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

All right. Good morning. Welcome to the BridgeBio presentation at Cowen's 40th Annual Health Care Conference. My name is CJ Zopf. I'm in biotech equity research here. So BridgeBio has assembled a portfolio of over 20 programs spanning genetic diseases, dermatology and targeted oncology with some genetic drivers as well. This sounds like a lot, but this -- the portfolio is supported by a unique structure as well as the company's strategy of jumping on science that they either have a lead on because they're willing to start earlier or because of their connections to academia that may give them some advantage there as well. Here to tell us more today, Senior Vice President at BridgeBio, Tom Trimarchi.

All right, great. Thank you. Again, Tom Trimarchi, Senior VP at BridgeBio. First, I want to thank all of you for being here in the room with us. I know it's the last day of what was a long, and hopefully, productive conference in what already feels like a long week and it's only Wednesday. But really appreciate you all being here. Before I dig into the presentation, I just want to say a few words about BridgeBio. So the company was founded about 5 years ago with the mission to discover, develop and ultimately commercialize meaningful new medicines for people with genetic diseases. Now in the last few years, as we've kind of tried to execute against that mission, we've grown a pipeline, as CJ said, of more than 20 programs, many of which started at the earlier stage of discovery and advanced all the way to Phase III. So we're pretty excited about the progress and also the growth potential we see ahead of us. And today, I'm going to spend the talk really doing a couple of things: one, I'm going to highlight the platform and the operating model; two, I'll provide some initial data and kind of insights into the fact that the model may be actually working; three, I'll give you an overview of the pipeline and actually tell you a couple of the product stories that we're particularly interested at the moment; and four, I'll close out with kind of where we're headed, and I'll walk you through the 12-, 24-month event path. Okay. So we like to start here. So as we say at BridgeBio, we are currently at day 1 in the area of genetic medicine. So on the left side of this page, we have got some recent highlights and advances that have happened in the genetic disease or genome research space. I'm not going to tick through all of those, but just to summarize it, today, we have, more than ever, an increasing understanding of human genetics, context of genetic variation, the tools available to really interrogate functional action of genetic mutations as well as an ever plummeting speed of genome sequencing and cost of genome sequencing, which allows us to really grow databases and shorten cycle time in terms of scientific discovery. I would say the last decade or 2 of research in this space has yielded some pretty impressive new therapeutic categories. So if you think about some of the recent launches in sickle cell, cystic fibrosis, et cetera, these are really breakthrough medicines. So I think today, with the toolkit we have at our disposal to study human genetics and genetic diseases, more than ever, we as an industry and we as a company at BridgeBio are poised to really accelerate the rate of discovery and development of new programs like those listed at the bottom of this page. On the right side of the slide here is really a graph that, I think, tells the story of why we're here and what we're trying to do. We understand there are approximately 7,000 monogenetic diseases known today. These, in aggregate, affect perhaps as many as 20 million, 25 million Americans in the U.S. alone, yet less than 10% of these have available therapies today. So this is really the problem we're trying to solve at BridgeBio. We aim to deliver as many first-in-class or best-in-class medicines as possible in the future to serve this patient population. Okay. So a little bit about the vision for the company, the model and the product platform. So fundamentally, we're aiming to build a leading genetic disease company at BridgeBio. And there are 5 core attributes, as we lay out on the left side of this page, that we think will help us get there. First and foremost is distinctive and early-stage asset selection. This is probably the most important thing we do. So this is about selecting the right intervention and the right disease. We've got a team of seasoned R&D professionals that focus only on this problem. We spend a lot of time upfront thinking about mechanism of disease, mechanism of action, and we only select programs to bring into our portfolio if they are very well understood genetic diseases where the biology is crystal clear and we can reduce it from a biological problem to an engineering issue. There's a couple of reasons to do this. One is because we hope to outperform an already high probability of technical success in the genetic disease space. And by focusing on mechanism early on, you can design experiments that allow you to quickly kill projects that are not working or where you lose conviction on the science. Two, when we do bring programs, as I just mentioned above, into the portfolio, we put them into the hands of what, I think, is one of the most experienced and productive teams