BridgeBio Pharma, Inc. — Call Transcript 2026

Good afternoon. I'll be your conference operator today. All lines have been placed on mute to prevent any background noise. After the company's remarks, there will be a question and answer session. If you would like to ask a question, press star followed by one on your telephone keypad. If you'd like to withdraw your question, press the pound key. Thank you. Before we begin, I'd 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. 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 fourth quarter 2025 earnings call. My name is Chinmay Shukla. I'm the 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 review our continued strong commercial execution in Attruby's fourth quarter and first full year on the market. More importantly, we will discuss what we believe is a transformative inflection point for BridgeBio, marked by positive top-line phase III results for encaleret in ADH1, BBP-418 in LGMD2I, as well as positive top-line data for infigratinib in achondroplasia. With three successful late-stage readouts across our pipeline, we are entering a new phase of value creation and portfolio maturation. We will also review our robust financial position and how it supports our regulatory launch and lifecycle expansion priorities across these programs. Following our prepared remarks, we will open the call for questions. For the Q&A 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. Thanks, everyone, for taking the time today. This is our first earnings call since we reported the results of our phase III study with infigratinib, which delivered a successful outcome for the community we serve in achondroplasia. Altogether, with ATTR cardiomyopathy, this brings us to four large post-phase III programs. I want to begin my comments today by discussing what that portends in terms of the shape of the firm. In short order, this company will turn from a cash-consumptive business to one that generates significant cash flows. The shape of those cash flows connects to the clinical profiles that we will spend some time discussing today. Before I get into that, though, I want to take a moment to paint the picture of what the overall economic productivity of our post-phase III pipeline might look like over the coming 24 months. I do so because the immediacy of the transition from a cash-losing business to a cash-flowing business is one that happens quickly and can open up new opportunities for a firm as successful at R&D as ours. Last year, we used $446 million for the year net of revenue. Cash burn declined in the fourth quarter relative to the third quarter and throughout 2025, driven by rising revenues and improving operating leverage. While we are going to make significant investments for launch readiness against our next three products, we expect cash burn to roughly hold steady through this year and start declining by the end of next year, given expected increases in Attruby revenue. That's less interesting to me, though, than the following fact: absent any strategic moves, our current pipeline will begin to generate cash in late 2027 and will be a cash generation engine by 2028. The profile we anticipate having in 2028 would distinguish us in a field of genetic disease and more broadly, would place us in the top 20 to 30 firms in the biopharmaceutical sector from the perspective of cash flow or EBITDA. This projected future is driven by growing and diversified revenue streams connected to our four post-phase III assets, which we believe in 2028 will generate more than $600 million in profit. The value of any firm relates back to ROIC, revenue growth, and cost of capital, and against all three metrics, we believe this firm has a rapidly improving profile over the next three years. Our anticipated profit is even more impressive when one considers that we've been able to advance programs from the preclinical stage through phase III at under $300 million, in some cases, considerably under that, and at higher probability of technical success than industry average, suggesting an engine that could drive repeatable organic growth. Of course, all of this now highly probable growth is underpinned by clinical data that we have already generated across our four phase IIIs, as well as data that we continue to generate, and a commercial engine that continues to grow and grow share in the ATTR cardiomyopathy marketplace. We intend to establish that commercial engine as best-in-class for both first-to-market and competitive market launches in genetic disease. Despite continued strong execution across our business, our recent share price performance does not reflect the progress we've made. We believe this disconnect is primarily driven by uncertainty surrounding the tafamidis IP situation, which I will address directly in a moment. Importantly, nothing about our fundamentals has deteriorated. If anything, our position is strengthened commercially, clinically, and strategically. As we execute against our milestones, we believe the intrinsic value of BridgeBio continues to increase. We are keenly aware of the gap between intrinsic value and our current market valuation, and we are actively evaluating all appropriate options to ensure that shareholder value is properly recognized over time. More specifically, over the past three months, given the de-risking of LGMD2I, our patient finding progress in ADH1, and the clearly differentiated infigratinib read out in achondroplasia, we believe our intrinsic value has increased and its error bars have narrowed. With over $1 billion of capital on our balance sheet and additional