BBIO - NASDAQ

Good afternoon. I will be your conference operator today. [Operator Instructions] Before we begin, I would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities laws, including, but not limited to, statements about BridgeBio's future operating and financial performance, business plans and prospects and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward-looking statements. For a discussion of these risks and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. With that completed, BridgeBio, you may begin your conference.

Good afternoon, everyone, and thank you for joining BridgeBio Pharma's Third Quarter 2025 Earnings Call. I'm Chinmay Shukla, Senior Vice President of Strategic Finance at BridgeBio. With me today are Neil Kumar, our CEO, who will provide opening remarks and discuss overall corporate performance; Matt Outten, our Chief Commercial Officer, who will provide more details about our commercial performance, particularly the continued success of Attruby; and Tom Trimarchi, our President and CFO, who will review our financial results. During today's call, we'll cover our strong commercial execution in Attruby's third quarter on the market. We'll provide updates on our late-stage pipeline, including the Phase III readouts of encaleret and BBP-418, which were announced this week, as well as discuss infigratinib in achondroplasia, which we expect to read out in early '26. We will end with a discussion of our robust financial position. Following our prepared remarks, we will open the call for Q&A. For the question-and-answer session, we will also be joined by Ananth Sridhar, Anna Wade and Justin To, who lead encaleret, BBP-418 and infigratinib, respectively. With that, I'll turn it over to Neil for his remarks.

