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

Welcome, everybody, to the 43rd Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Malcolm Kuno and Rati Pinge. Happy to kick off the conference today with BridgeBio. And presenting on behalf of the company, we have CEO, Neil Kumar. Neil?

All right. Well, thank you, Anupam, and thanks to Mike Gaito and the entire JPMorgan team for having us here again this year. I want to spend a majority of my time today talking about what you can expect from us in 2025, the underlying pipeline of products and, of course, the launch of Attruby. But before I do that, I wanted to take just a few minutes to talk about the achievements that the team that I'm very privileged to be operating alongside of have accomplished over the last 12 months or so. And I'll start where I often start, which is with scientific and clinical impact. Three landmark studies, all published in The New England Journal of Medicine across different but large areas of genetic disease unmet need. Our Phase II data in autosomal dominant hypocalcemia type 1, our Phase II data in achondroplasia and our Phase III data, of course, in ATTR cardiomyopathy. In 2024, this team complemented scientific and clinical impact with operational excellence. I can remember about a year ago being on this stage talking about my hope that we could fully enroll all three of our major market Phase III trials last year. About halfway through the year, we announced full enrollment of our FORTIFY trial in the context of Limb-Girdle Muscular Dystrophy Type 2i, and I'm delighted to announce this morning full enrollment of our ADH1 trial and our achondroplasia trial. The most important numbers on this slide are actually on the right-hand side, which is the total numbers of patients in each one of these trials. You can see these numbers married with the effect size we observed in our Phase II clinical trials, married again with the variance associated with the primary endpoints, and I'll go through some of those details in each one of these product loops, suggest that each one of these trials is at least 90% powered. Importantly, our trial for achondroplasia with 114 participants is the largest of such trials in the achondroplasia space, auguring well for the kids we hope to serve if indeed our drug is to have an impact in Phase III. The team added to these operational advancements with regulatory advances, RMAT designation for our gene therapy and Canavan disease, which I'll talk about in a bit, RPDD designation for our LGMD2I program and importantly, breakthrough designation for our achondroplasia program. I honestly feel like this last one was a little bit missed. BTD is obviously the conclusion that the regulatory agency arrives at when they look at your Phase II data and suggest that it is differentiated against the current standard of care. This is also the only investigational agent in achondroplasia that has received BTD as far as I know. Of course, the most important regulatory advance that we had this past year was our third approval and first major market approval of our medicine, Attruby, labeled for use in ATTR cardiomyopathy and importantly, labeled for the reduction of both cardiovascular death and cardiovascular hospitalization. This regulatory approval represents the culmination of 9 years of hard work. And actually, the last 4 slides represent what we've become known for, I believe, BridgeBio, which is a distinctive R&D engine. The three publications that I mentioned upfront add well to the some 72 publications that this group has put out over the course of the last almost decade of operating together. And the regulatory and clinical advances add well to the some 18 INDs, three approvals and scores of clinical trials that we have executed as a team together within the area of genetic disease. Nevertheless, there's always been an important question hanging over the head of BridgeBio, which is can we take that last and most important step in the biotechnology value chain and take the medicines that we work so hard to make and offer them to the patients and physicians that we serve in the context of the commercial setting. And that is why the next slide I'll present is perhaps the most important that I'll talk about today. As many of you know, in late November, we achieved regulatory approval of Attruby, and as early as December 11, we had drug product in channel and available. In the scanned few weeks since that approval, we have been overwhelmed by the enthusiasm we are hearing from patients and physicians alike within the ATTR cardiomyopathy community. 