significant amounts of capital available away from the equity markets, and with the base business fully financed, we believe we have retained optionality to capture the value you all have helped us to create. With that said, I want to spend some time today reiterating some of the important clinical data, especially as it pertains to the infigratinib read out. I want to highlight ongoing commercial readiness activities for LGMD2I and ADH1, and I want to talk about, and Matt will elaborate on this, our continued commercial progress in ATTR cardiomyopathy. On the data side, I'll begin with our recent phase III readout in achondroplasia. As many of you know, we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile for infigratinib. The study successfully met the primary endpoint of change from baseline in average height velocity at week 52, with a p-value of less than 0.0001, with a mean treatment difference against placebo of 2.1 cm per year. In key secondary endpoints, infigratinib also demonstrated the first statistically significant improvement in body proportionality in achondroplasia, with a least squares mean difference of -0.05, with a p-value of less than 0.05 against placebo in children younger than eight years old, which were more than 50% of our participants, and in a pre-specified analysis. It succeeded on change from baseline in height Z-score at week 52, with a least squares mean increase on the treatment arm of 0.41 standard deviations at week 52, associated with a p-value of less than 0.0001. All of these numbers, as a reminder, are best-in-class and unique to infigratinib. Infigratinib was also well-tolerated, with no discontinuations or serious adverse events related to study drug. Three cases or 4% on active of hyperphosphatemia, considered a mild and transient, with no cases requiring either dose reduction or discontinuation, and no adverse events associated with the inhibition of FGFR1 or 2, for example, retinal or corneal adverse events. A reminder, infigratinib's differentiated oral route of administration and its mechanism, which uniquely targets this well-described condition at its source, produced phase II efficacy and safety results that were highly differentiated. Our phase III data have confirmed those efficacy and safety profiles. Interestingly, as we have begun to test this product profile since the readout, we have heartily found that our base case achievable market share has risen from the 52% I mentioned in my JPMorgan talk to an excess of 65% peak year share. In addition, that preliminary market research suggests not only differentiated peak year share, but also significant market expansion, similar to what we've seen when orals enter markets as diverse as Fabry, migraine, hereditary angioedema, and in many other categories. In fact, a recent analysis done at our Revenue Institute in partnership with MIT suggests that across indications, the launch of an oral product increased the sales in the category by about 170% over five years from launch of the first oral product. With regards to our efforts in LGMD2I, we're excited to be presenting the full data set from our study at the upcoming Muscular Dystrophy Association Conference, where Dr. Katherine Mathews from the University of Iowa will give the keynote. We have built and onboarded a dedicated commercial leadership team to ensure we are fully prepared to serve the LGMD2I community from day one. This is a population with profound unmet need, and we are ready to execute. At the same time, we are not limiting our focus to the patients already identified. We are actively working to expand awareness, accelerate diagnosis, and help uncover individuals who may be unidentified within the broader LGMD or Becker muscular dystrophy populations. Our goal is simple: to find every patient who can benefit and to ensure we are ready to reach them the moment we are able to. Moving to ADH1, our other first-in-class product, encaleret, we continue our patient-finding efforts, which have already identified in excess of 1,700 unique patients in claims data. We also recently had pre-NDA communications with the agency, which were supportive of our expectations, and we continue to anticipate the launch of both encaleret and BBP-418 in late 2026 or early 2027. Finally, and most importantly, I want to talk about our ATTR cardiomyopathy franchise, where, as I suggested recently, we continue to elaborate not only on the fullness of the best-in-class stabilizer hypothesis, but also on our differentiation in the real-world setting and our ability to impact patient health as early as one month. By far, the earliest impact we see from any medicine in this space. We already pre-announced the fourth quarter Attruby net product revenue of $146 million, which corresponded to greater than 25% MBRX share as of December 31st, 2025. Over the last few weeks, Attruby's commercial momentum has continued. As of February 20th, we have seen 7,804 unique patient prescriptions written by 1,856 unique prescribers. You'll hear more from Matt about what this means in terms of competitive differentiation, and as I alluded to as well in my JPM talk, we are continuing to interrogate the importance of the cardiorenal axis, which seems to be uniquely involved in our early onset of action. We have also noted with great interest the recent PNAS paper, that I only had a bit of time to talk about at JPMorgan, which suggests that binding enthalpy best predicts the conformational stabilization imparted by kinetic stabilizers, as opposed to binding affinity, KD or Gibbs free energy. As we have shown through ITC experiments