of R&D operators in this industry. I'll touch on some of those people on the next page. But this is critical, highly focused, highly productive folks that are experienced and also willing to get their hands dirty and kind of turn the crank here. Third, we've built what we believe is an efficient corporate structure. And this is really essential to, I believe, sustainably play in the genetic disease space. That's because while there are a handful of genetic diseases that are quite common and clear blockbuster, multibillion-dollar market opportunities, many of them are quite small. And so we want to be able to serve, in a sustainable way, both these smaller patient populations and large patient populations. And I think to do that, you really need to have a lean and cost-efficient structure. The way we do that is by actually putting small, focused teams around each program when it comes into the portfolio and actually empowering them to make key decisions around the projects themselves without having to roll it up to management meetings or anything like that. So the way, I think, we do this is by maintaining a culture of nimbleness and kind of biotech-like focus at the product level, while holding a portfolio and a deep pipeline of assets that might look like something more that you'd see in a pharma or a biotech pipeline page. Four is related to that. When you do have a large portfolio, you have the willingness to fail. So this is about being introspective on the science. And when we lose conviction on a target or a mechanism, we pull the plug. We don't fund bad science. We can allocate those resources to more attractive opportunities in the portfolio. And five, again, is this culture of focus at the level of each asset and disease. Again, we create small, highly focused teams each time we bring a project into the portfolio. We incentivize them correctly so that they're essentially willing to run through walls to execute on the project. And by doing that, we enable speed and execution at each project level. So, so far, we've done this a few times. In the middle column, we're looking at the first 2 successes from our portfolio. So a subsidiary called Eidos Therapeutics, which is our TTR stabilizer called AG10. And second is an affiliate called PellePharm. These were actually 2 of our first programs, both started at early stages of discovery. Both are now on Phase III, and they've advanced rapidly in only a couple of years and not that many dollars spent. The next 2 companies that we list here, MyoKardia and GBT, these are not BridgeBio programs, clearly. But actually, they were done by the BridgeBio founding team. And actually, these look very much like the types of projects that we bring in at BridgeBio, where there's a clear genetic driver and where you can come in and target the disease directly at its source. Those both also started preclinically and have made it to the market, in the case of GBT, and all the way to Phase III in the case of MyoKardia. So beyond these first 2 projects that I talked about, we've got 18 more programs that look a lot like that, which I'll touch on a couple of ways in a minute. And on the right side is really, at a high level, the opportunity set that we have in front of us in this pipeline. We've got at least 2 clear, we think, $1 billion-plus product opportunities that are in Phase II or later, so mid- to late-stage clinical programs. That's the ATTR program with our AG10 and our FGFR inhibitor for achondroplasia. We've got 2 planned NDA submissions happening later this year. So those will be 2 product launches happening in 2021. These are admittedly smaller market opportunities, but most of the clinical risk is behind both of those programs. That's our FGFR inhibitor for cholangiocarcinoma and our MoCD Type A asset. And then beyond that, in the pipeline, we've got a lot of early and interesting potential big swings in the pipeline. We've got a KRAS program, we've got some other interesting cancer targets like GPX4 and SHP2. And then some of the largest genetic disease areas we're also playing in, including congenital adrenal hyperplasia and ophthalmology condition called Leber's hereditary optic neuropathy, which is one of the most common mitochondrial diseases. Beyond that, we're continuing to grow the clinical pipeline. We've got multiple INDs planned for this year. So that will tee up kind of the next wave of clinical POC readouts in the coming years. And we're always growing this pipeline. At JPMorgan this year, we announced 4 new programs, 2 of which are Phase II-ready and will get kicked off this year. And we plan to announce some more new programs later this year. So this slide is essentially the team. And I think this is really one of the things that's unique at BridgeBio. We've managed to collect what I consider a truly -- a world-class group of R&D professionals, and we like to bifurcate this group into 2 categories. On the top of the page is effectively our Investment Committee. So this is made up of Charles Homcy, Frank McCormick, Richard Scheller and a couple of others. These are folks that have run and operated some of the most productive R&D organizations ever in this industry, including Genentech, Millennium, Onyx, et cetera. But we don't ask them to operate anymore. What we actually have this team do is help us identify the most actionable science in the genetic