430 new patient scripts have been written for our drug product in the small number of weeks since approval. This does not include patients that are receiving free drug for life due to their enrollment in our Phase III trial, nor does it include patients that are part of either the extension of our Phase II, Phase III or who are enrolling in our ACT-EARLY trial. This early remarkable commercial momentum augurs well, we hope, for Attruby and its service of hopefully tens of thousands of patients in the years to come. I'll dimensionalize this number and put some numbers behind this number in the Attruby product loop. But before I do that, I'll just remind everyone that all of the activity over the last 5 slides is occurring within a new type of biopharmaceutical model, a decentralized model that promotes focus at the level of each disease and marries that with economies of scale centrally as well as diversification so we can shut down what isn't working and focus in areas that are working. All of this allows us to go after large NPV markets like ATTR cardiomyopathy and smaller but yet still positive NPV markets like Canavan disease. Of course, the most important manifestation of all of our operating activities and the model itself is the product pipeline. Here, you can see many of the programs I mentioned, so I'll be brief on this slide, but I'd just like to go through the entirety of the activity that's ongoing at Bridge. Obviously, our program in ATTR cardiomyopathy and stay tuned for some additional R&D programs layered in here in the coming months. Our programs in infigratinib for both achondroplasia and hypochondroplasia, our program BBP-418 for LGMD2I, encaleret for ADH1 and hypoparathyroidism, BBP-812 for Canavan disease. And then importantly, as BridgeBio shareholders, you own significant portions of two sister companies. one, BridgeBio Oncology Therapeutics, where my colleague, Eli Wallace, will be talking about some of the exciting progress there on Thursday at 10:00 a.m. Check out that talk, a quick plug for Eli there; as well as GondolaBio with some 11 programs ongoing within the context of the Mendelian disease landscape. What unites every single one of these programs is that we are targeting well-described conditions at their source with the hope to provide either best or first-in-class products to the patients and physicians that we serve. Okay. So I'd like to talk a little bit more about Attruby here. And I'll just remind everyone what you probably know already, which is that this is a large, durable and growing marketplace. In fact, maybe the #1 problem in the context of ATTR cardiomyopathy is that we haven't found and diagnosed the patients that we know are there and out there with this condition. Some 50,000 patients diagnosed today, but some 250,000 to 300,000 patients in the United States alone, given the percent of HFpEF that we know is resulting from ATTR-CM. And that doesn't even account for EU and rest of world. It's therefore no surprise that even amidst the strong launch of Attruby, you can see brand growth for Pfizer's tafamidis in December. We think there's a lot of room for a multiplicity of players within this landscape, and we believe this market tops out in the $15 billion to $20 billion range. So how do we optimally serve the patients and physicians within this community with our product? And we think the equation is quite simple as shown here. Number one, the provision of compelling clinical data; and number two, making it easy. We have studied every aspect of the patient journey and the physician journey within this landscape. And we have, as I'll detail in a few slides, tried to design an ecosystem with our partners such that any patient or physician that wants to write the script or stay on the script can in the most expeditious manner possible. Let me walk through each element here of this equation. The first is quite simple. The provision of compelling clinical data starts with three numbers: 3, 42%, 50%. As early as 3 months, we find our therapy having effect on the most important endpoint in this space, which is the combination of cardiovascular hospitalization and death. This is the earliest that we have observed any therapy having action within the ATTR-CM space. At 30 months, a 42% relative risk reduction against that very same endpoint, again, a magnitude that we have not observed with other products within this space. And finally, a 50% reduction in cardiovascular hospitalization, suggesting that Attruby might not only help people live longer, but it may help people live better lives outside of the context of the hospital. All of this is possible given the fact that we are the only small molecule stabilizer that is a near-complete stabilizer, the only small molecule that has near-complete stabilization in its label. And you can probably remember about 9 years ago, when you first let me on this stage, I was then leading a company called Eidos, and we were starting on the production of AG10, which was then known as acoramidis, which is now known as Attruby. And we didn't have much to go on at that time. Just a couple of assays and an e-mail shown here from Jeff Kelly, the inventor of tafamidis to the co-inventor of acoramidis or Attruby, Isabella Graef suggesting that tafamidis is indeed an inferior stabilizer to acoramidis. Since then, we had the Penchala papers, we had the Nelson paper showing superior selectivity -- showing superior stabilization. And all of that culminated in the data I presented on stage last year, showing that patients within the ATTRibute trial who are on tafamidis, when they switched over to acoramidis during our open-label extension, actually achieved higher levels of stabilization as measured in vivo by serum TTR levels. We then went on to correlate those higher serum TTR levels to improve survival and improved benefits associated with cardiovascular hospitalization. All of this stems from the fact that our molecule sees more target being less albumin bound, binds the target better with a superior KD2 and glues the target together