH curves, et cetera. But there's a hint of combination outperforming, but that certainly that's not going to be enough for payers or regulators to say that, that is what we need. I think the more interesting combinations of this space are going to be the combination of antibodies plus something that's interrogating the upstream because obviously, the antibodies will help with what's already deposited and both knockdowns and small molecule stabilizers are acting on the same toxic monomer pool. So this is how I see the space play out. Yes?

Any other questions? Great. I'm sorry. Okay. Great. So you've got a November 29 PDUFA date. Pretty exciting, but you also continue to have evolved data sets. Would you anticipate releasing any additional data before the PDUFA? Or are there any other events that we should be focused on?

Yes, one of the things that you alluded to was I've been pretty proud of the fact that we've met our goal of, I think, 25 publications coming out of a tribute within the first 18 months post getting top line data. And so HFSA, we'll have further data and AHA will have further data, and that will include long-term follow-ups as well. So yes, we anticipate continuing to publish as best as we can against the OLE as we get ready to launch.

Great. And speaking of launch, it's right around the corner. What plans have you put in place with respect to commercialization? And how should we think about the required infrastructure?

Yes, not publicly disclosing precisely how many reps we have or what is in the field. But suffice it to say, the field is now fully built. We obviously started with MSLs and the DMMs that we could call on payers and physicians in this prepromotion stage that's fairly sensitive. The field force is now fully built, we actually have our sales meeting next week.

Where?

Vegas.

Okay. There you go.

And so we'll continue to be ready to launch as early as the beginning of October. If indeed approval is to come early and then if it comes in line with expectation, we'll be ready to go. So in terms of market research, you've seen recent demand survey, which has helped with field force sizing. The field is fully hired and now being trained in terms of all the sales aids and the DTC, et cetera. We are ready to go. Our LDN is designed. We've picked our SPs. We're ready for the launch in all of those ways. And I think importantly, we're focused on programs that revolve around access. We've heard very clearly from the clinical community as well as the patient community that the ability to conveniently write a script is going to be something that either differentiates one way or the other, and we've been trying to focus on that using our sort of history in the rare disease space to bring the best of what we can to cardiologists given that this is a high-priced category.

Right. And in April, you signed an agreement with Bayer for Europe? Maybe you can touch on the regulatory status in Europe? And then what plans you have or Bayer has in terms of rollout there?

Yes. I think we publicly announced that we had filed our MAA not long after our NDA. So we anticipate approval sometime early in the year to come, in 2025 in Europe. Europe is an extremely exciting market for us given the fact that obviously, our clinical trial was biased towards Europe. It's also exciting because Teresa Coelho was there. She is the original discover of the trans repressor and there's a great number of truly expert sites there. And Bayer's, they're just a wonderful partner to us. I'd say their cardiovascular infrastructure that has some 450 FTEs already set up between Xarelto and then you saw some of their recent heart failure data at ESC as well. They have a real unique expertise around cardiovascular products and the marketing there. And so we're learning a lot from them and excited to launch alongside of them in Europe.

Great. So if we think about the current market, if you will, on the ATTR-CM, we have tafamidis that exited their second quarter approximately $6 billion run rate. I think we hear about the opportunity being in the $10 billion to $15 billion or so area, could be more as you continue to identify patients. Maybe just want to touch on the landscape there.

Yes. So primarily, what's been driving the growth, which has been quite incredible...

100%? Year-over-year?

That's pretty good. Has really been two things. One is the continued identification of new patients moved somewhere from like 35,000 identified patients to close to 50,000 now. And I expect that that's going to continue at an increased clip based on more and more people coming on to the playing field. And then the second is more people who are identified coming on to drug because obviously, although those numbers are quite large at a price point of $272,000 or somewhere north of that, we're not getting a vast majority of the 50,000 patients even identified onto drug. So a big part of that was IRA. That started to take effect this past year and will fully take effect this next year in terms of being a $2,000 copay that gets spread across the year for patients. So I expect that gap between people who are identified but cannot afford the drug and continue to narrow. And so that will drive some growth. And then I expect continued growth based on new diagnoses. And the new diagnoses, you can see quite nicely from the expanding call point. It used to be that there may be 70 or 80 centers of excellence, effectively that we're diagnosing and prescribing. And now you see hundreds of different call points and sites actually accounting for 80% of the script. So it's been a nice enlargement, and Pfizer has done a great job of driving disease awareness.

Okay. And maybe before we leave, maybe just a follow-up on the LOE because there is a little bit more detail here in terms of your view of the 2035 and there's been some activity on the IP front, Pfizer's pretty quiet about it, but maybe you want to touch on that.

