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

Oh, great. Well, thank you so much, everybody. Thank you for joining us Thomas and Julie from BridgeBio. It's really to have you here. And we'll kick it off first with you guys presenting some slides and giving an overly before we start with the Q&A.

Great. Thank you so much for having us, Jeffrey, and thanks to the whole Bernstein team. Tom Trimarchi, President and CFO, BridgeBio, joined by Julie Miller Everett, our Chief Operating Officer of Skills Blasio's business. Many of you will know Julie from her critical role in the Attribute launch, and we've just moved over to help with the infragratinib launch where she brings more than a decade of commercial experience, particularly in the ultra-rare and skeletal display space. So I'm really privileged to have her with me here today. Maybe I'll start just by saying a few words and setting some context for hopefully a great dialogue here with today, Jeffrey. So BridgeBio is a company that at the highest level, we're here in this world to help as many patients living with genetic disease as we possibly can in the shortest amount of time that we can get that done. And we do that through creating first or best-in-class medicines and putting them out into the marketplace. Today, the business late-stage portfolio is incredibly unique if you've studied the industry, you're certainly looking at it today as I know you are. So first, we've got Attruby, which is our best-in-class near-complete stabilizer for ATTR cardiomyopathy. We're about 6 quarters into that launch. That the importance of that loss to our business cannot be overstated. So at once, I think that has proven us as a capable commercial organization, and I think that is widely regarded as 1 of the better biotech launches we've seen in recent years annualizing north of $1 billion today globally on track to be on a full year basis, blockbuster status globally by the end of this year. Really, that's added to a few things. First, -- this is a large and expanding marketplace. We're seeing something like 15,000, 16,000 patients come to bolt in the funnel every year. So really really attractive from a patient need standpoint. And I think we have clearly a differentiated and best-in-class stabilizer, which are post some of the recent data sets, I would say, solidified as the backbone of first-line therapy. So really exciting molecule there. And actually, this morning, we had some incredibly important news come out we published the first of its kind real-world data set comparing Attruby directly to tafamidis, where we've seen about 1/3 improvement in the composite of -- including all-cost modality and CV hospitalization. So a really important data set that has not really yet been disseminated to the marketplace and impact the prescribing behaviors, but that will take place in the coming year. So really proves us out as a competent commercial organization and also, I think, gives us the confidence to launch the next 3 products, not only in the U.S. but globally. So I think the really unique thing about BridgeBio today is that still early days of product launch and another 3 coming in the next year. So we've got LimbGirdle which is first-in-class molecule for a high unmet need for muscular dystrophy. There we've got a product that can actually remarkably improve function on several on patients are able to breathe better than when they started therapy. They're able to walk better and they're able to actually through a measure of general symptom scores like the North Star restore overall function and statistically significant way against placebo. So really, really exciting molecule that that's going to do a lot of good for patients. This is a clear billion opportunity ADH1 in Caleres another small molecule that's read out Phase III in the next -- in the last year or so, again, basically functionally cured about 76% of the patients in our Phase III. So really improved data set that's going to change a lot of lives in this marketplace. And there, again, we've got $1 billion opportunity, no competition looking forward to building that market. Finally, achondroplasia, which I hope we have plenty of time to speak about given we've got Julie with us. This is today a $1 billion marketplace where we're going to come in with a quick distinct, differentiated and unique molecule only oral in the space and a pivotal data set that really is giving the market exactly what it's been asking for, for many years, which is really a profound effect on height, but more importantly, compelling effect on the health of these children, whether it's proportionality or some of the things we've been able to demonstrate recently, including an effect on sleep apnea and our infection. So overall, the picture Attruby we see is on track to deliver $1 billion-plus in peak year sales. And then we've got another $4 billion, I would say, derisked and about to see uptake into the marketplace next year. with expansion available to us beyond that, there's some interesting opportunities, including hypochondroplasia and other skills as well as surgical hypoparathyro -- that's the opportunity in the next 8 months, I would say. Beyond that, our hope is that we can create many, many meaningful medicines for patients on the floor that I talked about -- and have a durable business that can grow for many days. And so beyond the 4 products that hopefully we'll spend most of time on today, we've got had -- we've had a very prolific productive discovery engine that's continuing to put molecules in the clinic. So I think when the time is right, we can access some of that pipeline growth. It's house today in our sister company called GolaBiowhich is private. So with that long-winded perhaps content setting, maybe we can get right into the Q&A.