Thank you, everyone, for joining us today. As always, this is a forum in which we communicate salient aspects of our business that are of interest to investors, and we welcome your questions and feedback along the way. On the first 2 of these calls we have done, I've focused my early comments on Attruby, which continues to be the core of our business. As both Matt and I will elaborate on, we see continued momentum, both scientifically and commercially in this franchise and are ever more confident today that we will achieve our goal of 30-plus percent market share by volume in the years to come. But I wanted to start today by talking about our recent R&D progress. As you all know, we had the distinct privilege of announcing 2 stellar Phase III top line results over the last 3 days. It is quite the coincidence that these readouts happen to stack on top of one another after 6-plus years of working on these programs. But these few days serve as a testament to the longer-term productivity of the R&D engine we have created. Slide 10 of our updated corporate presentation shows the industry-leading time lines that we have been able to achieve, and Slide 11 shows the remarkably high probability of technical success across our programs across the nearly 10 years that we've been operating. Probabilities of technical success north of 70% start to move us from a lottery ticket-like entity to an engineering company-like entity, one that will undoubtedly face failure, but that can reliably produce medicines that matter with reasonable cadence. The speed and efficiency of the BridgeBio engine is only possible because we target well-described genetic diseases at their source. It's also the product of our decentralized hub-and-spoke model that is fueled by our tireless employees that are dedicated to making an impact to the patient communities that we serve. I'd now like to highlight some of the most remarkable aspects of the data we have shared over the last few days and encourage those seeking to learn more to access our webcast on each readout. On Monday, we read out our Phase III FORTIFY trial of BBP-418 in limb-girdle muscular dystrophy type 2i. The study exceeded all of our expectations, meeting all primary and secondary interim analysis endpoints. The primary endpoint, glycosylated alpha-dystroglycan was successful to a high degree of statistical significance. Though even small changes in ADG have been shown to be clinically meaningful, it is remarkable to see some patients attaining normalized levels of ADG. And the 80% increase in glycosylation meaningfully moved patients to healthier levels of muscle function. Across the key clinical endpoint studied, ambulatory function and pulmonary function, BBP-418 not only stopped the decline that was seen in the placebo, but showed a statistically significant incline in function. Patients are walking better and breathing better than when they started. In addition, this small molecule is distributed systemically, and we look forward to sharing additional data associated with its impact on other tissues, including importantly, the heart muscle. Earlier today, we shared the top line data from our Phase III CALIBRATE trial of encaleret in autosomal dominant hypocalcemia type 1. We saw profound and highly statistically significant normalization across blood and urine calcium as well as highly statistically significant normalization of PTH. Just to reiterate, a vast majority of patients fully normalized urine, serum and PTH levels. As I mentioned on the webcast, when we speak of cures in therapeutic medicine, this is the type of impact we seek. And as I mentioned on our last earnings call, we are moving expeditiously not only to launch this drug, but also to initiate its Phase III in chronic hypoparathyroidism. Here, encaleret in a cohort of 10 patients normalized urine and serum calcium in 80% of subjects within 5 days of dosing. Importantly, this drug brings differentiated promise to the hypoparathyroidism community across at least 3 potential dimensions. First, it's oral. Second, it potentially normalizes urine calcium, the cause of downstream kidney conditions. And third, it might avoid potential downstream bone-associated resorption issues that could require bisphosphonates. Finally and importantly, for both small molecules in LGMD2I and ADH1, we saw a safe profile, supporting their ability to provide lifelong improvement for patients who have no disease-modifying therapies available today. Of course, these data are only interesting to the extent that we can get the therapies into the hands of patients. This is where the ongoing success of Attruby gives me confidence that we can distribute at scale. We have been in the marketplace for nearly a year, and I feel our message is just beginning to resonate. The numbers to support that include the fact that we have delivered 5,259 unique patient prescriptions to 1,355 unique HCPs, generating this quarter $108.1 million in net product sales. In the long term, although our goal is 30% to 35% share by volume, I believe we have the potential to be a market leader. The best point estimates to date on key endpoints at the lowest price point backed by an aggressive research plan support that future. Early performance of Beyonttra in Europe where physicians have been quick to recognize the strength of our data also supports that future. Our partners at Bayer have done a wonderful job prosecuting the acoramidis hypothesis in Europe, closing in on market leadership in Germany with an NBRx of nearly 50% just 6 months into launch. In that geography, among other tailwinds, regulators have also been quick to shut down Pfizer's inaccurate claims of "near complete stabilization." On that topic, as I was putting together my comments, I stumbled upon an old e-mail that Dr. Jeff Kelly, the inventor of tafamidis, had sent to Dr. Isabella Graef, one of the inventors of acoramidis. In it, and I directly quote him, he says, "given the variability in stoichiometry in the experiments between tafamidis and AG10 and TTR, the data always tell the same story that AG10 is better than tafamidis as would be expected from the determined binding constant." I have to say I agree with him. Moving on from competing, we are also asking ourselves what is unique about our product. As many of you know, in patients with cardiac arrhythmic involvement, we observed a 43% reduction in risk of CVH associated with cardiac arrhythmia and a 17% reduction in TEAEs related to new onset AFib. That is unique. In patients with the most common variant, V122I, we published a 59% hazard reduction, which to our knowledge is the largest point estimate in terms of reduction demonstrated in the field. We expect to further elaborate on these data at the upcoming AHA conference, so please stay tuned for that later this weekend. Additionally, we've continued to interrogate what in my mind is an incredibly unique factor, our early time to separation. In a recent JACC paper, we published that the effect of acoramidis on recurrent and cumulative cardiovascular outcomes was observed as early as 1 month. One question is, why is this prompt effect occurring? One hypothesis is that the answers may reside in the cardiorenal axis similar to what has been described for SGLT2 inhibitors, and we intend to explore this further in the clinic. In addition, we intend to bring a new clinical CMR study to the field to further interrogate Attruby's impact on disease regression as measured by cardiac function and structure. Some of you may have seen another single-site CMR study recently published by [indiscernible] in which they suggest the "potentially superior effect of acoramidis" versus tafamidis on important parameters like LVEF and LV mass. These new research areas marry nicely with the continued execution of our ACT-EARLY, a potentially profound study that explores the effect of acoramidis in presymptomatic variant patients and in the context of this mass action disease. Finally, we'll continue to study the efficaciousness of the drug in the context of real-world evidence studies. We've been proponents of leveraging RWE as early as the survival studies done by Dr. Masri, Moore and others. Given that in the modern marketplace, it is an exceptionally difficult thing to conduct double-blind head-to-head studies, RWE will serve as an important tool in identifying the right patients for the right drug. and we'll have more to publish on this front in the months to come. These research efforts tie together with the continued strengthening of our access profile and increasing diagnosis rates of patients with ATTR cardiomyopathy. Matt will have more to say about our access program, but we continue to offer best-in-class programs and are improving with every month the ability to "make it easy for those patients and physicians that desire access to Attruby." I'll end with a brief comment on future growth. The obvious growth in our portfolio today sits with the expansion programs of hypochondroplasia and in chronic hypoparathyroidism, branching from our achondroplasia and ADH1 programs, respectively. But shareholders should not overlook the deep ownership and close oversight we have with our sister companies. At GondolaBio , in particular, we now have 17 programs across the Mendelian landscape, including what we believe to be a potentially best-in-class asset in EPP in Phase II and buttressed by exciting programs in alpha-1 antitrypsin deficiency, hereditary pancreatitis, ADPKD and many other areas. As these programs move forward and we continue to solidify BridgeBio, we can access new growth opportunities at the right time to increase the scope of work we are doing for patients. With that, I'll turn it over to Matt, our Chief Commercial Officer.

