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

Joining us on this our second day of our 2024 Healthcare Conference in Las Vegas. For this section, I'm very pleased to host Neil Kumar, Chief Executive Officer of BridgeBio. Neil's going to walk us through some slides. And afterwards, we'll have some time for Q&A. I'll pull from the audience, but I have a few of my own in case everyone's shy. So with that, Niels, thanks so much for joining us.

Thanks so much for having me, Jason, and thanks to the whole BAML team for the opportunity to present here. I thought I'd take the first maybe 15 minutes or so, as Jason just mentioned, to sort of frame where we are as a company, and I know it's a little bit late in the conference and a little bit late in the day. So I'll shoe the normal corporate overview and actually dive right into 3 key topics that we've been getting quite a few questions about from investors. First and foremost is really how to contextualize upcoming clinical data, namely from the HELIOS-B trial, in and around the data that we presented for acoramidis and through our ATTRibute trial. So I'll spend some time there helping to contextualize at least how we see the playing field. Secondly, I'll give some updates on how we intend to communicate long-term follow-up data for our infigratinib program in the context of achondroplasia. And then finally, I want to touch a little bit on our own corporate strategy in today's marketplace and how the spin of BridgeBio Oncology Therapeutics derives from it. I'll just remind everyone that this is a highly dynamic time for the company. As everyone knows, first and foremost, our goal is the successful launch of acoramidis in the ATTR-CM marketplace. We also have 3 ongoing Phase IIIs that we believe are either best-in-class or first-in-class molecules in billion-plus-dollar marketplaces and then an ongoing Phase II in congenital adrenal hyperplasia, coupled with an earlier stage pipeline that we continue to progress. Within the context of ATTR cardiomyopathy, there's a lot of exciting data that we're publishing. We are in pre-promotion stage right now. So there's not much else we can do other than put the exciting data out associated with the ATTRibute clinical trial as well as to kick off new trials like our ACT-EARLY early prevention trial. As many of you know, we demonstrated 100% survival in an ongoing Phase III with our partners at AZ and Alexion in Japan. We published excitingly just this past weekend at ESC Heart Failure, the ACM data or mortality, exciting relative risk reductions that we were able to achieve in our ITT population of 632 patients, which were inclusive of our sickest patients and that offered a p-value of 0.04 for ACM alone. And we'll have a lot more to say about and a lot more abstracts coming up at ISA here at the end of May, which is perhaps the most important amyloid conference of the year. All of this is happening within the landscape of us diagnosing many more patients on an ongoing basis. As you saw, I said probably easily from the tafamidis quarter-on-quarter growth or the 60-plus percent annualized growth. We're finding a lot more patients, and we're getting a lot more of those patients on drug over the course of time. So that's, I think, exciting regardless of who sponsor you're talking to or what therapeutic you're speaking about. We were also able to strengthen our capital base over the course of the last several months. We've done it mostly away from equity given our lagging share price, but we've done it in partnership with some of the strong royalty debt and now pharma partners on the commercial side that we're very privileged to be working with. And then we were able to unlock some early-stage value with BridgeBio Oncology spin out, and I'll talk a little bit more about what shareholders can expect from that and other similar situations going forward. Okay. So let's spend a little bit of time on ATTR cardiomyopathy and just how we think about the ever-evolving landscape. And here, I should say, just at the outset, we are rooting and do believe that vutrisiran will come to the market. There is no one or even 2 therapies that will care adequately for the entirety of a population like this. And our belief is they have an effective and safe product that will come to the marketplace. And ultimately, our aim here is to clear up any misinformation. There's been many, many analyst notes, I think, written on this trial and what the bar should look like, and we just wanted to put forth what we believe the ATTRibute clinical data effectively suggests for how patients and physicians might view these products side by side. So if you remember anything from the presentation, this is really the key slide in terms of trying to understand what the bar is within ATTR cardiomyopathy. Really 3 numbers. The first is 42 and 3. The second is trends favoring acoramidis, and the third is 30 months. So maybe on 42 and 3. As many sponsors have us and Alnylam noted that there are many fewer deaths occurring in clinical trials today, thankfully, given the improvements in clinical care. And so the composite endpoint of all-cause mortality plus cardiovascular hospitalization is really how we think about relative risk reduction. And here, what we were able to show in the ATTRibute trial was a 42% relative reduction over the course of 30 months against that composite endpoint. And with those KM curves separating materially at 3 months and continue to separate over that course of time. So 42% relative risk reduction and a 3-month separation is really how we think about the monotherapy arm of the upcoming clinical data that will be presented. Now as many of you know, within the context of these ongoing clinical trials, what we're also able to do is to cross compare within a single trial, how we're doing against