and as we published in Miller et al., we have a vastly superior enthalpic binding mode than does tafamidis, which, in concert with superior binding kinetics, continues to reinforce Attruby's better stabilization profile. A recent bevy of literature further supports that increases in serum TTR are associated reliably with decreases in the relative risk of mortality. These papers suggest that for every mg per dL increase in serum TTR, you decrease the risk of mortality at 30 months by approximately 5%. As a reminder, we observed in our phase III study that patients increased their serum TTR by 3 mgs/dL when moving from tafamidis to acoramidis. This suggests a whopping 15% relative risk reduction in mortality when moving from tafamidis to acoramidis. Let me also address the recent stock volatility, which is largely centered on questions regarding Vyndamax IP and the potential for generic entry. It's important to separate two things: the legal process around tafamidis and the fundamental strength of Attruby. Our confidence in Attruby is rooted in its clinical profile and market positioning, not a particular IP outcome. On the IP front, the Pfizer decision to withdraw one of its EU patents defending the Vyndamax equivalent product was unexpected. That said, it did not materially change how we view the EU market, given Vyndamax's Orphan Drug Exclusivity in wild-type ATTR cardiomyopathy through 2030, which is now and how we have always consistently modeled that geography. In the U.S., which is the market of greatest importance to us, we believe the IP position is stronger. The patent claims at issue are narrower than those in Europe, including specific XRPD peak limitations for Form 1 that were not part of the EU case. In addition, U.S. law applies a higher legal threshold for invalidity, requiring that challengers prove by clear and convincing evidence that a prior art process necessarily and inevitably produces the claimed form, not merely that it could or likely would. That said, IP trials are inherently uncertain, and we will reassess as more information comes available following the U.S. proceedings in April. Stepping back, however, our strategy does not depend on tafamidis IP. Attruby has demonstrated near complete stabilization, rapid clinical benefit, and meaningful differentiation in ATTR cardiomyopathy. It is already priced at a discount to Vyndamax and is less than half the price of the knockdown technologies. We believe physicians are making decisions based on clinical performance, not simply price, and prescribing trends we are seeing are reflecting that. Even in a hypothetical scenario involving generic tafamidis, we do not believe a less efficacious product would undermine the role of a clinically differentiated therapy in a serious progressive disease like ATTR-CM. In short, we remain confident in Attruby's positioning today and in the years ahead. With that, I'll turn it over to Matt to speak more specifically about the commercial momentum we're seeing. Thank you, Neil. Consistent with what we highlighted at JPMorgan in January, we believe 2025 reflected strong commercial momentum for Attruby, and it represented an important step forward in advancing three additional product candidates towards potential commercialization. In the fourth quarter, we delivered 35% quarter-over-quarter growth in net product revenue, ending the year with $502.1 million in total revenue and $154.2 million in quarter four. Of this, the net product revenue for Attruby was $362.4 million and $146 million, respectively, while new patient growth accelerated in the latest quarter to reach 7,804 new patient starts. When viewed in conjunction with the IQVIA data, it becomes clear that Attruby is accelerating growth at a significantly faster rate versus previous quarters, while the competition lags behind. This is particularly obvious in first-line patients, where the exceptional data for Attruby, along with our experienced field teams, have driven sales to the highest levels since launch, surpassing all expectations. We have historically given out the new patient start number each quarter and have done so again, despite the competition not offering similar numbers. Moving forward, we will not be offering new patient start data because of this lack of transparency by others. Continuing to do so would put us in a competitive disadvantage, but our expectations are that Attruby will continue to grow as it has done since launch and as exemplified with today's update. As adoption grows, particularly in the first-line setting, we remain focused on ensuring patients and healthcare professionals have clear, balanced information when evaluating therapy options. That focus is especially relevant given recent updates we've seen in competitor direct-to-consumer communications. After receiving a letter from the FDA several months ago and pulling their television ad from the airwaves, Alnylam has returned to TV advertising, but of note, the safety section has been updated. Besides adding the warning about the risk of eplontersen lowering vitamin A and potentially affecting vision, the ad now points out the risk for several additional concerns, namely joint pain, pain in the arms and legs, and shortness of breath. In a population already often suffering from these issues, the possibilities of amplifying, compounding, or causing shortness of breath and/or pain in the joints and/or pain in the arms and/or pain in the legs should be highlighted to any patient considering treatment with eplontersen. The fact that these risks had been omitted but are now stated at the end of each commercial, and