disease space to bring into our portfolio. And then once it's in the portfolio, they constantly reevaluate the progress and ask, "Do we still have conviction of the target? Should we keep funding this project?" If we lose conviction, often we'll kill the project. We've done that a couple of times already. We have no interest in funding bad science. On the bottom of the page is our -- I call it our R&D operations team. These are people that have made a lot of real drugs, that are experienced but still willing to grind it out and get their hands dirty. These are folks like: Uma Sinha, our Chief Scientific Officer, who came from Global Blood; Eli Wallace, who runs our oncology business. He was previously Chief Scientific Officer at Peloton Therapeutics. Before that, he spent many years as a chemistry and scientific leader at Array BioPharma. And then Robert Zamboni, who is really a med chem legend, spent many years running chemistry at Merck Frosst. If you look at the products on the right side of the page for that group, these are some of the biggest drugs in recent years. This group collectively has been responsible for over 100 INDs and 20 NDAs, and I expect that number to go up meaningfully in the coming years here at Bridge. Okay. So let's get into kind of why this space is attractive to us and the progress so far. So one of the reasons that we have decided to focus on the genetic disease space is: a, there's a lot of unmet need and there's a lot you can do for patients; but b, this is a privileged space. And so a lot of it's -- by focusing only on genetic targets, you've taken a lot of target risk off the table. If you look on the left-most chart on this slide, you can see that if you look at industry average starting preclinical, the odds of success to get to market are 10% or less. If you look at only genetic diseases, 4x or more higher, okay? So that's purely target risk you're taking off the table, we're of course, subject still to development regulatory, market risk, et cetera. But I think we've taken a lot of the risk off the table just by focusing on this space. If you look at the performance of our first 2 programs that I mentioned earlier, I think this is -- these are a couple of examples of what you can do when you do focus on areas of unmet need and you have a good understanding of disease mechanisms. So our first 2 programs advanced from preclinical to Phase III in under 3 years for both of them. This is more than 65% faster than industry norms. So this is really, really exciting for us, and we hope to replicate that success over and over again across the portfolio. And again, these first 2 programs, over on the right, not surprisingly, if you cut out risk and time, you're going to have a great return on capital. So return on investment is more than 8x what you find for the typical biotech company. So again, more -- at a high level of the progress of this pipeline over the years, on the top of this panel, we're just looking at programs starting in 2015, when this company was started, to today. So we've grown from 1 program to 20 today. But more importantly, I think, we're not just buying and aggregating assets. We're advancing all of these to the stage gates of discovery development cycle. This is really important to us, and I think this is pretty unique, the velocity of which we've been able to advance a lot of these. Just a quick overview of the pipeline. So yes, I mean, this is a complicated slide. We've got a lot of programs, but there's a couple of points we'd like to make here. One, this is a diverse portfolio of very uncorrelated programs that each go after a genetic disease. You've got good diversification of weight. So our latest-stage program is already in the regulatory stages. We've started filing the IND already. We've got a couple of Phase IIIs. We've got a good collection of mid-stage programs that will be teeing up proof of concept readouts over the next couple of years. And then we've got a lot of early discovery and programs that are about to go into the clinic. So it's really good mix of late and early here in the portfolio. Another point I'd like to make is that although we are in a diverse set of therapeutic areas, again, there is really one underlying theme or therapeutic hypothesis that supports each of these programs. So that is if we can go after diseases with really well-defined genetics and where we understand the biology going from genetic driver, to cell biology, to signaling, to -- all the way to patient symptoms, that will be a space that should be high probability of success and where we can deliver something really meaningful to patients at the end of the day. Yes. So the third point I'd make here is we get asked a lot, "How do I value Bridge?" That's a good question. I think what you should do is just sum up NPV of each one of these, but I recognize that's a lot of work. So we like to bucket these into kind of business units. So we dimensionalize this into 4 business units. Our Mendelian kind of bucket, it's more of a pure-play genetic disease group. This is led by 2 Phase III assets and a bunch of mid-stage programs and a couple of early-stage programs. Nice pipeline behind those lead programs. We've got a couple of interesting genetic dermatology programs. That's, again, led by a Phase III with a pipeline of clinical and preclinical assets behind