Thanks, Neil. I'm excited to share our Q3 progress and discuss some of the positive trends behind Attruby's continuing success, along with the excitement that the new Phase III data from both encaleret and BBP-418 have created. Starting with Attruby, as we have seen throughout the year, the ATTR-CM market continues to expand with growth coming from all segments of the market. We've been particularly encouraged by the increase in prescribing from both returning and new physicians with a steady rise in first-time prescribers adopting Attruby in their practice. Importantly, once physicians begin prescribing Attruby, they continue doing so, a clear reflection of the consistent clinical performance we've seen in real-world use. This persistence stems from Attruby's differentiated profile of being the only near-complete stabilizer on the market versus a partial stabilizer and a partial knockdown. Attruby has also shown the fastest time to separation from placebo to date. While patients are getting diagnosed faster and at a younger age, many continue to go undiagnosed or progress on their current medications. When that happens, they need something that can stabilize the tetramer and do so quickly. The bottom line is that patients and physicians want a medication that works well and works fast and Attruby continues to deliver on both efficacy and speed. As we look towards Q4 and the 1-year anniversary of the launch of Attruby, there are several factors I would like to highlight. First, Attruby's strong launch trajectory continues to demonstrate consistent growth across all market segments. We expect this momentum to carry into the coming quarters, positioning Attruby for meaningful share expansion over time as awareness and adoption continue to increase. Second, the ATTR-CM market itself continues to grow quarter-over-quarter with no signs of slowing. This ongoing expansion effectively enlarges the total opportunity that Attruby is competing for and supports a sustained growth runway for the brand. Third, as the U.S. health care environment becomes increasingly cost conscious, Attruby remains the least expensive option in the ATTR-CM market. Combined with being commercialized by a U.S.-based company, this positions Attruby well for long-term competitiveness as pricing and access pressure continue to evolve. Finally, we continue to see encouraging underlying trends for Attruby with continued growth in the total number of patients on therapy and a steady increase in ongoing treatment utilization. Together, these trends underscore growing prescriber confidence and sustained demand for Attruby. Building on the momentum from Attruby, we are now turning to the next wave of potential launches in our pipeline. Let me begin by reinforcing how excited we are by the recent readouts for BBP-418 and encaleret, which represent one of the most remarkable dual clinical successes in rare disease drug development. Both encaleret and BBP-418 exceeded expectations across their primary and secondary endpoints, positioning each as a potential first and best-in-class therapy with a compelling value proposition. Together, these programs will redefine care for patients with anticipated strong support from the clinician and payer communities based on the strength of each respective data set if approved by the FDA. We expect an additional readout for infigratinib in the first half of 2026 and look forward to discussing the commercial opportunity at that time. The launch of Attruby has provided invaluable experience in scaling rare disease commercialization from building disease awareness and engaging HCP networks to executing patient identification and access strategies. These learnings are directly informing our next wave of launches, including encaleret, BBP-418 and infigratinib. Many of the same leadership, operations and market access teams who drove the success of Attruby are already in place to support these programs. In preparation for these upcoming launches, we have continued to expand disease state education initiatives and have begun hiring key commercial leadership positions. The response to our initial positions has been remarkable, underscoring both the strength of the BridgeBio platform and the excitement around our pipeline of transformative therapies that will meaningfully improve outcomes for the communities we serve. The hiring momentum will continue to ramp over the next several quarters, leading into the respective potential approvals for each indication. Importantly, encaleret and BBP-418 will represent first-in-class options in their indications, while infigratinib would be the first daily oral medication in achondroplasia, allowing children a needle-free option for their daily care regimen. Beyond the U.S., we're actively building the infrastructure to support global commercialization, enabling coordinated launches and sustained access. Through our expanding global footprint, we are well positioned to deliver meaningful innovation to rare disease communities worldwide, ensuring global access, continuity and impact. With that, I will turn it over to Tom, who will discuss BridgeBio's financials.

Thank you, Matt, and good morning, everyone. I'll now discuss our financial results for the third quarter of 2025. Please note that our commentary on today's call will focus on GAAP financials unless otherwise indicated. Total revenues were $120.7 million in 3Q 2025, consisting of $108.1 million of Attruby net product revenue, $4.3 million of royalty revenue and $8.3 million of license and services revenue compared to $2.7 million of the same period last year. The $118 million increase in total revenues was primarily due to a $108.1 million increase in net product revenue from Attruby driven by strong growth across all market segments. We also recorded $4.3 million in royalty revenue from ex-U.S. net sales of Beyonttra in Europe and Japan. Total operating expenses for the third quarter of 2025 were $259.3 million compared to $193.9 million in the same period in the prior year. The $65.4 million increase in operating expenses was primarily driven by a $68.8 million increase in SG&A expenses, partially offset by a slight decline in R&D expenses. This reflects our continued investment in the Attruby brand awareness and ongoing investments in our late-stage clinical programs. Turning to our balance sheet. We ended the third quarter with a strong cash position of $645.9 million in cash, cash equivalents and marketable securities, which provides significant cash runway to continue supporting our transition into a diversified late-stage multiproduct business. In closing, our commercial launch of Attruby continues to accelerate, and our pipeline has never been stronger. Following the positive results from LGMD2I/R9 and ADH1, we now look forward to top line results from achondroplasia in early 2026. With that, I'll turn the call back over to Chinmay.

Thank you, Neil, Matt and Tom. We will now turn the call over to the operator, who will open the line for questions. We kindly request that you limit yourself to 1 question. Thank you.

[Operator Instructions] Our first question will come from the line of Salim Syed with Mizuho.

Congrats on all the week's successes. Neil, Matt, maybe this one for you. Possible to comment on the percentage of new patient share. I know last time you provided the number, I think it was 18% to 20% on the 2Q call. Just wondering if that's increased since then. And if that remains the primary focus for growth? Or are you also seeing an increase in the switch category?