tafamidis. These trials are not designed to be double-blind head to heads. These are all post hoc exploratory analyses that are not complementary in any way, shape or form, but we obviously do get quite a few questions about how our drug versus tafamidis did in the context of the trial. We've published a bit of that data certainly in the context of NT-proBNP and serum TTR. And I think it's important to note that from a point estimate standpoint, there's nowhere in our trial where we look where acoramidis is now outperforming any other agent that was available to patients within our trial. Again, with the caveats, the very few patients were on tafamidis and they were on for a shorter period of time than they were on acoramidis. So that's going to be something that people will be looking for in the context of upcoming clinical trials, how did the population on the investigational agent compared to the population that was on tafamidis itself. And then finally, 30 months. As all of you know, these are not classic Cox proportional hazard type curves. What you see is an ever-enlarging separation, certainly, as it pertains to ACM and CVH as the trial on goes, I think Pfizer had published some very interesting data suggesting that with every 6 months of elongation, you pick up another 5 to 7 percentage points or so of relative risk reduction. And so we're going to need to go back and look at what things look like at 30 months, which I assume we will have given the time series that all sponsors are likely to publish. So those are really the first 3 things, and I'll get into a little bit more data against each of these. In the context of number one, what you can see here is, again, our KM curves as they pertain to all-cause mortality and first cardiovascular-related hospitalization. Over the course of 30 months, we have published this data. Maybe a couple of things to point out. Obviously, the separation of 3 months is something we had not seen before. The striking 42% relative risk reduction is also something that we haven't noted or at least anything of that magnitude as far as we're aware of in the space, and you can see the p-value of 0.0008, which is highly statistically significant in the context of our ATTRibute trial. I should also point out as it relates to the second point that we mentioned in terms of intra trial comparisons. We were able to look at NT-proBNP levels and serum TTR levels. And in both cases, what we were able to see was that acoramidis given its higher levels of stabilization was able to outperform those patients both on placebo or placebo plus tafamidis on clinical trial. This is data that we've already presented on the left and on the right. And then as many of you know, and we'll be publishing on and talking about at upcoming conferences, excitingly, within the OLE, we can take patients that are on another investigational agents such as tafamidis and actually put them on acoramidis and see what that does to levels of serum TTR or in vivo measure, if you will, of stabilization. And here, what you can see on this slide are that the patients that were on tafamidis and ultimately received acoramidis actually are able to avail of the higher serum TTR levels or the higher levels of stabilization that were not reached on a partial stabilizer. So that in concert with some of the data that we talked about earlier and we'll continue to publish on, which links ever higher levels of serum TTR to lower levels of mortality and hospitalization for the first time in the wild-type population that had already been published on in the variant population is a very, very exciting advance for patients. Finally, why is 30 months important? I should just remind everyone that at 30 months, we interrogated our endpoint on the basis of the FS test. That's a hierarchical analysis, very, very similar to what Pfizer used, which was also the FS test. But you can also look at another SAP, the Anderson-Gill, which does not hierarchize mortality and hospitalization. And what we were able to demonstrate again at 30 months was statistical significance against that endpoint of ACM and hospitalization. And as I mentioned at the outset, with every 5 months of -- or 6 months, I'm sorry, of increased duration, you can see another 5 to 7 percentage points of relative risk reduction potentially being picked up, and there's a wide variety of ways one can model this. But we call those the alligator jaws and they are ever increasing as you go out in duration. So that should increase the probability of technical success of any trial as you go out further in time. Okay. So what does all that mean? Obviously, we're eagerly anticipating the data from the ongoing HELIOS-B trial. We're also eagerly anticipating the largest amyloid conference of the year, which will be ISA, again held in Rochester, Minnesota, this year where we'll have more than 15 abstracts. We had set the goal to publish at least 20 different pieces of research and subpopulations and otherwise in the first 18 months post ATTRibute, and I think we're going to handily beat that goal. So we are trying to excavate as much information as possible from that data set as well as contributing new data to the field through some of our ongoing Phase IV and life cycle management trials that are kicking off, most importantly, our ACT-EARLY trial. And so we'll continue to push on that, and we also eagerly await, obviously, approval toward the end of the year as we ramp up into having a commercial presence in the AGT-RCM community. Okay. So that's basically what I wanted to say on HTRC. I'm happy to take any and all questions on that front after my comments. Let me move then to infagratinib in our achondroplasia program. At the outset of the year, we had talked about how we intended to share data as it related to PROPEL 2. PROPEL 2, as a