it. Oncology, again, led by a Phase III and our FGFR inhibitor with some interesting pipeline. And then our gene therapy business unit, which is 3 programs today, 2 of which are entering the clinic this year. And we intend to grow that, yes. Okay. So that's the pipeline. Many of these started actually at Phase -- or at preclinical stages only a couple of years ago. I'm actually just blown away at the way we've been able to advance so many of these in parallel. I think it's really something we've done special here. So now that we've kind of given you a summary of the business and the pipeline, I'd like to dive into a couple of the product stories that we are really focused on right now for various reasons. I'll start with our achondroplasia program. This is one where the scientific story is just really compelling, and we really think we have a chance to come to market with a best-in-class solution for children affected by this condition and their families. So just an overview of the condition. Achondroplasia is one of these not-so-rare rare diseases. It affects more than 50,000 patients in the U.S. and Europe alone, perhaps as many as 100,000 in the accessible global markets. It's one where the genetics are extremely clear. Everyone with achondroplasia has got a gain of function mutation in the FGFR3 receptor. And we know exactly what that mutation does in terms of molecular pathophysiology. It turns on 2 signaling pathways downstream of the receptor that drive the clinical presentation that you see, which is marked by disproportionate short stature, but more importantly, spinal and cranial defects. We're aiming to develop a best-in-class solution here for this condition. We have a potent and selective inhibitor of FGFR1, 2, 3 that we're aiming to administer to children at ultra-low doses, and I'll get to that in a minute. And the reason this is advantageous mechanism, I'll tell you in a second, is we're hitting the disease directly at the source. And so we're shutting down all of the pathogenic signaling downstream of that mutation. On top of that, while we think we can get best-in-class efficacy in this condition, we'll also have potentially the only oral agent available. Solutions today that are in development are daily or perhaps weekly intra -- subcu injections, which we think will be quite burdensome to the children and their families. This is a little bit more of the mechanism slide. So again, we understand precisely what these gain of function mutations do. They cause about a 2- to 3-fold excess of signaling through their FGFR3 receptor relative to wild type. That's quite subtle if you think about kind of kinase mutations that often drive cancer. In those situations, the pathway is often on fire. This is quite a subtle dysregulation. We know exactly what that does. It turns on STAT1 signaling and MAPK signaling. Together, these 2 pathways have unique roles in driving the phenotype in achondroplasia. And that's really important because we think if you want to restore normal growth plate development and correct the phenotype fully, you need to really address both of those pathways. And in fact, there's genetic data where this has been dissected, and we know that they're both important in contributing to the phenotype. So again, we have the ability to hit the disease directly at source, address both of the downstream signaling pathways. And I'll show you some data now on what kind of effect that can translate to in animal models and then how we plan to test this in humans. So what we're looking at here is essentially our compound infigratinib, on the top in red, as tested in the validated mouse model of achondroplasia. So these are not -- this is -- these are kind of cross-trial comparisons here, but these studies were all done in the same model, in the same lab. There's actually one lab in the world that has this model. It's in Paris. So she's done all these studies. So this is kind of as good as it gets in terms of benchmarking across studies. And what you can see here is that on the key metrics of disease features, so long bones, tibia and femur, we tend to do about 3- to 5-fold better than our next nearest competitor, which are the CNP analogs or the FGFR3 ligand trap by Pfizer. And I think the reason for that is we've just got a much more potent and complete inhibitor of the pathogenic signaling that causes the achondroplasia. If you look at the other disease features here, these are probably more important. If you look at foramen magnum area, which is the opening at the base of the skull where the spinal core passes through, or L4-6 (sic) [ L4-L6 ] height, which gets at a spinal disc width, we're showing clear effects on both of these, whereas the other agents that have been put in the clinic and are not really doing anything meaningful. So this is really what gets us and our advisers and the achondroplasia community as excited when we talk to them. Okay. So we are in the clinic. We're in Phase II with this program right now. At the end of the year, last year, we started our observational lead-in portion of the study. The design of our clinical program is to collect baseline growth velocity for 6 months on every kid and then measure growth velocity while on our compound. This is very similar to what's been done in the past by BioMarin. And then find an active dose that's safe and take that into a Phase III