hopefully all promotional materials and messaging, will correct and highlight for patients and healthcare professionals some things to consider with eplontersen treatment, especially if they are a newly diagnosed patient versus someone who has tried all other options. If we shift back to the reasons for the growth of Attruby, there are several driving factors. First, the number of prescribing HCPs continues to grow, but of equal importance, HCPs who start using Attruby continue using Attruby. We are seeing repeat use and stable patient persistence, which tells us physicians are comfortable with what they are seeing in their practice. We believe the success we have seen in 2025 is driven by Attruby's differentiated profile as the only near-complete stabilizer on the market, in contrast to therapies that rely on partial stabilization or partial knockdown mechanisms of action. Attruby has also demonstrated the fastest time to separation to date, an attribute that matters as physicians seek therapies that can deliver meaningful benefit quickly. Importantly, persistency and adherence for Attruby continue to exceed our original expectations, which were based on historical ATTR treatment patterns, reinforcing our confidence in the durability of the franchise. We believe we have the strongest commercial teams in the industry, spanning sales, marketing, strategy, analytics, and market access. Many team members have worked together for years. We've continued to build on that foundation with targeted hiring of top talent, including the recent expansion of the Atrusi sales team. Overall, Q4 reflects continued progress across key metrics, including growth in patients on therapy and ongoing use by prescribers. We are excited to see continued growth in quarter one as we head into 2026. Turning to the pipeline, we are focused on the next wave of potential launches. We are excited by the recent clinical results for BBP-418, encaleret, and infigratinib, all of which exceeded expectations across their primary and secondary endpoints. Based on the strength of these data, we believe each program will be the leader in its respective market and bring much-needed therapies to families and patients in need of care. Building on the successful launch of Attruby, we have established a proven commercial foundation and are well-positioned to extend this model as we prepare for future launches across our pipeline. We look forward to going into more detail as we get closer to approval for each. I will now turn the call over to Tom. Thank you, Matt, and good afternoon, everyone. I'll now discuss our financial results for the fourth quarter and full year of 2025. Please note that our commentary on today's call will focus on GAAP financials, unless otherwise indicated. Total revenues were $154.2 million in 4Q 2025, consisting of $146 million of Attruby net product revenue, $5.3 million of royalty revenue, and $2.9 million of license and service revenue, compared to total revenues of $5.9 million for the same period last year. The $148.3 million increase in total revenues was primarily driven by a $143.1 million increase in net product revenue from Attruby, reflecting broad-based growth across market segments, including accelerating first-line adoption, increasing new patient starts, expanding prescriber depth, and strong persistency and adherence, supporting durable revenue growth. We also recorded an increase of $5.1 million in royalty revenue from ex U.S. net sales of Beyonttra in Europe and Japan. For the full year 2025, total revenues were $502.1 million, compared to $221.9 million for the full year 2024. The $280.2 million increase in total revenues for the full year was primarily due to $359.5 million increase in net product revenue from Attruby and an $11.2 million increase in royalty revenue from sales of Beyonttra, partially offset by a $90.5 million decrease in license and service revenues versus the prior year. Total operating costs and expenses for the fourth quarter of 2025 were $293.7 million, compared to $231.9 million in the same period in the prior year. The $61.8 million increase in operating costs and expenses was primarily driven by a $63.3 million increase in SG&A expenses, partially offset by a $13.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. For the full year 2025, total operating costs and expenses were $1 billion, compared to $814.9 million in the prior year. The $210.6 million increase was primarily driven by a $242.3 million increase in SG&A, largely reflecting the company's investments to support the commercial launch and ongoing activities for Attruby. This increase was partially offset by a $54.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. Turning to our balance sheet, we ended the year with a cash position of $587.5 million in cash equivalents, and marketable securities. We completed the issuance of $632.5 million aggregate principal amount of 2033 convertible notes in January 2026, which provides significant cash runway to continue supporting our transition into a diversified, late-stage, multi-product business. 