reminder, is our ongoing Phase II clinical trial with 2 preplanned cuts one of them at 6 months and the other was at 18 months. Originally, our intent was to publish this data in a high-impact journal, if the data were positive, obviously, by the end of the year. And we still intend to do that. But given feedback from KOLs and the community that we serve here, we would also like to topline the data as soon as possible. And as soon as possible is once we're done collecting data from 18 months, which we should be in early June. And so at that topline PR, what we hope to accomplish with it is effectively 3 things. The first is the continued safety of our compound. Obviously, that's something we keep a close eye on given the population that we're trying to serve here and safety added 12 and 18 months. I think it's going to be very important to see. We obviously saw a very benign profile at 6 months and our hope is that it extends out further to 12 and 18 months. Secondly, we'd love to see continued evidence of best-in-class efficacy. I'll talk a little bit more about quantitatively what that looks like, but certainly a change from baseline. That's above what has already been established in the field at 12 months, which is a 1.35 centimeter per year change from baseline. And then finally, as many of you know, given the fact that we are targeting this disease at its source, very different than many of the other approaches in this space. And when one looks at what's possible when you both hit the MAPK effective pathway in concert with a JAK/STAT effective pathway, what we have at least seen in animal models for this condition is that one might provide in addition to impact on AHV impact on other things like spinal stenosis and proportionality. And proportionality is one of the first things that we can look at over the course of time. So our hope would be that we could see something like a trend on proportionality. We've also met with regulators, and they've told us that if we're able to see things like that as a key secondary, there would be potential for us to include that in the label, which would be very important, we believe, for this community. So the hope there is trend. Obviously, the ends are low in these trials. If we were able to hit statistical significance, that would be a big home run for us, but at the very least, we'd love to see a trend there, similar to what we saw in animal models. I'll just remind everyone of what we saw at our 6-month data set. I think most of you in the room as I can tell, are familiar with this data, but we were able to see a meaningful change from baseline in terms of AHV. That was married with a very, very high responder rate, a very, very high absolute magnitude of AHV for the patient population. It just -- recall that this is the right way to measure efficacy, which is effectively within an individual to establish their baseline and then ultimately, to look at how they do on drug, should also remind that these baselines are very similar to what's been studied in the past from some of our competing agents in terms of mean age as well as baseline. And in fact, we're probably handicapped a bit by the baseline because there's effectively an inverted parabola if you look at the Phase III data from BioMarin in terms of where you see the greatest efficacy as a function of baseline. And then importantly, for a product like this that's targeting this well-described disease at its source at a low dose, we wanted to have a look at safety. And again, at 6 months, we saw a very, very benign profile. So we'll just have to see how that plays out. So just to reiterate a little bit on the different cases that we're looking at. First and foremost, when we took on the assignment of trying to create a best-in-class therapy in this space, we had thought that an oral and safer agent as compared to what was out there in terms of CMP or CNP analogs would, first and foremost, be an important advance for patients. Obviously, in oral avoids things like injection site reactions and avoids things like hypertension associated with the CMP class. And so what we had hoped to do was to have a well-tolerated safety profile with a more convenient agent that could be sachet formulated and to meet or beat that 1.35 bar. That's obviously not our hope. Our hope is that as we target this condition added source with the FGFR3 gain of function and affecting both the effective pathways versus just 1 and 1 minimally. Our hope is that we can do something even better for patients, both in terms of safety and convenience, but also in terms of efficacy. That's certainly what we saw in the 6-month data. And so our hope is that we continue to markedly outperform the benchmark that's been put forth, which is 1.35 centimeters per year over the course of 12 months. And then as I said, aspirationally, our hope is that we start to see signs that this agent can do something beyond just growth velocity for the community that we're serving here. And those first lines we'll be looking for is in the area of proportionality. Okay. So what are the next steps? Next steps here for the overall program or full enrollment of our ongoing PROPEL 3 study, which has been enrolling quite nicely. FPI for our hypochon study, which, as we mentioned at JPM should occur well before the end of the year. And then ultimately, delivering on the full value of this program across a suite of FGFR-driven skeletal dysplasias could be FGFR2-driven, could be FGFR3-driven, but certainly, we're going to be aggressive in taking it to wherever we might be able to serve patients with the best or first-in-class medicine. Okay. With the -- a couple of minutes that I intend to talk more before I take questions, maybe I'll just briefly talk a little bit about the strategy of BridgeBio and how then the BridgeBio Oncology