registration study. So just one thing to point out here on this page is that you can see the doses in the middle of that chart here, we're testing multiple doses. This is a dose-ranging study. The starting dose is 0.16 milligram per kilogram. Now this molecule was originally developed for cancer, and we're continuing to push it towards the market in cancer. But just to give you a sense of the gap between dose we're talking about here. Our cancer dose is at 125 milligrams daily. If you think about a 30-kilogram kid, the starting dose here is going to be more than 250-fold lower than where we are at in cancer. So we feel pretty good that this will be in a different ballpark in terms of side effect and safety profile. And if you kind of allometrically scale the doses in animals that I showed you on the prior page, these tend to fall within the mid 2 doses or perhaps the fourth dose in this planned study. So we feel pretty good that we'll be able to get to an active dose in a safe way. Looking forward to announcing first trial treated over the next months and plan to share data from this in 2021. The next product story I'd like to touch on is one that's actually going to have first data this year. This is our recombinant collagen VII replacement therapy for a devastating condition called recessive epidermolysis bullosa or RDEB. This is a disease that affects 1,500 to 2,000 people in the U.S. and Europe. It's driven uniformly by loss of function in the collagen VII protein. So collagen VII normally is a structural protein that helps hold your skin and other epithelial layers on to the basement membrane. If you have RDEB, you don't have collagen VII, and so you've got compromised barrier function. Your skin and other epithelia can easily blister. And then once they do blister, they can't heal easily. This causes very painful blisters that you see on this child on the left, but perhaps more importantly, systemic manifestations such as GI distress, lesions in the oral cavity, failure to thrive due to pain and issues, eating and defecating. So really, a devastating systemic disease here. What we're trying to do here is simply replace the missing protein that we've been able to manufacture, recombinant collagen VII, and we're testing it via a simple IV administration in a clinical trial right now. And I think if we can show proof of concept and proof of mechanism in that study, this would really be a best-in-class solution, systemic solution for these kids that I think would be very exciting for the community. Just a quick hit of preclinical data that gives us confidence that this actually could work. It sounds actually a little far-fetched to think that manufacturing an extracellular matrix protein and giving an IV could actually home and integrate into the tissue it needs to. But in fact, in animal models, it seems to be the case. So on the left here, you're looking at tissue sections from the skin and tongue of the mouse model of RDEB, where we gave a single intravenous injection of our recombinant collagen VII. And what those red arrows are pointing to is actually the junction between the dermal and epidermal barrier, so that's exactly where you want the collagen VII to go. And that strong green line staying across the middle is actually immunofluorescence staining of our therapeutic protein. So it indeed looks like it's homing to the tissue where we want it to. You can actually -- and in this paper, there were actually some other types of microscopy done that showed that functional units of the protein are actually forming, anchoring fibrils. So miraculously, it's actually able to get to the skin and other organs and do what it needs to do. This effect is dose-dependent, as you can see in the middle, and a single dose was able to rescue survival in the animal model of RDEB. So we've tested this in one other mouse model and a couple of large animal species, and we've seen the same thing. So we have relatively high confidence that this can do it. Okay. So just a quick word on the trial that we're running right now and the data we plan to share later this year in the second half. So we're running a randomized, placebo-controlled crossover study of our drug BBP-589 over placebo. We've got 4 doses. We're in the third-dose cohort right now. The real thing we're looking to understand in this study, at least in the randomized portion of the study, are: a, can we deliver this protein in a safe way because it's -- I think it's not a given that giving protein replacement therapy will be safe and not cause immune actions. So far, that seems not to be the case as we've been able to escalate through to a third cohort. But the other big proof of concept or proof of mechanism readout we're looking to get here is simply, can we detect our therapeutic protein collagen VII in skin biopsies from these patients as they go through the study. So we're collecting biopsies at screen during the randomization -- the randomized period and then in follow-ups. So what we're looking to show here is that in a dose-dependent, hopefully, way, we can show deposition of our protein in the skin. If we can, I think there's a real reason to believe that this will translate to clinical benefits, which we'll likely be able to observe in the longer-term extension portion of the study. So that's exciting second half readout next year -- this year, sorry. Maybe