Earnings Call Transcript - BBIO Q3 2025

Operator, Operator

Good afternoon. I will be your conference operator today. 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.

Chinmay Shukla, Senior Vice President of Strategic Finance

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 will 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.

Neil Kumar, CEO

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 two 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 over 30 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 two stellar Phase III top-line results over the last three days. It is quite the coincidence that these readouts happen to stack on top of one another after over six 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 ten of our updated corporate presentation shows the industry-leading timelines that we have been able to achieve, and slide eleven shows the remarkably high probability of technical success across our programs across the nearly ten years that we have been operating. Probabilities of technical success north of 70 percent 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 on 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 percent 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 percent of subjects within five days of dosing. Importantly, this drug brings differentiated promise to the hypoparathyroidism community across at least three 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 percent 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 percent just six 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 email 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 percent reduction in risk of CVH associated with cardiac arrhythmia and a 17 percent reduction in TEAEs related to new onset AFib. That is unique. In patients with the most common variant, V122I, we published a 59 percent 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 one 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 a colleague 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 efficacy 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.

Matthew Outten, 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 one-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.

Thomas Trimarchi, President and CFO

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 Q3 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.

Chinmay Shukla, Senior Vice President of Strategic Finance

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 one question. Thank you.

Operator, Operator

Our first question will come from the line of Salim Syed with Mizuho.

Salim Syed, Analyst

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?

Neil Kumar, CEO

Yes, that's a good question. I’ll take a shot at it and Matt can add if I overlook anything. It's difficult to determine our naive share since we don't have all the numbers yet from Alnylam and Pfizer for the quarter, but our best estimate puts the naive share in the 20s now. We've experienced double-digit growth in the overall script quarter-on-quarter, with even stronger growth in the NBRx setting. We have seen a slight decrease in the switch setting, primarily due to increased combo use. There's potential for us to remind people that using the best stabilizer alongside a knockdown is beneficial if they choose that approach, but our NBRx share continues to increase positively. Why do we prioritize that? As you know, your peak steady-state share is straightforward: it's the fraction of new patients you're capturing multiplied by the fraction of the total market that is new each year, divided by the annual dropout rate. In this market, the annual dropout rate is quite high, around 40 percent as modeled with Pfizer. The proportion of new markets adding patients must exceed that as they’re not just replacing patients over time. Ideally, you want to maximize the fraction of new patients you capture. So if that’s at 30 percent, it will multiply into the peak year share. Looking ahead over the next three to four years, our goal is to achieve over 30 percent market share, and we are on track to do that even with the current figures, which I expect to keep growing.

Operator, Operator

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

Tyler Van Buren, Analyst

Congratulations on another successful quarter of Attruby commercialization. Could you provide more details about the diagnosis rates for ATTR cardiomyopathy and whether you are seeing continued momentum since the launch? Additionally, I have another question. Some centers may prefer AMVUTTRA because they can generate higher revenue despite the additional costs. What are your thoughts on this market dynamic? Do you believe this will affect only a small number of centers and patients, and will you need to adjust your strategy in those locations?

Neil Kumar, CEO

Thank you for the excellent questions, Tyler. Regarding market growth, I won't have the exact revenue figures from Alnylam and Pfizer until we receive their full numbers, so I can't specify the number of scripts for this quarter. However, if we look back at last year, there has been significant and ongoing growth in diagnoses. We're observing an increase in new practices, as indicated by our ACP data, along with doctors identifying more patients. I believe the concerns around PYP reimbursement have been exaggerated, and they aren't hindering the process of discovering new patients. There is considerable enthusiasm and educational activity in this field. Attending any conferences, such as the upcoming AHA, you'll find that sessions are very well attended, with a strong interest in learning about ATTR cardiomyopathy. With the numerous publications continuing, many are eager to contribute to the next phase of understanding in this area. I anticipate that diagnosis rates will keep rising, bringing us closer to our goal of 250,000 in the U.S. Regarding the buy-and-bill dynamic, I don’t think we need to change our strategy since we were always aware that this would be the case. Some centers of excellence will benefit from reasonable CFOs and employ 340B pricing, allowing for significant profits. Nonetheless, generally speaking, unlike rheumatology, high-volume heart failure practices don't rely on buy-and-bill as a significant profit source. There isn't much interest among cardiologists in buy-and-bill as a primary revenue generation strategy. Overall, in the specialty community, there is a strong focus on ensuring data efficacy, safety, and ultimately managing costs. Currently, there is considerable use of combination therapies, and while some centers are utilizing high-cost drugs, even physicians at those centers express uncertainty about the value of expensive therapies without data to support their effectiveness compared to our lower-cost small molecule. In the long run, as seen with TNFs and other buy-and-bill situations, the combination of solid data and payer control will likely elevate the NBRx share for small molecule stabilizers compared to high-cost options with less favorable outcomes.