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. Thank you. At this time, I'd like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We'll pause for just a brief moment to compile the Q&A roster. Your first question comes from the line of Salim Syed from Mizuho. Your line is live. Hi, guys. This is Bennett for Salim. Thanks for taking our question. Congrats on another quarter of continued patient growth. If I may, could you comment on why Attruby continues to show consistent growth even as competitors' growth seem to be slowing down? I mean, can you comment on what are the key drivers behind it, what is the feedback that you feel is resonating more with docs and patients now that we are several quarters in? Thank you. Thanks, Bennett. Maybe I'll turn it to, Matt to answer that question. Sure. Thanks. I think it's multifaceted, but a big part is the field team that we have at BridgeBio. The right team makes or breaks a launch, and that's across both commercial and medical. Of course, there's the data. No one's been able to show better data or near complete stabilization, only Attruby. I think the time to separation is a big factor, and you heard some of that in the earlier comments. I think finally, we've stayed disciplined and focused on what's important for patients and HCPs. We have category-leading efficacy and safety with consistent results across all patient types. A great team and a great medicine, I think it's hard to slow down. Maybe I'll just build on that. You can, you can see in the new patient script number something kind of interesting where we had that rapid acceleration at first, sort of plateaued, and now we have a second wave of acceleration. That's sort of rare if you look and model most launches, where you see kind of a burst of activity and then, and then typically you see a slowing. That really portends one of two things. One is obviously rapid patient identification, which I think we are seeing in the field. Secondly, it's really a second wave of prescribers that are starting to wake up to some of the messages that we're putting forth. That, I think, is an exciting profile generally for a launch this early in. You know, couple that with nearly 1,200 new scripts since I gave my JPM talk, that's a very, very exciting trajectory right now. All right. Thank you. Your next question comes from the line of Mani Foroohar from Leerink Partners. Your line is live. Hey, thanks, guys. Congrats on continuing to show volume growth in the face of competitors who are seeing slowdowns. You've talked a lot about the commercial differentiation and differences in your growth trajectory versus competitors. Lots of different pieces of data go into that. I want to look past out into just what the timeline is into whenever tafamidis gets generic and beyond, about clinical differentiation, which you've identified as core to your strategy to driving continued growth and durability in the face of a generic whenever that happens. Can you tell us when we'll have significant incremental real-world data, longer-term data from acoramidis to establish that difference in clinical benefit that you guys are hanging that growth tail on? Yeah. Great question, Mani. Thanks for it. you know, I think first, the key is for us to really start to get some of the data that we presented in the last year out into the field and understood. Maybe just a couple pieces that I think have been overlooked or are just starting to really make their way into the field. First and foremost is the early impact, that impact as early as one month that I talked about at JPM. We continue to interrogate the precise mechanism behind it. As you know from these clinical trials and a lot of the real-world evidence, early CVH is extremely common. You want to get patients on the drug that can take action as early as possible. Not only for that reason, obviously this is an ongoing mass action and deleterious disease, so you wanna be on the drug that has the earliest impact. The second is, the AF data that we put forth. You know, nearly 60% of patients in this space suffer from AF or cardiac arrhythmic events. I think the most important piece of the data that we put forth when we showed the 17% reduction, as published last year, is that we're having an equivalent effect on or off in AF, in the AF subpopulation. So, you know, when you think about AF patients being slightly harder to manage in the context of ATTR cardiomyopathy, here you have a drug that has consistent and high impact. In fact, the highest point estimate we've seen in terms of both reduction in downstream outcomes of 43% and reduction in AF itself of 17%. That I think, is the second piece that we need to do a better job of educating on, and I think physicians will find it exciting. Finally, it's the variant population, right? The sickest by far, of the subpopulations. They do deserve a better drug, and that 0.41 hazard ratio that we presented on with statistical significance, even more impressive given the fact that less than 10% of our patients on Attruby were a variant patients. I think that is the best point estimate, again, with the best statistical significance in the space, and extremely consistent with the binding mode that we've articulated, which is differentiated against tafamidis. Those would be, I think, the things that we need to do a better job of driving into the marketplace right now. On a go-forward basis, the two big areas that we're interrogating, number one, are real-world evidence, which you should see by the end of this year, this calendar year. The second is the cardiorenal axis work that we're doing, where we think we have a unique signal that connects, interestingly, to the early onset of activity and could really, I think, change the shape of this marketplace going forward. That's what I'd say on that front. I have a quick follow-up, more on firm-wide strategy. You guys have talked about the transition towards cash flow generation over the course of a couple of years. Obviously, that happens when you have multiple high-margin, small molecule assets. Can you talk about how you guys think strategically long term