better, employing an enthalpic binding mode as compared to the entropic binding mode of our competitors. But none of this biochemistry and none of the clinical data, to be honest, would matter if we couldn't allow our patients to get on drug and stay on drug when they have prescribed this product. This obviously has been a huge hurdle within this disease landscape. And here, you can see an ecosystem of design programs and partners to best help make it easy in terms of writing and staying on this drug. It starts with our free trial and our commitment that any time you get a script written in this space within 48 hours, we can have drug to your doorstep. It moves through a carefully designed distribution network that hails from our experience as rare disease operators. This does not look like any of the LDNs that you see in the context of this ecosystem to date. We're working with great partners like PANTHER and Orsini to deliver white glove service to the SPs, physicians and providers that we serve. And by the way, if you're an institutional SP and you want to keep your script, we will meet your business model where you are at. Our intent is to provide the best clinical service possible with Attruby. We're not so focused on precisely which SP gets the credit. Our patient hub through RareMed is also another extension of our white glove service. We've employed this in very small marketplaces, and we think it's truly differentiated. And where you actually need our team to be on site, we not only have our reps and MSLs, we have our FRMs, and we have a whole suite of patient access liaisons who can be at your site within 24 hours to help you overcome whatever hurdles you may be experiencing in terms of getting your script or staying compliant on your drug. And for those patients that need a little bit more help, the most generous ecosystem of patient assistant programs in ATTR cardiomyopathy today, inclusive of co-pay coverage, inclusive of the fact that we are providing free drug for life for those patients that participated in our Phase III. I'd encourage you to read more about the broad suite of our PAP programs serving the patients that we intend to serve. Making it easy and compelling clinical data has led to this extraordinary early momentum in our launch. You can see the 430 Attruby scripts that I talked about earlier. Actually, the number that impresses me most is the 248 unique prescribers. Like a couple of years ago, I was up here talking about 200 physicians really mattered in terms of 80% of the scripts in the space, went to 1,000 last year, it's maybe 1,200 now. But the fact that almost 250 people are writing our product in just a couple of weeks augurs well for a future where we'll be able to prescribe across a broad suite of both experts, community hospitals and heart failure practices, big and small experts and people who are just new to learning about ATTR cardiomyopathy. And this last number, the 77% in terms of parity coverage is absolutely bonkers for those of you that have ever been a part of a commercial launch. This is the type of number you would hope for maybe 9 to 12 months in and even then, it's pretty special. So commercial team has been doing an absolutely fabulous job of making it easy for the physicians and patients we serve. This next slide, I'll actually skip through. It's a suite of comments that actually don't come from our patients or providers. We have a lot of great feedback from them as well. But we thought it would be interesting to actually provide you with some feedback from our intermediaries, the partners that we work with, be it the payers, the pharmacists, the RNs, others that help us to offer that white glove service that I just mentioned. So I'll leave this in the deck and people can peruse it on their own account. But getting some of these e-mails has been some of the best days that I've had since we launched the product. And by the way, we've had some tough feedback too. That's great as well. That helps us to continue to optimize our launch over time. All of this is possible, thanks to an absolutely tremendous commercial team that I'm privileged to operate alongside of. You can see the leaders here. On the upper left is Matt Outten, our Chief Commercial Officer. Many of you haven't met him, but I hope and believe you will in the coming months. Matt was the co-architect of IMBRUVICA's launch a long time ago with Pharmacyclics, and he's been working with us for the last 6 years for this very day, preparing for this very day. Matt really represents the best of us. He puts patients first. He lives the value that every minute counts for the patients and the physicians that we serve, and he operates with a healthy chip on his shoulder, which is a requirement when you're a David in the field of many Goliath. As a reminder, for any providers, if any providers are listening to this talk, you can reach Matt at mo@bridgebio.com or myself at nk@bridgebio.com. Our commitment is you will get a reply within minutes, and we can have someone from our team at your site within 24 hours to help any barriers, again, you may need to overcome in terms of prescription. Okay. Last year, Anupam told me that I had way too much data in my slides, but I would be remiss not leaving the Attruby loop with a couple of pieces of new data that we're going to be publishing on and