Operator, Operator

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

Biren Amin, Analyst

I got to say it's the first to have three positive investor calls by a single company in one 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?

Neil Kumar, CEO

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?

Matthew Outten, Chief Commercial Officer

No, I think that's exactly right. It's not a bad thing when someone copies a good program. In terms of its impact, I don't believe we've noticed any effect from it. When you're the first to do something, people may remember that a bit more, but we were pleased to see them offer that. Any competitor should consider doing the same thing, whether it's the free drug for life we provided for our patients in the clinical trial or the 28-day free trial. So I think...

Neil Kumar, CEO

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 it is 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.

Operator, Operator

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

Unknown Analyst, Analyst

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?

Neil Kumar, CEO

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.

Operator, Operator

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

Joshua Schimmer, Analyst

Quite the week 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.

Neil Kumar, CEO

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 six to twelve months.

Matthew Outten, Chief Commercial Officer

Yes. I think we are focused on ensuring Attruby is accessible to any patient who wants it. As long as it remains available, we feel confident about our data, and we can compete in the doctor's office instead of in the payer space.

Operator, Operator

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

Cory Kasimov, Analyst

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 rates?

Neil Kumar, CEO

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 was 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 percent, 40 percent 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.

Operator, Operator

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

Anupam Rama, Analyst

I have two quick questions. I'm curious about the marketing message aimed at doctors regarding patients with mixed phenotype for Attruby. Additionally, after the first few days of this week, the pathway to diversifying our top line seems quite clear, and while we await infigratinib, Neil, could you elaborate on how we should approach investments in our early-stage and mid-stage pipeline? Also, when can we expect updates on those programs, including their catalyst timelines?

Neil Kumar, CEO

Thank you for the questions. Regarding mixed phenotype, we find this is more a concern for investors than for physicians or in practice. The majority of our patients are related to cardiomyopathy, which significantly affects their mortality and morbidity. In relation to mixed phenotype, the priority is to emphasize our message about variants. Variants are what lead to mixed phenotype; it doesn't occur within the wild-type population. As we mentioned earlier, we are eager to publish our robust data in the variant population, including a 59 percent hazard reduction, which represents the largest and only statistically valid estimate in that area. We have more data to share at AHA, which will further support our findings in the variant population. This correlates with our unique biochemical binding profile for those variants. If you examine the JACC paper linked to the AMVUTTRA trial, it shows that the differentiated efficacy in variants was not what some had expected. We remain confident that our profile is the most effective in this space, particularly for the V122Is, the most prevalent among variants. Additionally, with respect to the variant population, we are focused on how we can position Attruby as a unique treatment, especially for presymptomatic patients, to potentially prevent future heart failure, as seen in the ACT-EARLY trial. We are diligently working to tackle this market. On the topic of top-line diversification, we are committed to successfully launching two products, and hopefully a third early next year. Executing three launches is a significant challenge, but it is crucial for BridgeBio, particularly since these will include first-in-class and competitive launches. This diversity will enhance our commercial capabilities. Moreover, I believe this is one of the most exciting times in research and early development in rare and orphan diseases, with minimal competition. The scientific advancements are incredibly promising. We're observing intriguing developments in pan-genome, long-read sequencing, and non-coding regulatory studies, opening many new targets to pursue for patient benefit. This is the basis for our 17 assets in the Gondola initiative. As Bridge shareholders, there is transparency and a strong ownership connection to Gondola. When the timing is right, and alignment exists with our shareholders, board, and management, we can tap into the growth opportunities there. Currently, we see several players in the industry that might be retreating from rare and orphan diseases due to investor preferences leaning toward I&I or certain oncology areas. However, we find these spaces attractive and are positioned to become valuable partners throughout the early research and commercialization phases. The competitive landscape is relatively low at the moment, suggesting that when conditions are suitable, we can return to programmatic growth effectively, but our priority is to successfully execute these launches first.