about use of cash and where and how to put that incremental free cash flow to work? I'm not saying call for a dividend buyback, et cetera, BD, but just how you guys think about your strategy and where that capital should go in a 2028, 2029, 2030, et cetera, free cash flow generating BridgeBio? Totally. Well, I would say at the very highest level, as we've been talking about, I think a little bit more over the last couple of months, we're very pleased with the efficiency of our R&D engine. Efficiency, both in terms of time and cost and obviously, the validity of it as it pertains to probably a technical success. As we talked a little bit about, you know, a few months ago, Manny, I know you and I have connected on this. The pipeline that is attended at Gondola is a wonderful example of the ample substrate available to help patients with genetic disease, and our objective function is to serve as broadly as possible. Given all of those things, with cash flow, we would intend, as long as we can beat our cost of capital, to continue to reinvest into R&D and in some cases bring in partially owned assets that we have access to, through Gondola and bring those forward into the, again, highly efficient operating model that we've established in mid to late stage development and ultimately in the, in the commercial setting. Obviously, you know, the stock's not trading where we would like it to trade, and it's trading quite a, quite a ways off intrinsic value. There are opportunities to do other things with cash flows, namely share buybacks and dividends, if indeed, we don't feel we can capture the NPV of fully financed assets, as they move into the marketplace. A bit of this will be just to see whether or not we can do a better job of helping investors avail of the value that we create, and getting the stock price and cost of capital back up into a normal realm. That, I hope, would, you know, sort of get us going in terms of growth in the R&D, in the R&D sector. Does that answer your question? Thank you. Absolutely. Congrats again on a good quarter. Thanks, Mani. Your next question comes from the line of Tyler Van Buren from TD Cowen. Your line is live. Hey, guys, thanks for taking the question. Following the three successful phase III in recent months, can you elaborate on your launch readiness and expected field footprint in the context of your burn commentary and the expected cadence of regulatory and commercial catalysts over the next 12 to 18 months? Yeah, thanks, Tyler. Maybe I'll ask Matt and Tom to comment on that. Sure. Hey, Tyler. I think, you know, we're going to follow the same rigor as what we did for the Attruby launch. I think one of the big differences is this time we'll be launching on a global basis, and as a part of that, we're building in the U.S., but also ex-U.S. as well. We'll have more on that towards the end of the year in terms of both additional revenue for Attruby that will be coming rest of world, but also our prep and build out for the three additional launches in the U.S. and the rest of the geographies as well. I think what's important, you've seen the recent data readouts. We're setting or resetting the standard of care for each and everyone. For LGMD2I and ADH1, it's going to be a first and best-in-class story, and for achon, it's going to be resetting the standard with best-in-class data. I'll take the question on burn. As we've discussed, we've seen over the last several quarters, our cash burn has been on a downward trajectory. That's driven first and foremost by the strong ramp of Attruby and gross profit that it provides. I would also say that it's been due to our disciplined OpEx profile here. As we look to ramp the next three launches, we do expect a gradual increase in OpEx throughout the year. However, we expect burn to hold steady throughout most of the year and drop off again towards the end of the year, as we continue to see an expanding operating margin provided by the Attruby brand. Thanks for the question, Tyler. Your next question comes from the line of Biren Amin from Piper Sandler. Your line is live. Hey, hi, guys. Thanks for taking my questions, and congrats on the quarter. I have a high-level question. As you've demonstrated impressive productivity and outlined The BridgeBio Way as a sustainable development model, which was highlighted in the Drug Discovery Today manuscript recently in January. With that in mind, and as we look, you know, beyond 2025, what are the key drivers of momentum for the company, and when should investors expect new assets out of the pipeline? Thank you. Yeah, thanks, Biren. Thanks for the question. you know, a little bit overlapping with some of my comments that I gave against Mani's question as well. Maybe I'll just say, like, near term, our focus continues to be obviously, making sure that these drug products that we just registered successful Phase III on, are approved and ultimately launched correctly. That's the highest and best use of our time right now. The second best use of our time are the additional indications associated with medicines that we know are safe and effective, such as obviously chronic hypopara in the context of encaleret and hypochon and some of the other height disorders that Justin has talked about in the past, associated with infigratinib. Those, that'd be the sort of second category of growth. I think you're asking the right question. Look, at the end of the day, as I mentioned earlier, the scientific substrate available to us to target well-described genetic conditions at their source continues to grow, and we're finding starting points all the way