just running to the last few minutes, maybe I'll just quickly hit a couple other areas of our portfolio that we're very excited about. One is our targeted oncology portfolio. This is, again, a section of this company where we've got some of the, I think, best in the business running the R&D operations. Eli Wallace is running the show. Frank McCormick is also assisting there and helping to find new programs there. He's kind of a legend in the KRAS field and really a founder of the precision oncology movement. And then Richard Scheller, who ran Genentech R&D for many years and contributed to many of their HER2 products. Our strategy is essentially twofold. One, we go after conditions where there's a clear genetic driver, and we can come in with an inhibitor to inhibit the tumor drivers. So this is the case of FGFR or of KRAS. But we're also willing to take a little more target risk in the space for targets that we feel have a lot of scientific validation. So SHP2 is an example of this, GPX4 is another example of this, both targets where we thought we had an edge when we started the program. And those have been progressing well. The next thing I'll hit before turning to upcoming milestones is our gene therapy program. This is, again, a segment of the portfolio where I really think we have a rock-solid team here. We've got folks from -- if you look at the top, kind of the who's who of gene therapy companies that have come to join us. We've built this organization with the help of some of the real academic leaders in the gene therapy space, including Guangping Gao and Pierre Bougnères, Jeff Holt. Our first 2 indications that we've been going into are pretty interesting. The first one, congenital adrenal hyperplasia, is probably one of the largest gene therapy markets that we know of. This affects 75,000 people in the U.S. and Europe likely. And they're all diagnosed, so there won't be a lot of work there in terms of patient identification. This is also one where we anticipate a threshold effect and where we know, based on genetic and functional data, that the threshold you need to achieve in terms of delivery of gene construct into the target organ, adrenal gland, is very low. So we think if we can get to 5% of enzyme activity restore, we might be able to have a profound effect for patients. We've run nonhuman primate studies in that one, plan to submit the IND later this year. Our Canavan disease program, also an IND that's coming later this year. This is probably a smaller end-market opportunity, but one where I think there's a real chance to do something profound for patients. This is a lethal degenerative neuromuscular condition that often meaningfully shortens the life span of children affected. There, we're using an AAV9 capsid to deliver this via IV dosing into the CNS. Again, we've done the nonhuman primate studies, IND being submitted this year. Just announced a new program that's in the discovery stages, the TMC1 therapy for genetic deafness. I think this is just a signal that we're continuing to build in this space. And we've got the people, capabilities and, I think, the appetite to do a lot more in gene therapy. So you should look for us to build here in the coming months, years. Last, but certainly not least, I'd like to hit our TTR stabilizer, AG10 for ATTR cardiomyopathy and polyneuropathy. Just a couple of quick words on this one. This is perhaps one of the biggest upcoming pharma product cycles in ATTR cardiomyopathy. It's a huge condition. There's probably over 400,000 patients in the U.S. and Europe. We're going directly at the disease source with our TTR stabilizer with a best-in-class stabilizer. So we'll come second to market likely, but we think we've got a much superior product to the ones available, say, tafamidis. We recently reported some pretty compelling open-label extension data from our Phase II, which showed a pretty exciting signal on mortality and CV hospitalizations. Looks much lower than what you might expect from looking at natural history or recent precedent studies. And we're, right now, in the midst of executing our Phase III study. We'll have completed enrollment in the second half of this year, release top line data [ second half perhaps ] next year. Just quickly hit the catalyst map. I think this is one of the more packed event calendars that you'll see in biopharma this year, really a year of execution and building. We've got a lot of important studies to get kicked off. A couple of oncology ones, as you see on the left-hand side of the screen, but then in the second half of the year, we'll share that RDEB data I talked about. And also, we'll be starting our achondroplasia study. 2021 is really -- a really packed year of data catalysts, POCs, Phase III readouts. Our TTR study will read out, our Gorlin Syndrome study will read out, we'll have proof of concept, hopefully, in achondroplasia and congenital adrenal hyperplasia. And then we'll also be launching our first 2 products. So really an exciting year for us. This company will be moving from the research and development stage to really a fully integrated pharma company. $577 million in cash as of 4Q. This gets us into 2021. And so yes, excited to execute on these events in the coming months.

Great. Thanks. So we have a breakout session right across the hall. For anybody who wants to follow our conversation. Thanks.