Therapeutic spin derives from it. And I'll just remind some of you, there's a few of you in the room that have been involved with BridgeBio since we were a private company but there's effectively only 2 equations that drive what we intend to do here as an organization. The first on the left is effectively to deliver as many drugs as possible to as many patients as possible in the shortest period of time. And so what that basically means is how many quality just in life years can we deliver to the patient communities that we serve. If we can deliver 3 drugs and optimize that, then that's great. But if we could deliver 4 in the same period of time, that's even better. And we couple that by saying that every program that we take on needs to be NPV positive and that we're trying to maximize within the concert of that first equation, overall value to shareholders. And the way to do that is obviously through a focus on ROIC, G and WACC. And these 2 things combine quite nicely. Obviously, as we take on more and more programs, our availability to drop our cost of capital through debt mechanisms and others, as you've seen us use becomes more and more possible. And so there's an interrelatedness that we've been able to take advantage of over time to serve more and more patients. The issue for that has been that over time, the marketplace and certainly with investors, we've been listening carefully to them have wanted a more focused organization, especially given the fact that even the 4 programs in our Phase III are hard to focus in on. People generally have a view that they're going to focus in either on TTR or achondroplasia, and we certainly don't get as many questions even on ADH1 or LGMD2i as we think those programs might warrant given the fact they are both in Phase III, nearly completely enrolled and set to read out next year. So the question is with an engine like ours that we think very credibly has been able to create great progress in terms of research, certainly 17 INDs in under 8 years. I think it's one of the more productive biotechs I've seen or been a part of a couple of approved products with a third on the way and generally being able to push ideas all the way to IND and less than $10 million. How do you take that capability and continue to do something special for investors when it generally looks to a lot of you in the room like burn that you're not being rewarded for. And so we explored a lot of different ways that one might actually be able to do that. For those of you in the room that were covering Genzyme back in a day, there is the availability of things like tracking stocks. We've looked at differentiated structures like an MLP structure, which is often used in oil and gas. We've looked at a variety of different types of split-offs or spin-offs and those are all effectively just variances on public market spends, investors taking concentrated bets on one or the other as you fractionate the company or privately spending something. We've done JVs in the past, as many of you know, with companies like Maze Therapeutics and we've also effectuated partnerships or asset sales. And I think amidst all of these different considerations, what we've come to the realization of is in today's marketplace, the highest and best way for us to maximize total return to shareholder while still being able to push forward important science is really the carve-out structure, meaning taking assets and spinning them private alongside a great set of syndicate investors so that ultimately, we maintain a substantial stake in that spun organization, and our investors ultimately can gain value from that stake, but that we're not financing it at BridgeBio, off of our own balance sheet. And so the first example of this is BridgeBio Oncology Therapeutics. As many of you know, we have 3 very exciting oncology assets that we've been working on almost from the origination of BridgeBio. The first is what we believe potentially a best-in-class G12C on KRAS inhibitor. The second is, I believe, a first-in-class PI3K alpha breaker mechanism and the third is a pan-KRAS inhibitor. Two of those compounds are set to go into the clinic in less than 12 months. The third just achieved development candidates, so it should be in the clinic in 12 to 15 months. And so that obviously is going to require a substantial amount of balance sheet, but it's also a very exciting time for those programs. And so what we were able to do, as some of you may have read, is to achieve a carve-out whereby we were able to partner with a wonderful group of investors to push forth that program, again, off of the BridgeBio balance sheet, but maintaining BridgeBio ownership in that company. I should say that, like everything we try to do as much research as possible to try to understand all of those different strategies, what was going to maximize total return to shareholder. And you can see here that in general, as long as these programs don't fail, something like a carve-out ultimately should be able to deliver a reasonable total return to shareholder for all of you that have been supporting the company for a long time. So with that, what's next in 2024? Obviously, the infigratinib data sometime in early June, as I mentioned, hot on the heels of that will be our Phase II data in congenital adrenal hyperplasia, late August, early September, as we mentioned at the outset of the year and then stay tuned for regulatory and trial enrollment updates on LGMD2i, a very exciting program that we believe could stand to have some more attention. Phase III enrollments on ADH1 updates and then obviously, approval for acoramidis and ATTR cardiomyopathy happening before the end of the year. So with that, maybe I'll wrap up and I guess I went a little over, but 7 minutes for questions. I'll take whatever people have on their minds.

