BridgeBio Pharma, Inc. ($BBIO)

Hi, everyone. Good afternoon. I'm Ellie Merle, one of the biotech analysts here at Barclays. Very excited to have Neil Kumar here with us joining from BridgeBio, CEO. Thank you so much, Neil, for making the time.

Thanks for having me. Really appreciate it.

A lot to talk about across your 4 late-stage programs. Maybe just because it's topical now, let's talk about what we learned yesterday from the tafamidis IP Phase?

Sure. Let's get right into it. So just as a reminder, this is an IP situation that is related to a competitor's drug product. So I'll stay relatively high level in and around it. But effectively, there are 2 key battlegrounds that I think people are paying attention to in the context of this trial and the defense that Pfizer is conducting of its Vyndamax patent estate that should take it out to 2035. The first has to do with infringement and the second has to do with validity. And really, what we learned about yesterday probably focuses more on infringement where we think the case is relatively clear, but I know that, that's been a key point of controversy throughout the course of the last couple of months. And there, if you just sort of think about Gibbs free energy in different crystalline forms, you have the low-free energy form, the low-free energy polymorph that is protected. It is the claim that Pfizer has asserted against all of the generic manufacturers in the context of this trial. And the interesting thing that they've done very cleverly is -- or very astutely, I should say, scientifically is to use 3 orthogonal methods to effectively define what that low-free energy form is, obviously, solid-state NMR, XRD, those 2 technologies tend to do the heavy lifting typically on free energy form polymorphs. But then the third one is Raman spectroscopy. And what we learned yesterday was one of the key experts associated with spectroscopy and I think just broadly will be allowed to testify, which I think is an important piece of what we're going to see. I also think it's reasonably apparent at least to us that Pfizer must have found this low-free energy form and most of the material that they have surveilled. Otherwise, they would not be applying the claim against these generic manufacturers. And obviously, Dexcel has already said that they are infringing. So we believe that infringement piece for a wide variety of reasons, mostly scientific, is strong. But I think having the strength of Adam as an expert there will be critical as well. And obviously, their experts across both validity and infringement, I think, are a strong cast. They do have RA as well and [ Burnie Trout ] testifying in and around validity. So it should be a strong cast that we think will be congruent with their strong case.

And investor question we get is there's so much focus on Vyndamax, but a Vyndaqel generic, we could see end of 2028. Why does this not matter?

Well, everything matters. I would say the Vyndagel generic, Vyndagel as a brand has been discontinued, as you know, from the marketplace. It doesn't mean it can't be relaunched in some way, shape or form. It's also not substitutable. Obviously, there's different levels of API, and it's not what they're running current experiments with to continue to elaborate on the health benefits of this franchise. It's sort of like are payers really controlling this category that astutely. I mean, in Europe, like Attruby is the leading brand, we're effectively generic as compared to Alnylam, and you don't see a whole lot of payer control. And I think when you think about the economics in the channel, given the fact that patient co-pays are all going to be the same because this is mostly a [ Medi D ] population, that the ISPs generally are going to want branded products and that brands are going to continue to do the research in this space. And there's a lot of research to be done. You put all those together, I don't think Vyndaqel itself will be a competitive brand, maybe outside the VA or VA often will use 20 mg TAF. And then there are some institutions that use diflunisal as well as a generic that's generically a better stabilizer than 20 mg TAF. So there will be, I think, small pockets of usage, but it's -- I think Vyndamax is the big brand to pay attention to.

Okay. That's helpful. I'll probably have more questions if we have time on that. But I do want to focus on your portfolio outside of achondroplasia and ATTR since I think that gets so much airtime, I mean, as it deserves. But I think the pipeline beyond that is very valuable as well, and I think it's worth talking about. Maybe starting with ADH1, how should we think about the size of this opportunity and what drives your conviction here?