from the clinic, back to, you know, early stage discovery, where we're probably most adept. And that's highlighted in the ever-growing pipeline at Gondola, which obviously BridgeBio shareholders partially own. I would think over the course of time, if indeed we're able to correct our cost of capital and trade closer to intrinsic value, number one, and number two, we're able to really stick the landing and effectively get these drugs approved and launched. There will be a moment where we can bring some of those other assets in and prosecute them with the great infrastructure that we've already set up here, namely, you know, mid- and late-stage development, regulatory, the ability to put it in the hands of a great commercial team, and to do all of that efficiently in terms of time and cost. That, that's kind of the high level answer, I don't have anything specific on a specific asset that we would bring in and like that. I do think you should look for us generally to rely on organic, not inorganic growth. Organic meaning from the ecosystem of BridgeBio activities and BridgeBio companies, and not looking for big M&A or anything like that. We tend to look at that as a rather expensive mode of growth and one that we probably don't need to take on, given the fact that we're getting to INDs in less than $10 million or $15 million and through Phase I/IIs in less than $100 million. Unless we run out of ideas internally, I don't think we would be aggressively moving toward M&A for growth in the next three to five years. Great. Did I answer your question, Biren? Yep. Perfect, well. Your next question comes from the line of Cory Kasimov from Evercore ISI. Your line is live. Hi, this is Adi on for Cory. I wanted to ask on infigratinib. Now, with the phase III data in hand, how are you thinking about the competitive landscape across not just CNP pathway therapies, but also other FGFR-targeted programs, which are more specific to FGFR3? Thank you. Thanks for the question. Yeah, Justin, you want to take that? Yeah. Yeah, thanks for the question. Really, we believe the balance of efficacy and safety shown in PROPEL 3 prove that infigratinib is not just best-in-class, but potentially last-in-class in achondroplasia. Now, on the efficacy side, we had a +2.1 cm per year change from baseline age three, and the first and only stat sig improvement proportionality. Most importantly, we normalize absolute HV, bringing back kids with achondroplasia to wild-type growth levels of 6 cm per year. You know, across every single measure of efficacy, whether it be in animal models or in a clinic, we have set a new bar here. On the safety data side, we had a home run outcome, right? With basically no change in mean phosphate levels between the placebo and treatment arms, and no signs of FGFR1 or 2 associated toxicity. Really, I think the other molecules being developed in the space, whether it be CNP or FGFR3 inhibitors, have two issues. One, on the efficacy side, you actually don't want to overshoot 6 cm per year too much. We've heard from clinicians that the skeletons and bones in achondroplasia aren't built for too much growth, given preexisting low bone mineral density, and we really hit the sweet spot there. On the safety side, we obviously avoid all the well-known issues associated with the CNP class, such as on vasodilation. Now, the other FGFR3 inhibitors in development trade off selectivity for FGFR1 and 2 for significant VEGFR3 liabilities. There's two issues related to that, and they're not just theoretical risk. The first is on spermatogenesis, and because of this, enrollment in trials are restricted to prepubertal males for these other programs. The second, and potentially even more overlooked issue, is the effect on angiogenesis. Many molecules that have in-vitro potency findings for VEGFR3, even without clinical findings, end up with a box warning on their labels for impaired wound healing. A great example of this is Retevmo. Net-net, we're really happy with where we've landed on data, and our safety profile obviates the need for other FGFR3 inhibitors. We absolutely could go further in dose given our safety data, but really think that there's no need to in achondroplasia, given that we have gone back to wild-type levels of growth. I hope that answers your question. Your next question comes from the line of Eliana Merle from Barclays. Your line is live. Hey, guys. Thanks for taking the question. Thanks for all the color so far, but, if you could go over your views, in a little bit more depth on the taf IP, and some color there, and specifically your base case for when tafamidis goes generic in the U.S., how you're thinking about it, and can you elaborate on why this doesn't matter for Attruby, in your view? I have a follow-up question. Thanks. Hey, Ellie, thanks for the question. Yeah, I mean, you know, broadly, we tend not to comment on the IP situation for our competitors, but obviously it's been a big story for the stock here. Let me turn it over to Chinmay to take a crack, and I'm happy to elaborate on it. Yeah, happy to take that. Ellie, thanks for the question. Maybe I'll talk about it in two ways. I think, as Neil mentioned, we try not to talk about our competitor's IP, especially when the competitor is, you know, not as, we believe, not as potent as our molecule. I think let's talk a little bit about what we think will happen on the trial and maybe a little bit on our strategy for why this doesn't really matter. I think maybe I'll start quickly on Europe, since I know you had some questions there. I think it's important to note that Pfizer, you know, withdrew