It was a great setting. And yes, we'll definitely touch on a lot of these drugs doing our conversation in more. So maybe even maybe taking just a step back, just as an introduction, I love to hear what both of you think is sort of the DNA of the company, what makes Bridge Biotech and why are you so successful?

Thank you for saying that. I would say 2 things in my mind are different and special about this company. First, -- and this comes back to the patient impact mission. We really try and work on diseases where there's both a tremendous unmet need out in the community, either there's no available therapy today or existing therapies are inadequate. And we tried to work on diseases where we can ask how do we drive a large magnitude of impact for patients. And for us, that usually brings us to conditions where we can take a complicated biological problem and convert it to something much more like an engineering issue where we can kind of connect all the dots between genetics and what we need to do to the target and how we affect it to translate to symptoms and outcomes for patients. And when you do that, I think you can, a, drive probability of technical success even beyond the all-comer kind of generic disease levels. And I think we've demonstrated for the first 10 years that we can do that. And be it lets you really have a clear thesis on what your therapy hypothesis is a it's not working and it's no longer intact, you can kill it and reallocate resources elsewhere. So that's, I think, one thing in terms of the operating system that is unique and it's allowed us to be successful. Two, from a business standpoint, I think we catch a little bit of flack from time to time for investors who're spending too much talking about NPV, but it actually does matter if you want to -- to create a business that is going to be durable for generations to come. You really have to be focused on am I investing in a way that's going to allow me to be sustainable from an economic standpoint. And I think clearly, if you look at kind of like the opportunity for us to transition our P&L over the next 18 months, I think that clearly has benefited us today. So those are 2 things that pop into top of my mind, but Julie.

Yes. Well said. I would just add one more, which is that we have truly differentiated clinical science and outcomes. And when you look at kind of the 2 pillars that we're building as an organization right now for commercial execution. We have hypercompetitive markets like amyloidosis and achondroplasia, where we have best-in-class products that are truly differentiated if you follow the science and the literature. And then we have Pillar 2, which is these traditional rare disease markets where we're building a market based on clinically defined conditions, well-articulated science, high unmet need. So I think that's really what differentiates us is having a scientific but also commercial organization that's able to develop drugs and then execute across both pillars.

That's excellent. And maybe kicking it off, as you've given a really nice overview that highlighted some current key drugs in the near term and on market now. I'd love to maybe just start with the Atruby give us overview any additional information you want to share beyond your nice introduction upfront and how important it is for patients and for the company.

Yes, absolutely. So true, as I mentioned, that's annualizing today north of $1 billion just 6 quarters into launch. And it's a really interesting moment for this product where we see a large and continuously expanding market as I mentioned, 15,000, 16,000 new patients a year right now today is our estimate. Just 2 years ago, that was more like 8,000 last year something like 10,000 to 12,000 was our estimate. So we continue to see strong momentum for the market overall. And at the same time, we continue to grow our share of the market. And I think we're really entering, I would say, kind of a second chapter of the tribe launched. First 6 quarters. We're really about getting out there, getting into the centers of excellence, establishing ourselves as the new player, the differentiated player and really grabbing market share with our initial marketing message that were really anchored around the primary analysis from our Phase III study, so 3450 3-month separation, 42% reduction in hospitalizations and mortality and a 50% reduction in hospitalizations, which, by the way, giving a shifting patient population, most events that occur in this population of state in hospitalization. So really important that we have strong data there. So I think that has gotten us where we are today, which is about 25% share of new patient starts and growing. And really the next leg up of growth is going to come from a bunch of new data sets that we've just put out into the market or have been shared with the marketplace through competitive updates. So on our end, we've seen 2 really important new pieces of data come out very recently. First, we've published an effect that shows a Atruby actually can have a kidney protective effect in these patients, right? And actually a animates something we're still working on, and I think we're going to have dedicated studies to actually demonstrate this in a prospective way. But I think that could explain why we see separation on outcomes as early as one month or within weeks of treatment. That's really important. I think that is just starting to be disseminated into the marketplace, and we could see an effect on prescribed behaviors there in the year to come. Second, as I mentioned this morning, real-world data set. I mean, one of the big questions we've had from prescribers that are more on the fence in terms of preference for Atruby versus anything else that's been okay, I can see scientifically that you've got a much more potent molecule. But it's very difficult for me to compare across clinical studies. They were running different eras. The population has been shifting rapidly. How do I really know that it's going to deliver a differential outcome for patients? And actually, sometimes they ask the patient which met they want to be able is -- not great, if you ask me. But -- so I think the real-world data set we've published this morning is going to be very impactful in answering that question of does more stabilization truly matter in terms of outcomes. And so again, what we've seen there is a 34% improvement on the composite of diuretic intensification, CV hospitalizations and all-cause mortality for Atruvis compared to tafamidis. And again, that effect is seen in weeks, not months or years or so, hopefully, we can create some urgency to start using ETRUVIan new patients or even switch more of your TAF patients on to TRU -- and there's going to be more to come, right? I think there is -- when you see a study coming from sponsor, there's sometimes appropriate skepticism as to the methodology there, but there's an independent real-world data set coming out in what is it, 2 weeks or 3 weeks at HFSA, which hopefully can provide additional validation of what we've published this morning in our study. So I see Chapter 2 of this launch being driven by some of these newer sets and leading to really a reacceleration of growth as we look into second half of next year.