presenting at upcoming conferences. And maybe I'll start with what I believe is an exciting story that's emerging within the variant population. As many of you know, ATTR cardiomyopathy is really comprised of two separate populations, the wild-type population and the variant population that has inherited mutations. And those inherited mutations of those inherited mutations, perhaps the most important in the cardiovascular field is the so-called V122I mutation. And on the left-hand side of the slide, you can see some recent data published from our colleagues at the NAC suggesting that the prognosis for patients with the V122I mutation is much more deleterious than even those who have wild-type disease. About half of the median survival is compared to those with wild-type. We've always known that this is a more severe and extremely underserved population. The question that we wanted to ask within the context of our ATTRibute study was what kind of impact is our compound having within this subpopulation, the sickest of patients. On the right-hand side, you can see the answer to that question, a whopping 0.41 hazard ratio against the composite of all-cause mortality and CV hospitalization. That is coupled with statistical significance of less than 0.02. Again, the magnitude of this effect is the best we've observed. I think 0.69 is what I saw from the knockdown trials without statistical significance. And it is remarkable that we were able to achieve statistical significance given we only had about 60 variant patients within our trial. So profound impacts on the sickest of patients in this space, and that correlates well to some of the biochemistry that we presented on this stage years ago in terms of our differential binding mode to the V122I variant. Okay. The last piece of data that I'll reveal here in the Attruby loop is actually data that we didn't generate ourselves, but very interesting and a compelling story that's been arising over the course of the last decade or so. Recall, this disease is not a disease of the toxic tetramer. The tetramer, transthyretin is actually an important protein. You need it to see at night, you need it for a wide variety of other functions. It's a cell-essential gene in the top quartile. In old studies, it suggested that higher levels of serum TTR over time for those individuals that actually had the trans-allele trans-suppressor mutation in the absence of any variant mutation led to improved longevity, reductions in cerebrovascular disease and other types of disease. This year, a new study in 100-plus thousand patients also suggests that ever higher levels of serum TTR lead to ever better levels of survival. This was a publication in JAMA Cardiology. So again, the second design criteria with which we set out to design Attruby, which was not only to stave off the toxic monomers deposition in the heart, but to increase the levels of serum TTR have been come to be shown to be very important within this broad population. All right. With that, I'll turn to some of our other products. I don't have time to go through in detail data behind each one of our other programs. So I'll hit it at a high level, but we are around for the rest of the week to answer any and all questions one might have. And I'll turn next to our program, infigratinib that is seeking to serve folks in the hypo and achondroplasia settings. As a reminder, this suite of conditions arise solely from gain-of-function mutations in a receptor called FGFR3, and we are the only therapy that targets this well-described condition at its source by seeking to tamp down signaling of FGFR3 with an FGFR3 inhibitor, therefore, turning down both of the effector pathways that give rise to this condition, the JAK/STAT signaling pathway as well as the MAPK signaling pathway. Some almost 110,000 folks are affected by these two conditions across the U.S. and Europe. And again, our design criteria are not only to maximize efficacy in a way that current therapies cannot because they're only affecting one of the two effector pathways, but also to do so safely and with a convenient single daily oral solution versus the either once weekly or once daily injections that are provided for now. As a reminder, our Phase II data saw the largest magnitude of effect that we have observed to date within this space in terms of change from baseline in annualized height velocity, well above 3 at 6 months and 2.5 at 12 and 18 months. But hearteningly and more importantly, and consistent with mouse model experiments, an agent like this should be able to provide benefit across the broad suite of symptomatology that this community cares about. It's not just about height. It's about things like stenosis. It's about things like sudden infant death risk, and it's about things like proportionality. And as you can read in our New England Journal of Medicine paper, we are the only agent to date that has provided a profound impact on proportionality with statistical significance. As I mentioned at the outset, some 114 patients enrolled and randomized in the 2:1 study design. Last patient last visit had occurred this past year -- we anticipate last patient last visit occurring second half of this year and the trial readout to be announced shortly after that. All right. Turning then to BBP-418, our drug product for Limb-Girdle Muscular