Yes. Salim, good question. I'll take a crack and Matt, you can elaborate if I miss something. I mean I'd say our naive share, it's hard to tell, honestly, because we don't have all the numbers yet from Alnylam and Pfizer for the quarter. But our best guess is that the naive share is well in the 20s now. We've seen double-digit growth, obviously, in overall script quarter-on-quarter number, and that script growth has been even more profound in the NBRx setting. That means that we've seen a little bit of a downturn in the switch setting, and that's mostly because we're seeing a lot of combo use. There's some work that we could do in terms of reminding people that why not use the best stabilizer on top of a knockdown if you're going to go that route, but our NBRx share continues to grow nicely. Why do we focus on that? I mean, you know this as well as I do. But ultimately, your peak steady-state share is pretty simple, right? It's a fraction of new patients that you're capturing multiplied by the fraction of the total market that is new each year divided by the annual dropout rate. And if you look at this marketplace, the annual dropout rate is pretty high, something like 40% is what we modeled when you certainly look at Pfizer. And the fraction of the new markets that are adding patients to the market, it's not just replacement over time is going to be greater than that. So any time those 2 things are -- effectively, that fraction is greater than 1. What you ultimately want to do is maximize a fraction of new patients that you capture. So whatever if it's at 30%, then we're going to be a multiplier of that on peak year share. So -- as we look forward over the course of the next 3 to 4 years, obviously, our goal is 30-plus percent market share. We're well in range to do that even with the numbers that we have today, and I expect them to continue to grow.

Our next question comes from the line of Tyler Van Buren with TD Cowen.

Congrats on another solid quarter of Attruby commercialization. So could you elaborate on the ATTR cardiomyopathy diagnosis rates and if you're continuing to see momentum build since the launch? And forgive me, but I have to ask a second one. So there are some centers that might prefer AMVUTTRA as they collect money on a much higher ASP despite the cost that it adds to the system. So curious to get your thoughts on that market dynamic. Do you expect this to impact a minority of the centers and patients -- and is it something that you have to adjust your strategy to in those centers?

Yes, 2 great questions, Tyler. Thanks for them. And I would say just in terms of market growth, again, until we get the full revenue numbers from Alnylam and Pfizer, I won't know precisely or be able to back into precisely the number of scripts on the quarter. But I can say pretty reliably, if you go back 1 year, so quarter and what that looked like this quarter last year, there's been a pretty robust and continued growth in diagnosis. Certainly, what we're seeing in the field is a lot of growth in diagnosis. new practices, as you can see from our ACP data as well as doctors finding more of these patients. I think the PYP reimbursement concerns were overstated. We don't see that being a drag in terms of people finding new patients. And there's a lot of excitement and education going on in and around this category. If you go to any of the conferences, and I'm sure the same is going to be at AHA, these sessions are packed. People are keen to learn more about ATTR cardiomyopathy. And with all the publications ongoing, there's a lot of people who want to throw their hat in to be part of the next wave of learning in this space. So I expect that diagnosis rates will continue to increase and get us closer to that 250,000 that ultimately we should get to in the U.S. Second question on the buy-and-bill dynamic. I mean it's not -- I don't think we have to adjust our strategy because we always knew that, that was going to be the case. Certainly, there are certain centers of excellence that if you have a reasonable CFO at a hospital system, you're going to be 340B pricing. And so there's a lot of profit that one can take. from that. But I would say, writ large, unlike rheumatology, when you get out into the high-volume heart failure practices, this is not a meaningful part of the profit center associated with those practices. And so you're not see a lot of cardiologists just looking at buy-and-bill as the way to make more money. So we haven't seen that. And overall, I would say, amidst the specialty community, you see just a lot of focus on doing the right thing in terms of data efficacy, in terms of safety and ultimately in terms of cost. Right now, you're seeing a lot of combo use. You're seeing some centers do a lot of super high-priced drug use, but I even hear physicians within those centers saying, I'm not sure I should be putting someone on $1 million worth of therapy if indeed there's no data to back up the fact that, that's more efficacious than a low-cost small molecule like ours. So I think, again, in the long term, as you saw in the TNFs and other buy-and-bill type things, the combination of good data and what payers will ultimately do as they control this category more, I think, will drive certainly that NBRx share up for the small molecule stabilizers as compared to the high cost with worst point estimates, knockdowns that are buy and bill.

Our next question will come from the line of Biren Amin with Piper Sandler.

I got to say it's the first to have 3 positive investor calls by a single company in 1 week. So congrats on that. My question, you talked about market access as a top priority for the company. Thoughts on Pfizer matching the 28-day free trial with VYNDAMAX, any impact from this program that you foresee?

Yes. Great question, Biren, and thanks for the compliment there. We see it as a positive. Anytime you actually roll out a program that's generous to patients, I assume our competition is going to match it. And ultimately, it gets us thinking about what else we can do. I mean, I think if you look across the totality of our programs, they continue to be the most generous in the space. But overall, we welcome that type of competition. It shouldn't really be access ultimately that's driving the differential share that we gain. Ultimately, all we want is an even playing field, and that's what we've been talking about writ large across the payer and provider landscape and then ultimately to let our efficacy data speak. If you add anything?

No, I think that's exactly right. It's it's not a bad thing when someone copies a good program. And so in terms of it impacting, I don't think we've seen an impact from it. It's -- when you're the first one to do it, I think people remember that one maybe a little bit more, but we were happy to see them offer that. Any competitor ought to be thinking about doing the same thing, whether it's the free drug for life that we did for our patients in the clinical trial or with the 28-day free trial. So I think...