Operator, Operator

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

Lin Tsai, Analyst

Congratulations on the strong execution. My question is about Attruby. You're gathering a lot of real-world evidence indicating better efficacy compared to tafamidis, which is great. I'm interested in your thoughts on conducting a head-to-head study to fully demonstrate this. I also think that could help reduce the risk associated with a future tafamidis generic, achieving two objectives at once.

Neil Kumar, CEO

Yes, that's a great question. Thank you for asking. First, we've been engaged in significant head-to-head comparisons. Our product demonstrates better stabilization across all four in vitro assays for serum TTR measurements, including NT-proBNP, indicating we outperform in this area, leading to improved outcomes. However, I’m unsure if this will resonate with clinicians compared to focusing on the unique aspects of our product as it proves to be a more effective stabilizer. Recent publications in the variant population, particularly regarding AFib and cardiac arrhythmia, highlight unique features of our compound that are not easily matched by other therapies. Regarding double-blind head-to-head studies, while I think about them frequently, what we could realistically pursue is a comparison against serum TTR, where we know we would excel, or against NT-proBNP, which we also expect to win. However, I don’t believe these comparisons would significantly impact market share. Discussions with our customers reveal that they are not seeking a definitive head-to-head study that dictates their choice of drug in every situation. For example, the JACC paper on AMVUTTRA indicates that both the vu arm and the TAF arm yielded similar results in monotherapy. Moreover, our studies showed that acoramidis outperformed TAF across various metrics, even though the baseline characteristics were closely aligned in the HELIOS-B trial. I question whether investing $300 million to $400 million in a head-to-head study would yield meaningful results. Additionally, regarding TAF generics, while I won't comment on timing, I believe even if a generic emerges and Pfizer opts not to defend their position, we are effectively priced competitively against AMVUTTRA. I doubt payers will restrict access to our drug in the near future, particularly given the distinct data we have shared. Finally, real-world evidence is becoming increasingly important. Conversations with the FDA and clinicians show a strong interest in understanding how drugs perform outside of clinical trials. I believe our work in this area will carry significant weight in influencing prescribing practices, potentially even more than traditional clinical studies. Those are my thoughts on the matter.

Operator, Operator

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

Danielle Brill Bongero, Analyst

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?

Neil Kumar, CEO

Yes, that's a great question. From my experience with Matt and others in the commercial sector, I've learned that the customer preferences can be unpredictable, making it difficult to forecast market share without direct comparison trials. The positive aspect is that our product is more effective, safer, and easier to take as it is administered orally. Regardless of individual preferences for drug selection, I believe infigratinib will stand out. As a scientist, I obviously hope for the most effective product to prevail, and I think we have shown and will continue to show superior effectiveness. This is because our treatment targets the condition at its source, addressing essential signaling pathways. It has outperformed in all preclinical and animal models, as well as Phase II data. It’s the only product that shows a proportional impact, and I believe it will have a wider positive effect on the community we serve compared to CMP products. We don’t observe hypotensive results and I anticipate that our product will have better safety than CNP products. I suspect grade 1 hyperphosphatemia could be around 15 to 20 percent, but this is not as concerning to the market as it may seem. What people really focus on are concerns linked to hypergrowth and spinal issues, and we see no signs of safety problems in those areas. Overall, I believe this drug will prove to be more effective, safer, and more convenient to use, which will help us expand our market, especially as it has been somewhat stagnant lately due to the current drugs. We aim to meet unmet needs and regardless of the specifics, we will have a strong offering for the community.

Operator, Operator

Our next question will come from the line of Jason Zemansky with Bank of America.

Jason Zemansky, Analyst

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?

Neil Kumar, CEO

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.

Operator, Operator

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

Kyuwon Choi, Analyst

Congratulations on the positive news this week. I would like to keep discussing achondroplasia, Neil. As you know, three-quarters of the sales from the currently approved product are coming from outside the U.S., with only a quarter from the U.S. market. Could you share your thoughts on what could contribute to market expansion specifically in the U.S.? You've mentioned the total addressable market, but what are the key factors for expansion in this area? Additionally, regarding the product, how significant do you believe the hypochondroplasia opportunity could be for your infigratinib sales?