That's great. And more data, especially rural world data sets are very helpful. And it's great to see. Talk speaking of recent data a bit of a different mechanism, but cardio transform was presided ESC last month. Just curious what you think of that data set and how it could be impacting the stabilizer class I realize it's a silencer, but it was a very impacted presentation last month at ESC.

Yes. And Julie, feel free to chime in here. But I think the little feedback here, sorry. I think the most important takeaway from that data set was this whole concept of combining a stabilizer and a knockdown -- is really without any merit. I mean we've seen no treatment effect of adding a knock down on top of even a weak stabilizer. And so for the prescribers that we're thinking that might be a good idea scientifically and could lead to a good outcome for patients. I think we have just too much evidence today to continue with that. And you saw from multiple major KOLs in the podium say, this is practice-changing, meaning that is no longer an approach that we should be thinking about for patients. And that really suggests that frontline backbone of standard of care ought to be a stabilizer. And I think as we just discussed, all of the data sets coming out here continue to suggest that TruBoought to be your treatment of choice and where you start. It's going to take some time. It's going to take some effort. It won't happen -- I had a lot of fighting and repetition and educating the marketplace, but we're optimistic for the data toll on our side, and we can continue growing share over the next year and beyond.

I think -- yes, well, the only thing I would add to that is I think 1 of the other things that clarified is this concept of like how do you define efficacy in cardiac amyloidosis. And Mechanistically speaking, we discuss a lot this concept of the TTR tetramer. And ultimately, what's disease causing is the toxic monomer and when cardio transform read out, a lot of folks started digging into what is what we call like mean max efficacy. And when you look at the stabilizers, you have tafamidis, it's about a 60% stabilizer meaning 40% monomer still forming disease. You have agramedus that's greater than 90% stabilizer. So less than 10% toxic monomer disease forming. And then when you look at the knockdowns, it's the inverse, right? It's like how much do you knock down and then toxic monomer remaining. And we saw that with with eplonteresen as well as Amvutra, they were in the 60s to 80s, right? So scientifically speaking, I think a lot of dots were connected on an outcomes basis that prior to cardio transform were more of a theoretical basis. So it's nice for us now to see narrative evolved -- and final point is that even with tafamidis, more is that background therapy in cardio transform and still seeing no benefit. Now doctors are also to Tom's point, taking into account what we've seen with the stabilization data Aqaamedus being a more complete stabilizer. You now see the real-world evidence, you see the kidney protection data, and it just takes it to the next level that even with tafamidis, the trial was not successful with acoramadis as the backbone of care. I think it's even further differentiated from the knockdowns.

I would just say 2 more things that kind of struck me.

We like this topic.