Maybe one final thing, Biren. Obviously, our LDN is completely differently designed than theirs and the entirety of the patient and physician experience is pretty different, not just because of some of the programs that we rolled out. So I'd encourage you to go and hear from patients and physicians, just how quickly are they receiving therapy in the context of our drug and how easy is it for them to continue on the drug product. regardless of the programs that are put in place, just the way we've designed this with a high-touch, white glove rare disease approach has meaningful advantages.

Our next question comes from the line of Mani Foroohar with Leerink.

You have Ryan on for Mani. Congrats on the quarter. Maybe just could you talk about how you see the size of the OUS opportunity relative to that of the U.S. and ATTR, particularly as those launches start to ramp up?

Yes, I can take that, and Matt, you can elaborate on it. I think the OUS opportunity has been quite interesting, obviously, as I mentioned in my outset comments, Bayer has done a very, very nice job in the countries that they've commercialized in to date. What makes it interesting, obviously, is ultimately, in some ways, they're able to fast forward to what I think the ultimate answer is in the United States, which is accurate advertising, obviously, issuing some of the incomplete statements around near complete stabilization that our competitors have. And I think secondly, a lot of the experts are able to look at the totality of the data and understand from a health economic real-world evidence standpoint, which therapy should be used frontline and which therapies should not. So I think we're relatively advantaged in that marketplace in terms of share. Where we're not advantaged, obviously, from an overall market standing standpoint is the price point. The price point is going to come down as we move from some of the countries we're already commercializing in countries like the U.K. And so ultimately, I expect to see the ratio of sales between Europe and the U.S. to be pretty similar to what we see in TAF. But again, I think Bayer has done a really nice job of accelerating some of those market dynamics in Europe in ways that we simply can't do given the current status of the playing field in the United States.

Our next question will come from the line of Josh Schimmer with Cantor.

Quite the weak for you guys. Have you had any discussions with payers regarding what might happen to formulary positioning of Attruby when TAF generics do enter? And separately, have you discussed with payers the use of combination therapy as it stands now? I'm a little surprised they're on board with it given the cost and the lack of data.

So no, to the first question, we've been focused on Attruby solely and really getting it as on equal playing field with TAF and to date. I think on the second, we also haven't had conversations around combo therapy. I think we've had conversations with physicians around it, and I expect that payers will do more to control this category as we move forward. But right now, the mechanisms of B versus D and things of that nature make it, I think, a slow-moving train in that respect. It will ultimately happen, but I don't think it happens in the next 6 to 12 months.

Yes. And I think we just really remain -- as Neil said earlier, we just remain focused on making sure Attruby is available to any patient who wants it. And as long as that is out there, we feel really good about our data, and we can fight it out in the doctor's office versus trying to fight it out in the payer space.

Our next question comes from the line of Cory Kasimov with Evercore.

So your prepared comments noted the impressive growth, both in unique prescribers as well as prescriptions per prescriber. Can you talk about what's primarily driving that momentum, whether it's the greater penetration within existing accounts, expansion into new centers or improved conversion rate?

Yes, I won't break it down quantitatively, but it's actually kind of equivalently both. And I would say one interesting piece is a lot of these new prescribing HCPs are effectively capitated parts of a center of excellence or the referrers into centers of excellence. One thing we were finding early on were some centers of excellence where our share might not have been as high. When we went and spoke to the physicians, they would say, yes, we believe that Attruby is a stellar drug, and we would like 30%, 40% of our patients to be on it. But if a patient comes in already on TAF, we're not going to change them. And so it behooved us to get out to those practices that we weren't covering. We have a smaller sales force than does Pfizer or Alnylam. But we've started to do that, and we've employed some IT techniques as well so that we get sort of alerts anytime someone is prescribing. And we're just getting to know some of those what people call ancillary or satellite practices better. So both things have been driving the scripts.

Our next question comes from the line of Anupam Rama with JPMorgan.

Just 2 quick ones for me. Just I'm wondering what the marketing message is around -- to docs around patients with mixed phenotype for Attruby. And then actually a higher-level strategic question. After the first couple of days of this week, like the path to top line diversification here is pretty clear, and I know we're waiting on infigratinib. But Neil, maybe following on some of your prepared comments, how should we be thinking about investments into kind of the early-stage and mid-stage pipeline? And when do we learn more about those programs and catalyst time lines and things like that?