Neil Kumar, CEO

Thank you, Paul. I hesitate to discuss the commercial strategies or performance of our competitor. The unmet needs in the physician community and among those affected by achondroplasia are quite similar in both Europe and the United States. Therefore, I believe a solid therapy can succeed in both markets. I expect the usual drug product sales ratio to apply in this category as well. The reason for our competitor's less successful launch could be related to the challenges associated with injectables. We often hear about needle phobia, especially in the U.S., which is something we are more familiar with as a U.S.-based company. We have many conversations with people here, and I think there is indeed a noticeable amount of needle phobia. I can't speak to how they have structured their targeting and sales force, but in Europe, there are generally centers of excellence that cater to a larger portion of the population in any given area. This makes it easier to determine whom to approach and when. This dynamic could contribute to a slower ramp-up for them in the U.S. However, I emphasize again the treatable population for both hypochon and achon. Even with conservative estimates, this represents a significant unmet need that correlates to a reasonably large total addressable market.

Operator, Operator

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

Unknown Analyst, Analyst

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.

Neil Kumar, CEO

Yes, this is indeed a serious issue related to treatment-emergent adverse events, particularly concerning hypercalcemia. This condition involves elevated calcium levels in the blood, which was notably high in the standard of care since it involves calcium intake. Such occurrences are not uncommon and can be managed through titration. In this instance, a patient needed hospitalization for IV fluids to lower their blood calcium levels. However, with the encaleret treatment, the incidence of hypercalcemia was much milder. Although the patient experienced altered mental status and a urinary tract infection, these were unrelated to the drug. They were treated without discontinuation of the drug. Importantly, we observed fewer discontinuations with the drug compared to the standard of care, suggesting that it is safer. Furthermore, we achieved a 76% normalization rate compared to less than 5% with the standard care, which is quite significant. This effectiveness is largely due to the drug’s allosteric mechanism that specifically targets the calcium-sensing receptor, similar to how other targeted treatments work, minimizing the risk of significant side effects.

Operator, Operator

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

Trevor Allred, Analyst

Congratulations on the quarter. I'd like to follow up on encaleret. Can you share more about what gives you confidence that encaleret will exceed $1 billion in sales? Also, could you discuss your expectations for the potential growth opportunity in chronic hypopara?

Neil Kumar, CEO

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?

Trevor Allred, Analyst

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

Neil Kumar, CEO

So less than Yorvipath?

Trevor Allred, Analyst

Yes.

Neil Kumar, CEO

Why?

Trevor Allred, Analyst

I mean it could be more than that...

Neil Kumar, CEO

That's significantly more than the population size. Regardless, that figure is quite low. I haven't come across that before. To put it into perspective for a typical rare disease context, considering figures around $300,000 to $500,000, you're looking at a few thousand patients needing the drug to reach the numbers you mentioned. We always begin with prevalence, which is indeed higher than the identified population. The situation has evolved over the past five or six years, with many claiming that most genetic diseases are substantial in size. Remember, this isn't one of the conditions that drastically shortens lifespan. For those serious conditions, the numbers tend to be inflated because many of those affected don't usually have children, given that most mutations are germline and the populations are quite restricted. The same applies to Canavan disease, which we also research; it doesn't lead to a large patient group. It's simply not supported by epidemiological data. This situation is quite different, featuring a substantial patient base, primarily germline. Even without treatment, patients can still have children. There are several studies indicating a prevalence of up to 12,000 in the U.S. That figure won't be off by much; with only about 1,000 classified under the ICD-10 code and 3,500 already identified. Identifying patients should be manageable through the nonsurgical hypopara community and genetic testing, which I believe will help us enroll a few thousand individuals for this drug. Importantly, guidelines are already established for genetic testing for nonsurgical hypopara patients. Therefore, it is essential for us to promote this within the community. While I don't expect an immediate launch because we have to educate and persuade physicians to incorporate genetic testing into their protocols, we know that even in cases like BRCA or targeted cancer therapies, testing rates in the community can be as low as 40 percent. So, our focus needs to be on collaborating with the appropriate providers and ensuring the search for ADH1 is thorough. Lastly, I am optimistic about identifying these patients and getting them on the drug because of its efficacy. With under 5 percent response rates seen with standard treatments, we're addressing a condition with lifelong challenges such as fatigue, brain fog, and seizures. Many in the rare disease community may think that unless the disease is life-threatening, it is not serious. However, this condition is significantly more debilitating than everyday issues like acne or hair loss. The drug's 76 percent response rate and potential for full normalization approach a therapeutic cure for many patients. This impressive outcome is likely to foster excitement among physicians and patients alike, facilitating our ability to locate a reasonable number of these individuals.

Operator, Operator

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

Chinmay Shukla, Senior Vice President of Strategic Finance

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 three months. Thank you.

Operator, Operator

This will conclude today's call. Thank you all for joining. You may now disconnect.