Yes. I mean I think, first and foremost, we follow the European litigation and from that, I felt like Form 1 was fairly well protected. And we also feel, I would say, as a corollary, as IPD, can now point out with some probability that it's very, very difficult to make this drug either form of the drug without accessing Form 1 liquid suspension you tend to actually manufacture the low free energy form of the drug, process chemist at Pfizer have demonstrated that, and I think our own process chemists have copied data as well. So we think the 2035 patent will hold. We'll know more in about 1.5 years in the U.S. here. And then if you think about why Pfizer hasn't updated their own guidance, if you go and look at the last 3 brands that have gone generic for them, they always cite COM and then they start elongate -- I mean even around Eliquis, I think they've got another 5 years but they never updated it up and until a year before, composition and I know it's going away. So that's been a part of their track record in terms of communication, I don't read too much into the fact that they are still saying end of '28, '29, I think, ultimately, they believe that they're going to be able to protect this brand.

Great. Okay. Any other questions before we move on to infigratinib? Okay. Great. Well, maybe stepping back because obviously, you've got a broad portfolio and you've been very focused in terms of target selection. It's been very successful with acoramidis and maybe you can touch on how that's translated into infigratinib, and we can talk about that clinical trial status, too.

How targets like -- yes. I mean, generally, we try to design the optimal drug working for the marketplace backwards and working from the path of mechanism forwards, if you will. So the path to mechanism in the case of achondroplasia is well described in terms of there being a point mutation that's gain of function in FGFR3. And our observation at a biochemical level was direct inhibition at the level of the receptor or block both effector pathways, the JAK/STAT pathway and the MAPK pathway, which in predictive animal models and cellular models and now, thankfully, in the clinic, has shown that we can get better efficacy than the already existing CMP agents. So that was on the one hand. And then on the other hand, looking at the marketplace, a single daily or even single weekly injection appears to be beatable when you think about an oral, an oral that's the size of a grain of rice, could be easily mixed in with apple sauce, I mean -- and you're talking about a chronic medication that you're taking from point of diagnosis all the way until your growth plate closes. So we felt that was important. And ultimately, we felt safety was very important. Obviously, injection site reactions, CMP has come out of the hypertensive literature. We wanted to avoid all of that and we felt low dose inhibitor that targets the disease at its source would allow us to do that. And certainly, it has thus far allowed us to have that differentiated profile, both on efficacy, safety and ultimately on convenience.

Yes. Maybe you can highlight the TTP in terms of what you've shown to date from a clinic trial standpoint, and then where we sit with respect to the ongoing Phase III?

Yes. I mean I think primarily what the agency looks at is change from baseline in tight velocity. And there, we've shown point estimates going all the way out to 18 months of 2.5, which are almost double what it has been shown in the field previously. I think importantly, the community of children and parents that are affected with this condition, look at additional endpoints like proportionality where we've shown, I think, over an order of magnitude better performance with our medicine in that context. So I think that's going to be really important ultimately for our label as well in this space. So that's the type of efficacy data that we put up. And then on the safety side, the drug has been very benign for long periods of time. And then the formulation looks great.

Right. Great. So you're in the ongoing Phase III.

Yes.

When would you anticipate a data readout from that trial?

So the way the Phase III works, in very similar to the Phase II as you could establish a baseline, so you kind of know whether or not you're -- you've got the right number of folks. So we've got everyone in that observational period, if you will. So the trial will be fully enrolled this year and we'll read out sometime late next year.

Okay. Fantastic. Okay. And from your perspective, plans to commercialize that product?

Yes. I mean, I think we're going to learn a lot with the acoramidis launch. I mean it's interesting, right? We have sort of 2 archetypes of products we have, on the one hand, a competitive space. There's no more competitive space than TTR, I think, but achondroplasia might be out there. And then you've got other markets like ADH1 or LGMD2i, which we believe are quite large, but that's more going to be around patient finding and us building it since we're first-in-class medicines there. But yes, the plan for achondroplasia is to launch, and we obviously got partnership with KKC in Japan. And outside of that, we're excited to launch the product.

Great. Excellent. Any questions in infigratinib? Okay. So Neil, you mentioned ADH1 and Limb-Girdle Muscular Dystrophy 2i thought I'd read it out. So it would be great to get an update on both of those. Again in pivotal trials and maybe touch on the market opportunity, which are also significant.

