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

All right. Let's go ahead and get started. So this is a Monday afternoon of the 41st Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Malcolm Kuno and Priyanka Grover from the team. Our next presenting company is BridgeBio and presenting on behalf of the company, we have CEO, Neil Kumar. Neil.

Thanks, Anupam, and thanks to Phil and the JPMorgan team for having us back to present here. Thanks, everyone, here for [ bringing ] the tough weather and for those listening in. I'm going to spend the next 20 minutes or so talking about BridgeBio Pharma, a company that aspires to be a leader in the area of genetic medicine. We arrived here at the beginning of 2023, once again at the doorstep of profound advancement both for the patients that we serve as well as for investors, most notably due to 2 key readouts we have upcoming in the first half of this year, the first in achondroplasia and the second in ATTR cardiomyopathy. We arrived at this doorstep, having learned some tough and difficult lessons last year in 2022. We are a leaner, more focused, well-capitalized and more advanced company than we ever have been before. Over the course of the first 5 minutes in my talk, I'll talk about what all that gives us in terms of a 5-year vision. And then I'll spend the remainder of my time focusing in on those 2 key readouts. The first part of the talk will answer why BridgeBio, the second half of the talk, hopefully, why BridgeBio now. So just as a reminder, BridgeBio is an engine that sits atop the profound advances that are occurring every year in human clinical genetics. We seek to translate those advances into first preclinical programs, then clinical programs and ultimately into commercial products over time. Employing this engine over 7 years allows us to articulate what we call our R3 5-year vision. It's a bold vision that we think if we're able to hue to, will establish us as the next leading genetic medicines player that is product-focused. The first R and the most important R is revenue. Revenue, we think, is a good proxy for the number and quality of meaningful medicines that we can deliver to the marketplace over time. And here, our aspiration is an annualized run rate of $2 billion of revenue within 5 years. The second arm, which underpins revenue is readouts and most importantly, Phase III readouts. Our expectation based on the already assembled pipeline that we have is 8 Phase III readouts over the coming 5 years, 5 of those readouts occurring in markets that are $1 billion or more in size. And then the final R, which really enlivens our company and has from the get-go is research. Our aspiration here is the provision of 1 to 2 INDs per year, as always, cutting across therapeutic areas, modalities and approaches but always with an eye toward establishing best or first-in-class molecules in genetic medicine markets. The reason that we can aspire to this vision is because of the team, I'm very privileged to be working with just a subset of them listed on this slide here, 2 things stand out to me. The first is the quality of drugs that this team has created both at BridgeBio and before in their careers. We are a team that's really focused on meaningful impact as described by drugs that are approved. And the second is the persistence of this team. As many of you know, I've been presenting here for some 6 years and the phases on this slide hasn't changed much over that course of time. The second key ingredient associated with our 5-year vision as our late-stage product pipeline. This is an already assembled pipeline here of 5 key value drivers. And I won't go through each of them. I don't have time today. But what you can see is on a risk-adjusted basis by 2030, we expect to provide over $2 billion of revenue. And that's not even to mention potential M&A that we might engage in, which would obviously be focused on the late stages or on commercial products. Luckily, we don't have to wait until 2030 to see significant value inflection for the firm. In fact, 2023, as I mentioned at the outset, is going to be a very important year for the company. I won't have time to get into the entirety of the 12-month catalyst map as listed here. But the 2 key catalyst readouts will be our ATTR-CM program as well as our achondroplasia program, the latter of which we expect in the first week of March, the former of which we expect early July. As a reminder, we're well capitalized to get through the entirety of this catalyst map and into mid- to late 2024, some $550 million plus on the balance sheet right now. And with the exception of the Japanese geography associated with Acoramidis, whole ownership of those 5 value-driving assets allowing for flexibility in financing potentially either through royalties or pharma partnerships. All right. So that's the vision, and I want to now get into the first and probably most prominent of our catalyst for the year, which is that against our ATTR cardiomyopathy program, a Phase III, again, that we expect to read out sometime in early July. And I want to touch on 3 simple themes today. The first is that this is a large, growing and durable marketplace in which there's room for many winners. The second is that within this large growing and durable marketplace, we expect to provide a best-in-class stabilizer that both preclinically and clinically has established itself as a 2x more potent molecule than the existing stabilizer in the marketplace tafamidis. And then finally, I want to talk a little bit about our ongoing Phase III trials, Fidelity and what the expectation set should be based