Yes. Thanks for those questions. On mixed pheno, honestly, we don't see -- I mean, this is more of a question that we get from investors than we do from physicians or in the field. For the most part, the patients that we serve have to do with cardiomyopathy, and that's the salient set of characteristics that drive their mortality and morbidity. In and around mixed phenotype, the best thing we can do is continue to hammer our variant message. Obviously, variants are where you get mixed phenotype, you don't get mixed phenotype within the context of the wild-type population. And as we suggested in our prepared comments, we continue to, I think, publish the most impressive data within the context of the variant population, that 59% hazard reduction, I think it's the largest point estimate and the only statistically significant point estimate in that space. Again, stay tuned for some of the things that we're going to be publishing at AHA, but I think it builds on that within the variant population. And all of that connects back to the fact that biochemically, we have a differentiated binding profile for those variants. And I think if you look at the JACC paper associated with the AMVUTTRA trial, you can see that they didn't quite do in variants what people suspected they might in terms of a differentiated efficacy. So we continue to believe we have the most efficacious profile within that space and the V122Is are going to be the most common of the variant population that we see. I would say, finally, just on that variant population, it's just another good example of how we're trying to really view Attruby as a unique property and look to see whether or not we can in presymptomatic patients, intervene early so that they can stave off future heart failure altogether, and that's that ACT-EARLY trial. So I think we're doing quite a bit to address that marketplace. Secondly, just in and around top line diversification, I'd say, first and foremost, we're laser-focused on nailing the launch of the 2, hopefully, the third product to come here in early next year. Three launches for any company, I think, is a big thing to do, and it's going to be big for BridgeBio here for us to stick it. Obviously, it's going to be a couple of first-in-class launches and then another competitive launch. So a couple of different characteristics as we build out our commercial muscle. That being said, this is maybe -- save 8, 9 years ago, the most interesting time to do research and early development in rare and orphan disease, almost no competition, to be honest. And the scientific tailwinds are, I mean, nothing short of mesmerizing. You're reading the journals, Anup, I know, just as I am, but the pan-genome, long-read sequencing, what we're learning about non-coding regulatory regimes, all of that is really suggesting a wide variety of new targets we can go after to help patients in profound ways. And that's why the buildup of some 17 assets in the context of Gondola. And I would say, again, as Bridge shareholders, there's 0 information asymmetry between those 2 entities and a high degree of ownership that Bridge has into Gondola. So at the right time, again, when shareholders and the Board and management are aligned that we have capacity, I think we have growth that we can access from there. And by the way, we're looking across the industry right now. There are several other entities out there that may be deprioritizing rare and orphan disease because investors don't view it as high a priority as I&I or certain areas of oncology. And where we do view it as attractive, we can be a reasonable partner all the way through the life cycle of early research all the way to commercial. So the aperture is pretty broad right now. I'd say the competitive intensity is pretty low. So at the right time, I think we'll be able to return to growth in terms of programmatic growth in the right way. But we got to stick the landing on these launches first.

Our next question will come from the line of Andrew Tsai with Jefferies.

Congrats on the strong execution. My question is around -- back to Attruby. You're accumulating a lot of real-world evidence suggesting better efficacy over tafamidis. That's great. But I'm curious what your guys' thoughts are in doing a head-to-head study to fully prove that out. I'd also imagine that could help mitigate against any risk of a future tafamidis generic, so kill 2 birds with one stone.

Yes. I mean, I think great question. Thanks for the question. A couple of comments there. Number one is, I think we've been doing a lot of this sort of head-to-head competitive. We are a better stabilizer across the 4 in vitro assays across every single serum TTR measurement that we've seen across NT-proBNP, across whatever point estimates we can look at where you can line things up, it appears that we are a better stabilizer and that better stabilization leads to better outcomes. I'm not so sure that, that is going to continue to resonate with the clinical community versus kind of the area that we're set off now in, which is describing what's unique about our property given the fact that it is an ever more potent stabilizer. So some of the things you're seeing in terms of publications in the variant population in terms of AFib and the cardiac arrhythmic population, some of the things that we'll be looking at in terms of the cardiorenal axis, those are all completely unique. And I think aspects of the compound that are -- they won't easily be matched by the other therapies in this space. So I would say that's one thing. The second thing is the double-blind head-to-head is something that I still think about a lot, but the double-blind head-to-head that's doable for us at this size is a double-blind head-to-head against serum TTR, which we obviously win, and I'm not so sure it drives any market share or a double-blind head-to-head against NT-proBNP, which I also think we will pretty obviously win. But also, I'm not sure it would drive a ton of market share. And the reason I say that is I think people are really -- they think about different patient populations, what patients want. When we talk to our customers, they're not looking for a double-blind head-to-head to say this drug product is definitively the one I'm going to use in every case. And a good sort of eye-opener on that was the JACC paper that AMVUTTRA published. But if you really cared about double-blind head-to-head, you look at the vu arm and you look at the TAF arm, both monotherapy, and you see that they deliver the exact same results. And by the way, acoramidis beat TAF everywhere we looked in our trial. And that was actually baselines were very, very close in the HELIOS-B trial. So if people really, really cared about these like head-to-head type studies, they would look at that data and scratch their heads and be like, what's going on? Obviously, what's going on is that the PK of knockdown starts in the 60s and ultimately gets to the 80s only after 22 months for AMVUTTRA, and that's probably why it doesn't outperform TAF in that HELIOS-B characterization. So I'm not so sure that spending $300 million or whatever, $400 million and et cetera, et cetera, to run a double-blind head-to-head would do much here. And then finally, you and Josh both referred to TAF generic, and I'm not going to make any comments on timing there, although I have a view that I think most of you know. But even if it does go generic and Pfizer determines that they don't want to defend this property in any way, shape or form, I mean, look, we're basically a generic in terms of pricing as compared to AMVUTTRA. I don't see payers stepping in and saying, you can't use this drug or you have to step through this drug, certainly in the United States anytime soon and especially given the differentiated data that we have already presented. And the final point on that is I really do think real-world evidence is -- I mean, you talk to the FDA, you talk to a lot of clinicians these days. They're very keen on understanding how these drugs perform in the real world. And so I think a lot of differential work that we do will be associated with real-world evidence. And I think a lot of that will actually be pretty impactful for the prescribing universe we look at, maybe even more impactful than a very specific clinical trial. So those would be my comments on that.