Yes. Well, I guess, first and foremost, what drives my conviction is this is a big unmet need with no therapies available today and the Phase III data were markedly compelling. I mean when you're talking about 75-plus percent normalization for patients, I mean, really, that's almost like a therapeutic cure, as I've said, 91% of people getting their PTH back into the normal realm as well. So that type of thing is super exciting for the patient population. And then the question is, how do we find and activate that patient population. And so the second thing that excites me is this is a broadly prevalent disease from the statistical genetic standpoint, 10,000 to 12,000 people. It's not a pediatric condition that necessarily limits lifespan. So you can imagine that the population is large, but I would say a majority is unfound, not only TTR, and certainly not unlike TTR prior to the move from cardiac biopsy to technetium scan. And so how do we find it in this case? The good news is there's a subpopulation, nonsurgical hypopara where we can look. And pretty reliably, we're finding something like 20% to 25% of patients have hyperactivated mutations in the calcium-sensing receptor, which is what qualifies you -- what defines you effectively as an ADH1 patient. So I think there's a reasonably large unmet need. I think this drug is really a beautiful product for those patients. And I think there's probably 3,000 to 4,000 already identified patients that we could launch into now. And it's a safe oral that has outstanding efficacy. So that's what gets us excited about that.

Should we expect a bolus for the launch?

I think -- I mean, there's a bolus on every launch, except for when you give drug away for free, I suppose. But yes, generally, there's going to be a bolus, I think, associated with the pent-up demand in this space. Yes. I mean that's kind of what was cool about -- I mean just generally, if you like model these launches, we have this revenue institute thing and it's like in rare disease, you typically see this -- there's basically a steep incline. And then there's a flattening in terms of the actual growth. And then when the second derivative gets positive again, like you see in TTR, that's super exciting because it means there's new prescribers or there's a new dynamic available. I think it's for TTR, it's, by the way, just new prescribers and high-volume heart failure practices. So I imagine it will be a little bit like that here, too, in ADH1, like I think you'll see a relatively steep incline. And then you'll see a flattening in terms of growth. And then as we find new patients and find new prescribers outside of the severe endocrine population, and then we'll see more growth there.

What proportion of these patients are currently on [ Urispas ]?

Like 1%, I don't know if you...

Really.

Yes, it's not labeled for it. It's -- I mean there was that New England Journal piece, but we don't see a lot of patients on it, seeing many more patients actually on standard of care, which is ineffective and obviously exacerbates the urine figure and calcium, but I don't see a lot of patients on URV right now.

Okay. Let's talk about limb-girdle 2I, maybe the population there and how you see the opportunity?

Yes. So super exciting. I actually just flew up this morning from Orlando, where MDA is ongoing. And I think that, that data is going to be -- we have a late breaker that we got a press release coming out in an hour on some of the new data associated with it, but very privileged to have Dr. Kathy Matthews presenting our data in one of the keynotes there. So again, I think my excitement in that space starts with the outstanding data that definitely surprised me to the upside in terms of the interim Phase III readout. Not only are we having really, really significant action on the causal biomarker of the condition, which is glycosylation of the alpha-dystroglycan complex, like 80% increases and in some cases, taking people back to normal levels of glycosylation. We're also having that impact on CK where you'll see that a reasonable fraction of patients are actually back to normal CK levels, which is, as people know, a very sensitive measure of muscle damage. But most importantly, those functional improvements. And like to me, it's truly remarkable when you see a therapy that's not like slowing the condition, but actually improving it and it improves it on ambulation, all measures of ambulation as I think people will see from the keynote address plus FVC plus modified North Star test and you have that early action as early as 3 months. So I think all of those things put together, it's like this is a really, really devastating condition, again, no available pharmaceutical therapies and probably something like 1,200 to 1,500 patients in the United States. This was a little better identified at the get-go. Actually, there's -- if you look at Iowa, you look at VCU, you look at some of these larger institutions, they have quite a few patients. And there's 150, I think, MDA centers of excellence across America. And I think they all have reasonable numbers of LGMD2I patients or at least LGMD patients. And then the question is you just have to genotype them. Prior to probably not a huge deal to not genotype them because there weren't a lot of available pharmaceutical therapies, but now I think people will be doing that more.