Yes. So maybe I'll start with ADH1. ADH1 for those of you that aren't familiar with the condition, is a condition that uniformly stems from gain of function mutations in the calcium sensing receptor that leads to low serum calcium levels and high urine calcium levels. And what we showed in our Phase II was that we were able to drive about a 70% response in terms of full normalization of urine and serum calcium levels as opposed to standard of care, which is calcium supplementation, which was able to drive that normalization and precisely 0% in patients. So it's about the highest probability of technical success trial, I can think of running since the endpoints are serum and urine calcium, they're not a behavioral endpoint that has higher variance. In terms of patient numbers, when we look at the statistical genetic epidemiology and databases, it looks like 10,000 to 12,000 carriers in the United States alone. That's a very, very large market. Well, it's already been identified, and I think consistent with the enrollment of our trial is about 4,000 to 5,000 patients. In the U.S. if you look at the already outstanding databases. And what we've shown is it the nonsurgical hypoparathyroid population. If we start genotyping that population, we're picking up about 20% of patients within that population that actually are ADH1 patients that are sort of hiding in plain sight. So I think this will be a market building opportunity. I think you could start with the sort of baseline assumption of about 5,000 patients. But our hope is that we will identify many more of those patients that lie in the currently undiagnosed, but still carriers within the U.S. So that's on the ADH1 side. That trial is fully enrolled in terms of the screening. We have all the people we need in screening and so we would expect full enrollment sometime later this year for a readout mid next year. And then similarly, with LGMD2i again, some 7,000 to 8,000 patients alone in the United States, a devastating and debilitating disease, analogous to some of the other muscular dystrophies that you've seen, maybe a little bit larger than the exon 51 population. This one uniformly stems from loss of function in an enzyme called FKRP. And the good news is the path of mechanism all sort of conceals around lack of glycosylation of the alpha-dystroglycan complex, and that is the endpoint, the primary endpoint for our accelerated approval. And again, that trial should be reading out sometime mid next year as well.

Great. Yes. Excellent. Any questions on those programs? Okay. Well, great. You obviously have a lot going on, and you've been really creative on the financing front in terms of not only the continuing of the development of these programs, but a broader pipeline beyond. You form 2 new companies or joint ventures of BridgeBio Oncology Therapeutics and GondolaBio. Maybe you can touch on your thinking there and also the creative means on which you're financing those programs?

Yes, sure. I mean I'm proud of the way we've been able to capitalize the company over the last 1.5 years, thanks in large part to the partnership with Morgan Stanley. We've been able to add well over $1 billion to the balance sheet and to do it mostly away from equity. Sort of the point of time right now for the company is I think we've proven that we can do R&D fairly efficiently. I mean 15 INDs in less than 10 years, I think we have the ability to have 6 approved products by the time our first decade is up. So that's a really -- that's a uniquely productive engine. But investors rightfully are waiting to see whether we can commercialize. And so in that very moment, our cost of capital is quite high and investors are unable to avail of the upside that comes from our earlier stage programs. And so as we assess those opportunities and understood that there were many more opportunities to help patients and we want to go as quickly as possible for patients instead of pausing those programs, what we decided to do was to capitalize this externally so that investors of Bridge could hold on to a chunk of ownership there. But that we could continue to progress those programs forward as rapidly as possible. And I think you can see the fruits of that already. I mean, just last week, there was a beautiful nature paper in and around dual RAS inhibitors effectively being the way to go to overcome the resistance of the OFF inhibitors that were first-in-class. And so there we have it, we're in the clinic with a dual and that's all part of BridgeBio Oncology Therapeutics. But we couldn't have done it or afforded it within the context of Bridge right now.

Yes. Okay. So if we think about the overall capitalization of Bridge, I mean, how are you thinking about runway at this point in time?

We feel good about the capitalization now. I mean, really, our focus is now hitting commercialization and proving out the thesis. But we don't anticipate doing anything more on the capitalization front.

Great. So theres a lot happening through the end of 2024 through 2025. Maybe we can just -- you can summarize, please, like what you're focused on. I mean there's a lot of execution, as you mentioned both on the commercialization standpoint, the development standpoint, you've got a global organization standpoint, kind of how -- what's on your to-do list? And what are you focused on for the next 18 months, basically?

I think our observation is to do what we hope to do, which is to create a sustainable engine for patients one has to master discovery, development and ultimately, the delivery of medicines to the physicians and patients that we seek to serve. That delivery aspect is our sole focus right now. We want to commercialize acoramidis in a way that fully takes advantage of its product profile in TTR cardiomyopathy, and we want to build on that success to do this name for achondroplasia, LGMD2i and ADH1. That's really where our focus lies. And so the readout of those 3 Phase IIIs next year, coupled with hopefully a nice growth curve associated with the acoramidis launch is -- will be the -- hopefully, the readout of that success.

Well, I can imagine we'll be here next year at the same time and there'll be incredible milestones behind you and importantly, patients receiving your drug. So congratulations.

Thank you.