on an updated standard of care and our advantage molecule? What should we expect in early July? As a reminder, and I think many of you know this, the ATTR cardiomyopathy market is already $3.1 billion large, growing at above a 65% CAGR. Many of the tailwinds would be familiar to most people in this room. It's a very, very large marketplace, some couple of hundred thousand patients alone in the U.S. are hiding within the heart failure with preserved ejection fraction community -- diagnosis is quite easy and awareness has been spreading. I think the aspect of the market that is less well appreciated in terms of growth is likely access tafamidis at trending toward $3 billion-plus alone is still not available in some of the larger marketplaces across the world, including the United Kingdom, for instance. And furthermore, within the United States, 25% to 50% of scripts associated with tafamidis don't get filled because it's a [ Medi-D ] medicine and the co-pay is about $13,800. That goes away with the Inflation Reduction Act over the course of the next 2 years. That co-pay moving from $13,800 to something like $2,100, we believe could double the market alone in the U.S. over the coming 24 months. So overall, we believe this market is a $10 billion to $15 billion market. And within that marketplace, our desire is to create a potential best-in-class medicine. And to do so, we really hue to 2 design principles. The first of which was to maximize TTR stabilization. There are several strains of evidence that suggests why one should do this. Probably the most profound is the ATTRACT trial itself, where 80-mg tafamidis, which is about a 50% stabilizer, outperformed 20 mg tafamidis, which is about a 35% stabilizer or so. The second is all other things being equal to preserve circulating tetramer of transthyretin. No human that we know of haploinsufficient or [ null ] for this protein, and it's kept around in the human body and all species bodies at a high metabolic cost. Over the course of the last 5 years or so, we've demonstrated both preclinically and clinically, the higher degree of potency associated with our stabilizer here, you can see several different assays that assert that we're about 100% or twofold better stabilizer. Acoramidis has been shown to be a better stabilizer both in our hands and indeed in labs affiliated with Pfizer's hands. There's no publication out there that includes albumin that shows that we're not a superior stabilizer. And most importantly, the reason for that advanced stability has been well articulated. It's threefold. One, we see more target because we're less albumin bound. Two, we bind more target, primarily that second binding side of the tetramer. And third, upon binding, utilizing the enthalpic binding mode, we do a better job of pulling the tetramer together. We've shown this material advantage clinically as well. You can't measure the actual toxic monomer production in the clinic, but what you can measure are serum TTR levels, some 30% to 50% advantages over what's been measured with tafamidis in the clinic to date with serum TTR. And you can see that advantage extend to probably the most important univariate predictor of mortality in this space, which is NT-proBNP. Here, you can see measurements of NT-proBNP at 30 months in our Phase II OLE, which is a very sick patient population, actually maybe a little bit more sick than the ATTRACT population itself with some 68% of patients actually driving improvement against this key predictive biomarker. A recent publication just about a week ago showed that tafamidis at that 30-month time point in ATTRACT provided that to only 24% of their patients. So across the diaspora measurements that we can make related to stability against TTR, we can see outperformance for our molecule. All right. So how are we interrogating this potentially best-in-class molecule in a Phase III? Just as a reminder, we have an ongoing clinical trial against which we have 2 key endpoints, the first of which we read out at the end of last year, 6-minute walk distance, the second of which is going to read out in early July, which is a hierarchical composite of mortality and cardiovascular hospitalization. As a reminder, we didn't achieve our primary endpoint at the end of last year against the 6-minute walk distance because we saw no material decrease in 6-minute walk for the placebo population. Wherever there was a decrease, Importantly, we saw statistically significant impacts of the drug. That started with stabilization, moved to NT-proBNP, -- we saw it in [ serum ] TTR. We saw it in quality of life. We saw it importantly wherever we saw a decline in subpopulations for a 6-minute walk distance like the variant subpopulation. And intriguingly, we saw a 27% reduction in AE driven death as well. So all signs were that this drug was safe, biochemically active and doing what we wanted to do, but there was no material decline in the placebo. Over time, we've asked ourselves as to why that might have occurred and how we might update our expectations against what we expect to see coming out of Part B when we look at mortality and hospitalization. This slide speaks to how the standard of care has changed for patients over the course of the decade since we ran the ATTRACT trial. I think the first 2 panels have been well described and are going to be familiar to many of you in the room. There's no question that we're picking up patients earlier, and we're doing it with greater ease as we've moved from an invasive to a noninvasive diagnostic algorithm. I think most important is the third panel here, which suggests that