Makes sense. And how should we think about the pathway to approval and the use of the sort of surrogate or biomarker?

Yes. I think given the fact that we had the statistically significant impacts on outcomes and inclusive of modest [indiscernible] North Star, our dialogue with the agency -- I should also say, one of the things the agency always looks at is what is the consistency of the data. You don't want a few outliers driving the signal. And here, it's been remarkably consistent, not only in terms of patient to patient, but also the subpopulations. If you look at the compound H versus the L276i homozygous patient population, if you look old versus young, if you look at severely affected in terms of FVC, nonseverely infected, it's a very constant sort of gorgeous forest plot. We've shown some of that publicly, and I think the rest of it will be shown this afternoon. So I think given all of that, the agency's dialogue with us has been oriented toward full approval. And that's how we would expect to proceed.

That's exciting. And what about your conversations with ex-U.S. regulators?

Yes. So in Europe, we haven't had as detailed discussions yet, but we anticipate having those in about 2 months, where I think I'll have a better understanding of how they're thinking about the data set. But I don't imagine it would be highly discrepant to what has happened thus far. The data is the same data.

It's exciting. And this time next year, you could be launching 2 or 3 more drugs.

Yes. Super exciting.

How are you thinking about the commercial build-out, particularly ex-U.S. and what that might entail?

Yes, great question. I mean I would say, by and large, the commercial build starts with the decentralized model that we employ here in the U.S. So every affiliate is really going to be almost like if you think about big pharma, the global product leader or whatever, like, yes, every affiliate really owns the science, they own the medical affairs, et cetera. But then they get to hook up to the centralized commercial infrastructure that we have, at least in the United States, which does patient services, market access and distribution and design and sales force incentives and training and all of that stuff. So I think it's -- they're going to be highly efficient launches from that standpoint. And we're never going to have to build the type of field force that we had to build for TTR for any of these, even including in achon. So I think that should be fairly efficient. Ex-U.S., I mean, this will be the first time we're launching, obviously, since we're partnered with Bayer in Europe. And so we've got Hassan Jaroudi, who's done a lot of this work at Alexion, and we're excited for the opportunity to serve patients in Europe. Obviously, the one big advantage in Europe is that there's small numbers of centers of excellence that account for many more of these patients. And you can see some of these launch dynamics even in the achondroplasia ex U.S. launch versus the U.S. launch, it's easy to understand and find where those patients are. But I'm not negating the complexity of what we need to do, but that's one advantage. The second advantage is for every single one of these trials that we run, they have been global trials. So just like with TTR actually, and I think you can see this from Attruby's leadership in Europe, in part, it's been a great job from Bayer. In part, that's been obviously the more marked focus on just looking at point estimates at 30 months and price points. But I think it's also been true that the goodwill you build up when you run these international trials, and we've run almost 30%, 35% of our population comes from Europe in all of these clinical trials, people have experience with these products and what they can do for their patients so.

Makes sense. Turning to Attruby. So we saw an acceleration in new patient starts in 4Q. What was the driver of this? And what should we expect throughout 2026?

Yes. I think, by and large, a big driver has been -- because you saw the uptick not only in scripts, but you also saw it in terms of number of prescribing physicians. So -- and this is not just us. I think this is all sponsors have been doing a great job of getting out to these high-volume heart failure practices and really educating on how you might find these patients. I've probably not given enough credit to what these EMR flags and "AI algorithms" and things of that nature could do to help just physicians think about, "hey, this might be an ATTR cardiomyopathy patient. " So I think that's one thing that's really helped. I think the second thing is the applicability, especially of small molecule stabilizers in those practices has helped us quite a bit. I mean I don't think Wall Street maybe gave as much attention to some of the subpopulation work that we had done over the course of the last year. But like the cardiac arrhythmic data was really, really interesting, I think, to physicians, especially in that "community" or JV setting because not only did it show impact on AF and obviously, hospitalization in the context of the cardiac arrhythmic population, which is like the majority of the patients, 50% to 60% of these patients have some sort of Afib involvement. But most importantly, what it showed is the drug is active in non-Afib and Afib patients similarly. So you don't really have to worry about because Afib can be a complicated thing to manage. And so the simpler you can make the therapeutic choice and actually the way you manage patients, the better off physicians and patients are. And so I think a lot of that work that we've done has excited people and gotten us off to the right start in terms of naive share in that setting. So I'd say that's the second big driver of what we're seeing is just the continued prosecution of the data.