Dystrophy Type 2i. As a reminder, once again, this muscular dystrophy uniformly arising from partial loss of function mutations in an enzyme called FKRP. And we're doing something we always do, which is to target this well-described condition at its source by providing back the substrate for this enzyme, therefore, rectifying the causal driver of this disease, which is diminution of glycosylation of the alpha-dystroglycan complex or aDG, as I'll refer to it, more simply going forward. This condition affects some 7,000 patients between the U.S. and the EU. And given the aggressive time line against which this trial enrolled, it's either a hyperactivated community or the condition is more prevalent than any we give it credit for today. This is a first-in-class therapy. There is -- we are setting the bar in terms of therapy with a once-daily oral that we hope to be safe and that we hope to be efficacious. And when we think about efficacy, our Phase II data demonstrated a profound increase, again, in that causal mechanism for this pathology, which is lack of alpha-dystroglycan glycosylation. We doubled glycosylation of aDG, both in the L276I homozygous population, more than doubling it to almost 40% of wild-type and almost doubling it in the context of the compound heterozygous population. This was accompanied by profound decreases in serum CK, which, as many of you know, is a nice marker of muscle damage, some 80-plus percent decreases in CK and actually a wonderful correlation between magnitude of increase of aDG glycosylation and magnitude of decrease of CK levels circulating. And profoundly, stabilization in clinical measures that look at things like ambulatory measures or FVC and the like. Of course, that was an open-label trial. So we look forward to looking at more of this within the context of this randomized controlled trial that I'm showing here on the next page, some 112 patients enrolled very quickly, again, 2:1 randomized with the primary readout coming later this year against the primary endpoint of glycosylated aDG and that change. We'll also be looking at CK levels and, of course, trends within the clinical endpoint data. All right. Moving along to our program encaleret for ADH1 and HP. ADH1, as many of you know, is a disease that uniformly arises from gain of function mutations in the calcium-sensing receptor. And this results in two things. One is low serum calcium levels. The second are high urine calcium levels. And so the purpose of this drug product is to allosterically inhibit the gain-of-function CaSR and rectify those two suites of pathology, which ultimately lead to all of the symptoms that we see with patients. One in 25,000 people are carriers for gain-of-function mutations in the calcium-sensing receptor. That gives you about 25,000 patients across the U.S. and EU for ADH1 alone. Of course, that population has not been identified. About 3,000 to 4,000 patients have been identified today in the United States with ADH1. So this really will be a disease, not unlike ATTR cardiomyopathy of finding more and more patients as relevant tools start to come to the fore. This is a first-in-class drug product. So like in LGMD2I, we'll be setting the bar in terms of efficacy and setting the bar in terms of safety and the ROA, which in this case, again, is a convenient oral ROA. As a reminder, in our Phase II data, we were able to fully normalize serum and urine calcium levels in approximately 70% of the patients that we trialed as opposed to 0% coming from standard of care, which is obviously vitamin and calcium supplementation. The Phase III that's ongoing is detailed here, about 70 patients, again, in a 2:1 randomized structure with the primary endpoint being the exact same that we studied in our Phase II, which is normalization of blood and urine calcium levels. Okay. Last but not least, our program for gene therapy program in Canavan disease. I'm not going to represent this marketplace as a blockbuster marketplace. It isn't. We could talk about the NPV but this is one of the most important things that we do here at BridgeBio. In fact, one of the best days that I had this past year was co-teaching a course alongside one of our co-founders, Andrew Lo at MIT and alongside the family of the young child, Noa, who is the third child dosed in our Canavan disease trial. At her age, with Canavan disease, typically, she would be non-ambulatory, likely nonverbal, struggling greatly with gross motor skills. Instead, she was a bubbly wonderful young girl going to Boston Public School and a delightful dinner companion on that crisp fall day in Boston. The results of our clinical trial in Canavan disease to date are nothing short of spectacular. Again, we are targeting this well-described condition at its source, which arises from mutations in the ASPA gene, causing too much of a protein called NAA, which leads to demyelination in the brain. We have reduced levels of urine and CSF-NAA in profound ways within this patient population and improved gross motor skills against natural history and developmental skills in a way that suggests that we should be able to file this as a BLA sometime in 2026. Okay. I'll briefly touch on some of the advances in our sister companies, BridgeBio Oncology Therapeutics and GondolaBio. Again, I encourage you to go see Eli's talk on Thursday, I