given heavier use of diuretics and the fact that we're not putting patients on medicines that are actually counter-indicated like rhythm control medicines because we're identifying them as ATTR cardiomyopathy patients and not just run-of-the-mill heart failure patients. A patient with the exact same baseline today will die less and go to the hospital less over the course of time. And therefore, the standard of care has fundamentally shifted over the course of the last decade. This is not surprising for those of you that have seen cardiovascular markets evolve over time, but I think it's well worth keeping in mind. Another way to think about it is that the bar for demonstrating efficacy, and you can see this from ATTRibute Part A, you can also see this from APOLLO-B and several of the observational studies that have been run over the last 12 months has effectively increased or that the patient populations have been left shifted in time, meaning at any given time, let's say, 30 months to families would have had the amount in the ATTRACT trial a certain amount of decrease in 6-minute walk distance or a certain amount of decrease in terms of number of people alive, we're going to see something that's fundamentally less than that or less shifted in time. The implications of this are that we believe our drug still has a great chance of showing efficacy against the endpoint of mortality and CV hospitalization but that we're going to need to look at an overall survival where patients live longer and an overall hospitalization rate where patients access the hospital less. And the reason that we think we're going to be able to see that is partly listed on this slide here, where the ongoing fidelity of our trial continues to be very strong. We're seeing low discontinuation rates, extremely low tafamidis drop-in rates, -- and ultimately, our over enrollment going from 510 to about 632 patients provides us with adequate powering, we believe, to resolve the effect of acoramidis against the totality of evidence at the end. And what does that totality of evidence look like in terms of what are our expectations. First and foremost, we need to outperform tafamidis and all competitors on the win ratio. This is the primary endpoint, and it is the constellation of endpoints going from mortality to morbidity that we'll be measuring at 30 months. Secondly, we believe that survival needs to come in at 80% or more over 30 months. We've never seen that before in the TTR space, either on tafamidis as far as we know or in observational trials, we believe that could be possible with a highly stabilizer like ours. We believe that there's room to improve the hospitalization risk reduction that was demonstrated by tafamidis. And ultimately, we need to provide a favorable and safe profile in terms of our drug as well as ease of access. A reminder that in a $10 billion to $15 billion market, there's room for many different players to succeed. Our feeling is with a highly potent stabilizer that demonstrates this constellation of data that we would be able to pick up between 30% and 50% share and with a highly advanced as ratio even more, that is what our market research suggests. So that's ATTR cardiomyopathy and maybe I'll spend the remaining 5 minutes or so on the first of our value inflection points here associated with achondroplasia. And I'll hit on 3 key themes here as well, something similar in terms of the first theme, which is this is a large and growing market. I think one of the things people don't appreciate as much about this market are the immediate adjacencies and hypochondroplasia that are perhaps just as large as achondroplasia -- touch on that in a moment. I'll remind everyone that we have designed what we believe is a best-in-class profile, both in terms of efficacy and in terms of ROA. Our route of administration is a single daily oral medicine, which stands in contrast to the single daily injections that are currently being provided by BioMarin. And then finally, I'll just review how we measure efficacy in this space and what our expectations are from our fifth cohort in our proof-of-concept trial that should read out again first week of March or within 2 weeks, either earlier or later than that. Starting with the total addressable market. I think many folks in the room understand that achondroplasia itself was about a $2.5 billion market. I'll remind everyone of the Voxzogo launch on the next slide, but a large market affecting some 55,000 folks with about 7,000 to 10,000 treatable children being affected by this condition. Hypochondroplasia or what was historically called idiopathic short stature is another disease that's also FGFR3 driven. It's driven by a different point mutation that activates FGFR3. But nevertheless, another very large opportunity with several thousand people affected in about a $2 billion total addressable market there that both BioMarin and ourselves are exploring. And then there are some more severe scale dysplasias that are FGFR-driven accounting for a total addressable market of some $5-plus billion. So another very, very large genetic disease market. Within that context, you can see the Voxzogo or Vosoritide launch going very well to date. Obviously, it's just been a few quarters, but consensus analysts really have growth eventually peeking out at around 2.5% or a little bit over that $1 billion within the achondroplastic condition alone. And there seems to be a great deal of enthusiasm and awareness, both amongst [ peace endos ] and genetics for new treatment algorithms here. Within this space, our goals were twofold, really. Number one was