What are you seeing in terms of the types of prescribers or the types of centers where you're gaining the most share?

Yes. To be honest, I mean, we've heartenedly been able to gain across the board. I would say like we started at a slight disadvantage in the academic medical centers because they had experience with some of these other things through polyneuropathy. And then obviously, the knockdown economics are a little bit different in academic medical centers where they might focus more. But again, I think for our prescriber base, it really comes down to the efficacy. And I think there's 2 stories that have really been, I think, winning the day there. One is the serum TTR story, where it's pretty clear that ever better levels of stabilization now. Pfizer did a solid in publishing their 2 papers on that as well, lead to ever better decreases in risk of mortality at 30 months. So I think that's been one thing. And then the second thing, I think, is the early separation. Maybe haven't caught as much on in the community setting, but I think in community, I mean, the non-AMC setting. non-COE setting. But I think people are really paying attention to that, especially given some of the mechanistic work that we've been doing in collaboration with them on how is that occurring? How is that separation in morbidity occurring as early as 1 month. It's probably not the kinetics of monomeric deposition in the heart. It could be something else, and we believe it has to do with the cardiorenal access, which we continue to explore. So that will be the second thing. And so like AMC, I see us picking up there. And then certainly, in these high-volume heart failure doctor practices, I think we've done a good job of educating on the benefits of a superior stabilizer. And it generally has been paying off for us in that setting as well. So I'd say in both settings, we've been picking up neither brand or naive share.

Anything that you would call out specifically around any 1Q dynamics you expect?

Not really. No, I can't think of anything interesting to say on that front.

That's encouraging. In terms of thinking about the price evolution long term, and I think that's really where a lot of the generic tafamidis conversation comes from. How are you thinking about this even say, over the course of 2026 with the evolution of gross net, but then, of course, longer term, when we see potential generics regardless of what year that may be?

Yes, it's a good question. I mean, obviously, the price has been going nothing, but up in the channel right now in part because of the -- that's only true in the U.S., and that's true because of the dynamics of the channel. And like I said, I mean, we're effectively -- I mean, we're the lowest priced drug in the marketplace, and I wouldn't say that necessarily helps us with some of the middle intermediaries. Ultimately, I believe it helps us with physicians and patients. But what helps us more is the hypergenous access programs that we have. It's not -- this is not an easy category to manage, and that's why I don't think you're seeing it being managed in the United States all that effectively, mostly because there's not an obvious physical marker of nonresponse. And so like how are you going to like necessarily step one thing versus another. It really comes down to it's a devastating deleterious disease and a physician is going to feel like one product is better than another to put their patient on and they often will. I mean I think there are some people who are very cost sensitive and might be using diflunisal, as I mentioned earlier, a 20 mg TAF. I don't think that's a very good thing for patients, to be honest. I mean I do think -- I don't know how many more times and how many more experiments need to be put out there to show that ever better levels of stabilization lead to better outcomes for patients. But I can't -- it's never going to be 100% answer there. But long story short, I don't see price dramatically changing in this category in the near term.

Okay. That's helpful context. Some exciting data from infigratinib in achondroplasia. As we head into the hypochondroplasia Phase II data in the second half, which I think was an interesting readout. What are you looking to see? And what are your expectations for what we'll get from an efficacy perspective in hypochon relative to achon?

Yes. So I think achon again, was -- I mean, I expected that trial to be materially positive, but I think that the 2.1, the third standard deviation for the Z score and certainly, the proportionality with the p-value probably slightly exceeded my expectations. So there again, that makes me excited about what's coming with hypochon. Hypocon is a less well-described condition. Obviously, we don't have like the totality of the growth curves and all that, like we have the Hoover-Fong curves, et cetera, in achondroplasia. But I think in hypochon, first and foremost, we want to show some statistically significant impact on change from baseline in AHV. And I think really just get into the setting of hypochon, I think people will already given the mechanism and given the results in achondroplasia, I think people will be quite excited about that type of product.