Thank you so much, Neil. We will take questions from the audience. Don't be shy, just raise your hand. We'll get to you. Maybe to start things off on my end. You mentioned in the past, 45% or so current patients on [ Luxoco ] would likely switch to infragrotinib. What are the assumptions factored into this? And how much of that depends on that having maybe in-line efficacy, but much better administration versus best-in-class efficacy.

Yes. So we'll have to update that market research we've seen. The first bit of market research that we did that I think we had shared publicly was if we had the same efficacy but that if we were oral and safe, what would the overall share in the marketplace be and it looked like a majority share based on the profile of the 2 agents, and this was now some 2 years ago. I mean I think what patients are looking for because -- I'm sorry, what the community is looking for because the impact of these medicines compound over a period of time is differentiated efficacy, obviously, first and foremost, and the ability to stay safe and stay compliant over a long period of time since you're using the drug from diagnosis all the way until the growth plate closes. What that specific number is, I don't know, but I think it would be -- it would still be consistent with what we saw before, which is majority share if we were in line with efficacy and then it grows from there. I also will say that I do think just given the relatively smaller call point that many of the KOLs and high prescribers in this space are fairly familiar with the path of mechanism at a fairly deep level of this condition. And so the idea that you are tuning down both of the effector pathways versus 1 as long as it's situated in concert with point estimates that are much better than what we've seen before, it all kind of fits people's view that they should be a more efficacious and also safer and more convenient drug if our data hangs in there.

Perfect. Any questions? Well, let me follow up with this one. ATTR, silencers versus stabilizers, how does the market evolve? And you showed a very interesting slide a couple of weeks ago at a sell-side event. Just looking at what the Street is estimating for each of the different agents in the field. Not a lot of love for acoramidis. What's going on there? What is the Street missing?

Yes, I can't comment on what's going on there, but I may reiterate the baseline of expectation, as we understand that the market today is about a consensus 8% market share for acoramidis and about 60% for the knockdown agent known as vutrisiran. And so a majority coming in on the knockdown, a minority coming in on orals and about double of what we had or slightly over double what we had for tafamidis. I'd say as follows. First, our market research suggests that small molecule stabilizers should be first line, and that's very consistent with what you see across cardiovascular categories. I say that when we feed in the following TPP for the knockdowns that are to come, which is effectively about the same efficacy is what we were able to deliver, but obviously, with a different mechanism. And the reason I say that really goes back to the biochemistry here. Effectively, all of these agents are trying to limit the amount of toxic monomer that's depositing in the heart. And we can go into the reasons for this. You can biochemically model it or you can look at polyneuropathy data. But effectively, the same quantitative amount of knockdown is tantamount to the same amount of stabilization. So a 95% stabilizer should just outperform an 84% mean max knockdown, which should both substantially outperform a 50% stabilizer in tafamidis. And so my view, at least, is that from an efficacy standpoint, acoramidis should be able to hold its own and acoramidis and tafamidis will be battling in that first line for share. And then for those patients that are not responding and the good news here is you have things like NT-proBNP that can be used to determine who is not responding and who is responding they would then move on I would think to an orthogonal mechanism like a knockdown. And so if you play all that out, our best guess is that we're at 25% to 30% market share, something similar, slightly lower than what tafamidis achieves because usually, it's hard to displace a first mover and then the remainder would go to the knockdown agents. Yes. And the piece around safety, I think, is also an important piece here where small molecules obviously are able to spare the tetramer, the tetramer's around for everyone. There's no one who doesn't have it or has a half dose of it. You had to take vitamin A supplementation, [indiscernible] still moving to the eye. So if you could do everything that you want to do with a small molecule for reasons of convenience, cost and safety, I think you'd start there. And then for the nonresponders, move to the knockdown. So that is what informs our idea of the market and then the market research suggests something similar.

Great. Any questions? Please?

[indiscernible] And then separately, are you kind of still collecting data right now that your topline or share in early June? And if so, or you want the data at this point?