believe it's at 10:00 a.m. on BridgeBio Oncology Therapeutics, a suite of three really important programs here, first-in-class dual inhibitor of G12C hitting both the on-state and the off state in the clinic with some exciting early results. a first-in-class PI3K alpha breaker that disrupts the interaction between KRAS and PI3K alpha and a pan-KRAS inhibitor that should be in the clinic sometime this year. You can see Pedro in the back if you have questions on this before the Thursday talk, but really exciting suite of programs that we're excited to be stakeholders in. As well, GondolaBio here, you can see on the next page with a suite of early-stage Mendelian disease programs, mostly preclinical, targeting well-described large unmet need conditions at their source, hoping for first or best-in-class products. And importantly, a program that's moving into Phase IIa in EPP, where we believe we have best-in-class PP9 reduction, which obviously is the primary endpoint, as you've learned from Disc Medicines as well as being able to do that safely through the inhibition of ABCG2i or ABCG2, the transporter of PP9 from the red blood cell into the serum. So exciting programs there that is bridged by our shareholders, you own significant portions of, and we'll be excited to update you on the progress of these companies as they move forward. Finally, just as a reminder, these three Phase III readouts and the launch of VtrUvi all occurring within a well-capitalized company, access to about $900 million of cash today with an additional $100-plus million of milestones coming in with European and Japanese approval of Attruby in this first quarter, hopefully this year. And ultimately, the impact that we hope to have by 2030 is one where this suite of drug products is having impact -- positive impact on hundreds of thousands of patient lives. We thank you for the time, and thank you for the support to be able to execute against this vision. And with that, I'll take any questions. Thank you.

Thanks, Neil. So maybe a quick one for me. So you had the 430 scripts for Attruby as well as the 250-plus prescribers. Maybe you could dig in a little bit on those numbers and where are they coming from in terms of centers of excellence versus the community setting?

Yes. We'll have more to say about that, Anupam. I should mention that we're going to begin doing earnings calls with the first sometime in April or May this year, where we'll be able to roll out a little bit more data. But actually, surprisingly, the scripts have been pretty well spread. I think early before the launch, I would have thought they would begin with mostly the sites that we trialed at, which are mostly centers of excellence. But we've seen the "spread" across the various deciles of prescription being quite broad. And I think that honestly speaks to some of the great work that Pfizer has done in terms of activating the high-volume heart failure practices out there. Recall, there's almost 10,000 high-volume heart failure practices or practices that see reasonable numbers of HFpEF patients suggesting that they should have reasonable numbers of ATTR cardiomyopathy patients. And so it's heartening to see that type of breadth even just out of the gates.

And what's been sort of the initial marketing message from the sales team? And how do you expect that to sort of evolve over time?

Yes, great question. I think it starts with that 340, 250 that I mentioned. What I've been interested in is every minute counts for these patients because once you're diagnosed, you're typically Class II, hopefully, we get earlier and earlier. Obviously, our primary prevention trial is on track, hopefully, to drive diagnosis and therapy earlier and earlier. But today, people are diagnosed and they understand that they want to have drug action as quickly as possible. So that 3-month message is really resonating. And then the 42%, obviously, being the largest magnitude, especially given the fact that most events today are cardiovascular hospitalization, I think that's been resonating quite well. So it's really the meat and potatoes of this program since the get-go, right, near complete stabilization, 340, 250, I think we'll keep hitting those messages, and there'll be a reasonable number of patients and physicians that respond.

And then you mentioned earnings calls starting 1Q. I'm wondering what metrics should we be thinking about that you may provide the Street on a quarterly basis so we can kind of gauge the health of the Attruby launch?

Yes, great question. And I was going to ask you the same question. But I think at the highest level, we're going to start, obviously, with patients and how many scripts are being written, obviously, how many patients are we able to serve. We'll move there, from there to physicians, and we'll segment the broad landscape of physicians and talk about number of prescribers. And then finally, payer metrics. I think market access, although it's off to a great start, is going to be something that we really want to monitor closely, making sure that people who want the drug can get the drug. It's important to remember, 50,000 diagnosed, there's only 14,000, 15,000 people actually on the current commercial therapies. So a large part of this is both diagnosing new patients as well as figuring out ways to get people who need drug on drug.