Really important from E&C. One, you've continued to see event rates go down with the shifting population better care. That's really important because I think we can say almost definitively now a head-to-head study, it's not possible. So that let's increase importance on real-world data sets like we just reported this morning in terms of providing evidence for treatment decisions. Two, Really, I think related -- it means that most of the events happening today are hospitalizations. And so it makes it that much more important to have really, really compelling hospitalization data in your -- around your molecule, and we have market-leading data there. as well. So 50% reduction in hospitalization in just 30 months. So I think we are positioned extremely well to continue growing this brand over the next years to come. It's not going to happen overnight -- but with, I think, the right team, the right resourcing and a little bit of luck, I think this can be a massive product for us and impact for patients.

Absolutely. Well, just asking a sales question, what -- how do you -- how should we be thinking about the quarter quarter-by-quarter dynamics for Atruby sales.

Yes. So I think for the next several quarters, I'd say, until we get into really end of 2027, we'd be thinking about kind of a $25 million to $30 million quarter-on-quarter, absolute delta. And that's driven by a few things, really. First would be a dynamic around second line, the tafamidis switch. So we saw a pretty significant kind of bolus pool of patients early in our launch that we're coming off of tafamidis onto new products, ours and Bogota knockdown, which makes sense, right? This is a market where there was 1 player in town for a long time. That was tafamidis was a huge step up in terms of care for patients, but clearly inadequate, right, in terms of level of efficacy and stabilization. So we knew there was a big pool of patients that were progressing and worsening but had nothing to switch to. So I've just been hanging on to them. So we saw early in our launch, I would say, a larger-than-expected contribution from tafamidis switchers, certainly, what we can ascertain from dynamics around the knockdowns as they were benefiting significantly from switch early on in the launch too. And I think at this point, we've kind of worked through that initial pool, and that's normalized. So second line is growing. And I would say, steady state now, which is lower than it was a year ago. And so that's one thing that's, I think, influencing kind of like the near-term quarter-on-quarter dynamics. 2 is related, which is duration related to patient mix. So as I said, early in the launch, contribution from second line was bigger than we would have expected -- and that has shifted towards a greater and greater frontline contribution over the -- every quarter since launch to the point where today, new starts volume is vast majority is treatment in frontline share. But we're dealing with duration from the cohort that came out drug 6 quarters ago. So. So that's another thing that I think you should be mindful of as you think about quarter-on-quarter dynamics near term. Then I think come late 2027, all of these new data sets that we've been talking about should begin to get reflected in treatment behavior and share, and we'll start to see a reacceleration of sales growth at that point.

That's great. In terms -- you sort of highlighted the Attruby launch, great data that's just being released just now, your real-world studies. And now maybe looking even beyond that life cycle management. Is there anything you would like to highlight or thinking through when you want to speak to what the potential life cycle management of the drug could be?

I'll start. Julie chime in. I mean, I think there's at least Three important studies that we're thinking about right now. One is the actuorily study, which is the first of its kind. This is a primary prevention study in variant patients where based on high risk of progression from being asymptomatic to having heart failure based on family history and various other factors. You were randomizing patients to placebo or Attruby. And the goal there would be to prevent patients from progressing to heart failure. This is analogous to what we've seen in the statin class with some of those seminal studies there. Practice changing, basically, disease prevention is always kind of the goal, if you can figure out a way to do it. So that's key. And I think that also has the effect today of helping drive the narrative around early diagnosis, early intervention even for patients that do show up to the clinic with heart failure, don't wait, right, actually. Two, we've just kicked off a cardiac imaging study. The goal there is going to be to show basically to elaborate on a signal that we saw in our Phase III study in the substudy that we had with cardiac imaging. We want to see actual cardiac MRI-based disease reversal. We think it's possible based on the signal we've seen and based on the potency of Attruby. But I think if we can show that in a prospective study, dedicated study that again, would have the opportunity to be practice-changing. And third, as we talked about, we're looking for ways to elaborate on and again, validate this renal protective effect that we've seen from our Phase III in a dedicated prospect study. That really just allows physicians to understand this effect and understand that it is distinct and unique from other approaches that are out there today and really can explain some of the compelling data we've seen on the early separation of albums, whether compared to placebo or again in a real-world setting, compared to fames where you see separation within weeks.

Well, before moving on to the next -- any last comments on Attruby we feel like we haven't had a chance to discuss yet. Anything else?