Our next question will come from the line of Danielle Brill with Truist.

And since we're going to expect a positive Phase III, maybe I'll pivot and ask a question on infigratinib. Neil, what are the most important differentiating elements for infigratinib in achondroplasia in view? Is it more about efficacy or route of administration? And can you talk about safety and how important that is? What level of hyperphosphatemia is acceptable in your view?

Yes. Great question. One thing I've learned from Matt and others now having a commercial franchise is that the customer is always right, and you can never really tell why a customer may prefer one drug product versus the next. That's what makes market share relatively hard to project in the absence of head-to-head -- double-blind head head-to-head trials. The good news here is that we're more efficacious, we're safer and we're more convenient with an oral ROA. So whatever your preference in terms of why you're determining which drug to use, infigratinib is going to win. As a scientist, obviously, down deep, I would prefer the most efficacious product win. And I think we've already demonstrated and we'll continue to demonstrate superior efficacy. Why? Because, as you know, this targets this well-described condition at its source, addressing both of the salient effector signaling pathways. It's superior in every preclinical model. It's superior in animal models. It's superior in Phase II data. It's the only product that's provided proportionality impact. And I think over the longer term, we'll provide a broader diaspora of impact for this community that we serve as compared to the CMP products. So I don't think there's any aspect. We obviously don't see the hypotensive results, and I don't think we're going to have as robust a Section 4 as the CNP products have in terms of safety. I think this will be a safer product. Grade 1 hyperphosph, I think it could be 15%, 20% could be -- like people do not care about that as much as the Street cares about that. Again, what they do care about are things that ultimately would be things associated with hypergrowth, spinal situations, things of that nature. And we see no evidence of any safety issues in and around that. So I think the drug will be more efficacious, safer and ultimately more convenient. And I think that will open up the market, which obviously is starting to stagnate a bit given the current profile of the drugs. I think we can continue to address unmet need. And I think however you want to slice and dice it, we'll have a great offering for the community here.

Our next question will come from the line of Jason

On all the progress. Maybe to connect some of the dots from your previous comments here, I mean, in thinking about infigratinib as a growth driver, I mean, you've guided to opportunities of $2 billion each in achondroplasia and hypochondroplasia. Can you walk us through some of your key assumptions here given the competitive landscape? Is this more that you're capturing share from a competitor? Are you growing the market appreciably? I mean what gives you confidence in both of these numbers?

Yes. I mean I think, first, we do tend to estimate these numbers starting with the treatable population and making assumptions in and around there. Certainly, in the context of an already launched product, we're going to be looking to both take share as well as to grow the market. I think it's important to realize that there are substantial parts of the unmet need here that aren't addressed by once-daily injectables. We've heard that when we go out into the community. We've heard that in talking to physicians. I think it's a bit unfair to look at the market sometimes with a suboptimal therapy and conclude that, that is the market size. I play in EPP as well, and I wouldn't look at CLINUVEL's product and determine that EPP is an extraordinarily small market. So I think the unmet need is relatively well described in terms of numbers of patients. And it's not in the context of this condition that we don't know how to find the patients and that they are not already well identified. So I think it just comes down to offering them something that they want, and I think this could be that from our research.

Our next question will come from the line of Paul Choi with Goldman Sachs.

Congrats on the string of good news this week. I also want to stay on the topic of achondroplasia, Neil. And as you know, the current approved product is 3/4 of the sales are coming from ex-U.S. with only 1/4 of the sales from the U.S. market. And so could you maybe comment on what could be market expanding for the U.S. market in particular here? How large -- you talked a little bit about the TAM, but just sort of what are the key factors from market expansion happening here? And then in terms of the product, just sort of how much you think incremental the hypochondroplasia opportunity could be to your infigratinib sales?

Yes. Thanks, Paul. I'm a bit remiss to comment on the commercial tactics or performance of one of our competitors. There's nothing in and around the unmet need, the physician community or the community affected with achondroplasia that's starkly different between Europe and the United States. And so I think, again, a solid therapy could work well in both markets. And I'd expect actually the normal ratio that you see with drug products to be true in the context of this category as well. So why the launch hasn't gone that well for our competitor in this case? I mean, number one, I go back to injectables. We do hear a lot of needle phobia, particularly in the U.S. markets, which we know better since we're a U.S.-based company. So we talk a lot to folks here, and I think there is a reasonable amount of needle phobia. I can't comment on the way that they've targeted and their commercial sales force, but recall that in Europe, generally, you have centers of excellence that have taken on a higher percentage of the population in any given geography. So it's easier to identify precisely who to call on and when to call on them. So I think the dynamic could -- that could lead to a slower ramp for them here in the United States. But again, I just go back to the treatable population, both for hypochon and achon. And I think that even under conservative assumptions, this is a large unmet need that then translates into a reasonably large TAM.