And how are you thinking about the commercial opportunity in hypochon relative to achon?

I think -- actually, it's interesting. Someone was asking me about that earlier today, and I was thinking about it, like the enrollment rate for hypochon has been very high, which at first, I thought hypochon was a little less well diagnosed and could -- it probably is, to be honest. But the enrollment rate has been terrifically fast actually in our Phase II. So I would say the statistical genetic prevalence is pretty similar between hypochon and achon. I don't think there's as many identified [ ketos ] right now in the space, but I think it could be very rapid because, again, these conditions are fairly obviously diagnosed. It's not necessarily a hidden condition like even an ADH1 might be.

As you think about the size, I mean, you have a large pipeline of these various indications between ADH1, limb-girdle, achondroplasia, hypochondroplasia, how would you order them in terms of when you do your internal modeling around peak sales?

Well, TTR is definitely the biggest. We think that's a $4 billion peak year product. And I think that's fairly consistent with the data that is being generated right now, commercial data, I mean. I'd say on the achon side, we believe probably $2 billion, and that's not including hypochon. So we haven't quite modeled -- we have to hit on our Phase II first to start including that in our PK models. And I think for both ADH1 and LGMD2I, we have them at $1 billion peak. And I think some of what people are missing is the ability to price appropriately for the type of data that we have put forth in those 2 indications. So I think those are 2 meaningful marketplaces for us that are probably getting a bit of short shift. So that's how I would order them. Obviously, the big thing that can move that is we're kicking off a Phase III in chronic hyperpara this year, this summer. And that's a monster market, and that could materially change the marketplace for encaleret. But again, we haven't hit on that yet. So that would be my ordering for the stuff that is post Phase III.

Okay. Great. That's helpful. And then taking a step back, I mean, you have a very unique business model and how you source assets and have a diversified portfolio. Beyond the programs that we talked about, can you speak a bit to your business strategy as well as some of the other earlier programs?

Yes, I would be delighted to. Obviously, right now, we're in the midst of a fairly heavy execution phase. We want to make sure that we get great labels and launch these drug products for the patients that we serve. And then secondly, elaborate on all the opportunity associated with the existing medicines. Hypochon, we talked about, chronic hyperpara, I just touched on. There's some smaller skeletal dysplasias and other growth and other height-associated disorders that we might look at as well with infigratinib. And then we have a fifth program in Canavan disease, which I don't think will be super material commercially, but it's very, very important to the patient community that we serve. Beyond that, we have obviously -- well, maybe not obviously, but we have a -- this is maybe one of the most exciting and also noncompetitive times in genetic medicine that I'd say it kind of reminds me of like when we started BridgeBio, there's so much substrate and no one cares because everyone is doing like obesity and I&I. So we've been able to accrue a very exciting pipeline at Gondola, which is kind of our off-balance sheet partner for doing R&D. And we talked publicly about one of those compounds, which we believe is a best-in-class potential EPP product that has finished its Phase II, several more ideas like that across ADPKD and alpha-1 antitrypsin deficiency and TSC and I think with the potential for 8 development candidates in the next 6 months there. And I think broadly, like outside of what we might do with our sister organization there, we're more focused on organic versus inorganic growth. Inorganic growth is very expensive. and the fact that we're getting to INDs and $15 million or less and all of these Phase IIs that we just talked about today, we're like $220 million or less all the way from front to back. So I feel like we can do that work for the patients that we serve pretty efficiently, and we have a lot of ideas. So our hope is that we're able to kind of correct -- capture the intrinsic value that we've generated for the investors that we're serving here and then turn around and do more of it.

Great. Well, I know we're out of time. But Neil, thank you so much for joining us, and appreciate all your insights.

Yes. Thank you. Appreciate you having me here.

Thank you.