to maximize efficacy. The way we thought about maximizing efficacy was doing what we always do with every disease, which is to target the disease at its source. The existing competing therapies only tamp down 1 of 2 effector pathways that are turned on when you have a gain of function mutation in this space, and I'll walk through just exactly what that looks like. Our goal was to inhibit all necessary effector pathways to normalize their action, therefore, providing best-in-class efficacy. The second piece was to avoid injections. As I mentioned, the ROA for our competition today is a once-daily injection. When we actually go out and do market research, even if we provided equivalent efficacy, almost 70% of skip preference would go towards a single daily oral versus a single daily injection. Recall that these are chronic administrative medicines that you have to actually use from treatment all the way until your growth [ plate ] closes. A reminder of the path of mechanism of disease here. This is one of the most monogenic of all monogenic diseases, meaning the same point mutation, G380R is at play in almost 90% of achondroplasia patients. It turns up 2 effector pathways, the MAPK signaling pathway as well as the JAK/STAT pathway that in turn affect chondrocyte differentiation and proliferation. And what we're doing again is targeting this disease at its source, taking that up regulated signaling and normalizing it. We believe this stands in contrast to our competitors where -- who are using CMPs to basically tap down the MAPK signaling pathway alone. In preclinical studies, we've shown that not only can we affect both of those effector pathways and normalize them, but that translates into better phenotypic resolution in the context of a preclinical mouse model that's been shown to be faithful in this achondroplasia condition alone, we can see 4x to 5x elevated bone growth as well as impact on femur length and L4-L6, hearteningly suggesting that we may have impact if we're able to dose early enough on the constellation of symptomatology that many of these children and families care about like spinal stenosis, proportionality and the like. We've been evaluating this compound in the context of our PROPEL study. We started at extremely low doses to ensure that this drug was safe. And in our fourth cohort started to approach AUC levels whereby we thought we would start to be able to see some efficacy and we are currently in a fifth cohort, which is double the dose of our fourth cohort where we expect to see differential efficacy against what BioMarin was able to put up in the past. And that, again, is the cohort that we'll be reading out in March 2023 with between 10 and 15 patients. A reminder of what we saw alone in the fourth cohort, which was against baseline and elevation in AHV of 1.52 centimeters per year, that compares to 1.35 or so of what BioMarin delivered in their Phase III clinical trial, a 64% responder rate since AHV can be sensitive to outliers. A responder rate is defined as people who are growing at 25% or more effectively coming off of one growth quartile and moving to the next of about 68%. That compares favorably to about 50% in what BioMarin was able to deliver on their Phase III, well tolerated with no hyper-fast whatsoever observed in Cohort 4 and none observed to date in Cohort 5 and a statistically significant increase in the key biomarker here of bone turnover, which is Collagen10. And so what are we looking for in the fifth cohort as it reads out? Well, first and foremost, we're looking for a continued development in AHV, our goal, even though AHV is quite variable, is that we could provide something around 1.52% or better, again, suggesting potential best-in-class efficacy within this space and meaningful improvements for patients. We'll be looking at efficacy across at least 3 measures: the responder rate that I mentioned, the change from baseline. And finally, our hope is, although we haven't been able to demonstrate it to date in the fourth cohort nor has any of our competitors being able to demonstrate this. The ability to move children into a normal growth range. The 99th percentile or so of growth for achondroplastic children is about 6, 6.5 centimeters per year. If we can get into that 7 to 9 range, we would be heartened and hope for a catch-up growth would be upon us. So those are the goals for our fifth cohort. And again, we look forward to announcing that data sometime towards the end of this quarter. I'll end by just a little bit of market research, alluding to what I was talking to earlier, which is even if we put up similar efficacy numbers to BioMarin, we would expect that we would get a lot of script preference just based on the ROA as long as we were safe for the single daily oral that could be mixed in with children's food versus a single daily injection -- and I can see that I've run over time. So maybe I'll just quickly stop on the remainder of the pipeline that I don't have time to address today. These are the other programs that we have ongoing in our late-stage pipeline. We have an AAV program for congenial genal hyperplasia, where we expect to announce Phase II data mid this year. We have an ADH1 program, where we recently announced FPI in our Phase III. We expect that Phase III to read out late this year, early next year, and we have a program for limb-girdle muscular dystrophy 2i that will begin as Phase III mid this year as well. So on top of all of the activity that I have listed here, 2 major milestones for the company this year, well capitalized to get through it. And with that, I'll take any questions.