Our next question will come from the line of Martin Auster with Raymond James.

This is Thomas on for Marty. I want to add our congrats on all the news this week. I actually want to circle back on the CALIBRATE data this morning. Could you provide any more detail on the serious treatment-related adverse events observed with encaleret in periods 2 and 3? And anything to say about those on standard of care in period 1 as well would be helpful.

Yes. So this is really a -- I mean, it sounds serious, serious related TEAE is a serious thing. But in the context of these drugs, it's all hypercalcemia. So basically driving calcium levels in the serum higher than what you had intended. And in the case of the standard of care, it actually was quite high. Again, like standard of care is taking calcium. So this does happen. You titrate it. In this case, the patient had to go in to the hospital and received IV fluid until that blood calcium was decreased. Actually, in the case of encaleret, it was much milder. It was a very mild digression into hypercalcemia, but that patient had some altered mental status and UTI, obviously, nothing to do with the drug at all. So that's what took them into the hospital and they were dosed down, no discontinuation. So again, I think the most important part here is that the drug is probably -- we saw less discontinuations on drug than we did on standard of care. So the drug is safer than standard of care and obviously driving 76% normalization versus less than 5% that's profound. And I think in large part because you've got an allosteric mechanism that very precisely targets the calcium sensing receptor. So very much like Attruby or acoramidis, when you've got something like that, you've got a small molecule with a very specific target, not likely to have a significant side effect profile.

Our final question will come from the line of Trevor Allred with Oppenheimer.

Congrats on the quarter. I wanted to follow up again on encaleret as well. Can you give us -- can you talk a little bit more about what gives you confidence in encaleret as a $1 billion-plus product? And can you talk a little bit about your expectations for the potential upside opportunity in chronic hypopara?

Yes, sure. I guess I don't necessarily like to talk about things in terms of the dollar amount, but I'm curious what's your price assumption? We haven't determined the price, but what will be your pricing assumption on encaleret for ADH1?

I think I'm in the range of $200,000.

So less than Yorvipath?

Yes.

Why?

I mean it could be more than that...

That's like 8x or 10x the population. Anyway, that's an extremely low number. I've not heard that. But let's just put it in a normal rare disease context of whatever, $300,000, $400,000, $500,000 in that range, you're talking about a couple of thousand to 3,000 patients on drug to achieve the touch of numbers that you put forth. And we always start with prevalence here. Obviously, the prevalence is much higher than the identified population. But the thing -- and I think in large part due to like what happened over the last 5 or 6 years, where everyone claimed every large -- every genetic disease was a super large disease. Recall, this is not SCITX1 OR GACI or one of these conditions that severely limits lifespan. For those conditions, I think over -- you take the number and then people apply the genzyme factor and say, it's going to be 4x larger, not usually because those children aren't necessarily having children. Most of those mutations are germline. Those are very, very constrained populations. Same would be true, for instance, for Canavan disease, which is another disease we work on. It's not going to be a large population. It just -- it makes no epidemiologic sense that it would be. In this case, totally different, a large population, mostly germline that even when untreated, allows people to go on and have children. Obviously, 2, 3, 4 different studies that we and others have conducted suggesting a prevalence of up to 12,000 in the U.S. That's not going to be off by an order of magnitude, 1,000 people on the ICD-10 code, 3,500 patients already identified. And an easy way to identify them in terms of going and looking at the nonsurgical hypopara community and doing genetic testing is another tailwind that I believe allows us to believe that we could get a few thousand people on this drug. I think importantly, the guidelines are already in place to suggest that for nonsurgical hypopara patients, they get genetic testing. And so it's up to us to really drive that into the community. I'm not going to suggest that it's going to be a quick launch because we have to educate. We have to ultimately get physicians to work into their work protocol, the fact that they're genetic testing and even in the cases, as you know, of BRCA or targeted cancer therapy, sometimes you can see as little as 40% testing in the community. So it's up to us to ensure that we work with the right providers and make sure that people are looking for ADH1 where they ought to be looking. But I would say the final thing that gives me hope that we can start to identify these patients and get them on product is just how good the drug is. When you're talking about less than 5% response on standard of care, you're talking about a lifelong set of symptoms like fatigue, brain fog, seizures. I mean this is -- I know a lot of people in the rare disease world think if people aren't passing away from the disease, it's not severe. This is like way more severe than having acne every day or losing your hair, both of which I have. But I mean, this is really life-destroying. And so 76% response rate, full normalization, getting close to a therapeutic cure for a majority of patients. That's the type of thing that I think will drive physician excitement and patient excitement and will allow us to find a reasonable fraction of these patients.

And that will conclude our question-and-answer session. I'll hand the call back to Chinmay for closing comments.

Thank you, everyone, for joining us for our Q3 2025 earnings call. We appreciate the interest and look forward to updating you on the progress of our company in 3 months. Thank you.