Thanks, Neil. So there will be microphone runners. If you want to ask a question, just raise your hand. And if you want to submit a question via the digital portal, you can do that as well, and I'm happy to ask on your behalf. We have actually got a bunch of questions in the portal, so let me ask them here. Can you provide us with an update on the death rate in ATTRibute CM and how that's currently tracking for acoramidis relative to your expectations?

Yes. Good question. So -- what's -- the question -- should I repeat the question?

No. You got…

So the death rate so far was about 3.5 months to go on a blinded basis are around 20% in our trial. The expectation from what we've seen and observed cohorts with updated standards of care is between 25% to 30% death rates in the context of wild-type patients. And so we think this is tracking to the type of death that you are seeing with the updated standard of care, but certainly well below the death rates that one would see a decade ago in the ATTRACT trial, which, as you recall, at least on placebo was around 40% and on drug was 30%. So I think that is enough in our eyes, enough of a diminution for the drug to show signal, but certainly it's going to be a higher bar, as I mentioned, or less shifted in time as compared to ATTRACT.

So when -- as a follow-up question, is it basically that you're tracking all deaths or just the ones that are deemed treatment emergent. If a patient comes off therapy in dilator, would they be counted as part of the death rate that you've been reporting?

Yes, they would. And yes, it's a good question. I mean we're only tracking what we have measured to date. There's obviously -- these things can change in terms of people who discontinue. And then at the end of the trial, you go back and you try to find everyone who's discontinued and ascertain whether or not they have passed. So we have some fraction of those patients within that blinded rate, but not the entirety. It's not just AE driven death though. I think maybe is that what the question you're referring to. It's not just AE driven death, no because that was obviously all we could see in an unblinded fashion on a blinded base if we can see more.

Questions from the audience? One more from the portal, which is, given that Pfizer is well entrenched in the ATTR market with a once daily, how do you differentiate yourself and maximize your market opportunity?

Yes, it's a great question. And I go back to that market research slide, I think, first and foremost, it starts with the win ratio. I think we need to do at or better than Pfizer in terms of the constellation of impact we have on mortality and morbidity as measured by CV hospitalization. I think secondly, the absolute amount of survival that we see on drug needs to be superior. Physicians ultimately are concerned here with people living longer and going to the hospital less. So I think we need to show that on a treatment basis. And I think the third, which I just alluded to, is hospitalization. I don't think the once-daily versus twice-daily is going to be a big deal of many of these patients are already on twice daily therapies. So ROA, I don't think will be a massive differentiator here. I think ultimately, it will be -- if the story holds together, meaning we see impact on differential impact on stabilization, serum TTR, NT-proBNP, hospitalization and ultimately, people are doing less out of 30 months on the drug.

Neil, you talked about the expenses here in the U.S. for tafamidis and the out-of-pocket payment and things like that. But I was wondering if you could expand on that maybe globally. Does tafamidis have some of the same issues globally for underpenetration because of access?

It does in the sense that it's not accessible right now in some of the main markets. It doesn't in the sense that no other marketplace that I know of has such a high barrier to treatment in terms of co-pay. So for instance, Germany, France, Spain, when it does get on in the U.K., there won't be a barrier associated with high copay as you see in the States. But again, that barrier is likely to go away over the course of the next -- not likely, it will go away because of the Inflation Reduction Act. I think that there are other dynamics at play in the U.S. that aren't at play internationally that many of you are familiar with. For instance, the 340B pricing that would be associated with some of our competitors and the specialty pharmacy ownership of some of the academic medical centers changes the economics for each script within the U.S. in a way that you wouldn't see, say, in the U.K., French or German systems. So there are vagaries that will affect relative share. But yes, I mean there's no European system. I know that has a $14,000 co-pays for a drug like this.