its patent there, and so that's going to limit the precedential value of this ruling for related parties in other jurisdictions. I think as Neil highlighted in his prepared remarks, our base case for Europe has always been entry and, you know, generic entry in 2030 and, you know, that's based on ODE for wild-type ATTR-CM. That's still our assumption. There are two more patents in Europe which protect Pfizer, so there may be some potential upside there. It's also important to note on that front, the really strong treatment, [naive] share that [Brian] has been achieving, you know, which talks a little bit about how physicians, not just in the U.S., but globally, are recognizing the differentiation of acoramidis. Turning to the U.S., which I think is the market, which probably matters a little more, I think Neil had a bunch of comments in his prepared remarks, on how we think about it. Based on publicly available information, I think that a couple of things are interesting to note there in addition to what Neil said. One is that Dexcel, which is, I think, the lead filer, has conceded infringement of the 441 polymorph patent. The other interesting thing to note is also that the bar for validity is much more innovator-friendly under U.S. law. As Neil mentioned in his remarks, you know, IP is always uncertain, so we'll keep monitoring it and seeing what happens in Europe in April in the U.S. trials. I think that we feel good about where we are right now, and I think that we do feel like Vyndamax should have protection into the 2030s, potentially up to 2035. I think it's important to note, though, that we feel like the tafamidis IP debate is a little bit of a sideshow. It doesn't really matter for Attruby's uptake. you know, you guys heard today from Neil and Matt and everyone else about the tremendous momentum which we are seeing for Attruby. You know, the patient weeks, number of patients per week continues to increase as we go forward in our launch and continues to accelerate. I think that's driven by the differentiated clinical data which we have for Attruby. Even in a scenario where a generic tafamidis enters the market, we just don't believe that a less efficacious product will displace a clinically superior therapy in a serious progressive disease. We've seen this pattern, by the way, play out in multiple therapeutic areas such as PH, statins, prostate cancer, where differentiated second to market molecules continue to grow even after the first to market post-generics. We feel good about the long-term value of Attruby, and I think that we look forward to continuing to execute against that. Great. Thanks so much. Just a quick follow-up. How do you see the use of serum TTR in clinical practice in the real world evolving and your perspective there, and how that could potentially show differentiation for physicians? Thanks. Yeah, great question, Ellie. I'd say first and foremost, you probably saw the recent two JACC papers that came out, you know, looking at serum TTR elevation and correlating it with downstream relative risk of mortality reduction. Both of those were associated with tafamidis, but they reiterated the point that our publication last year made, which is that ever higher levels of serum TTR are associated with ever lower levels of downstream mortality, and that roughly, you could imagine every 1 mg/dL increase, leading to about a 5% relative risk reduction, in downstream mortality. That's exciting. Obviously, the studies that Pfizer did had significantly higher levels of variant patients in them. You're going to see a similar serum TTR rise as you saw in our studies, but that's just basically rigged up so that you can see a higher increase because you've got many more variant patients. If you normalize for variant to wild-type patients, even in cross-trial studies or cross-study comparisons, you can see that we have a significantly higher serum TTR elevation. I think that the most interesting data from that standpoint were literally the same patients going from tafamidis on to acoramidis in the context of our OLE and ATTRibute, where you saw, as I mentioned earlier, that 3 mg/dL increase when going from a partial stabilizer to a full stabilizer. I think now we can say, and I remember, Ellie, having this debate with you a long time ago, even just like, what is the shape of that response curve in terms of ever higher levels of stabilization, leading to ever better outcomes? I think here at least we can say it's roughly 5% per mg/dL. You know, it's about a 15% relative risk reduction in terms of mortality going from taf to acoramidis, putting aside the earlier onset of action and some of the other advantages. I think serum TTR will become ever more important, based on these, this bevy of publications. Let's see, it's not, it's not broadly used. I don't know, Matt, if you disagree right now, but I think, you know, our hope is on a go-forward basis, it'll become an ever more important marker of drug action and also therapeutic choice. Great. Thanks for the color. Yeah. Thanks, Ellie, for the question. Your next question comes from the line of Andrew Tsai from Jefferies. Your line is live. Hey, good afternoon. Thanks for taking my question. Just wanted to stick on the theme of cash burn and near-term profitability. What are your guidance expectation on Priority Review Vouchers for non-dilutive capital? I think they're going for $200 million and $300 million apiece right now. Which of your pipeline drugs, or even which indication per drug, could be eligible for PRVs, and when do you expect to receive them? Thank you. Yeah, good question. I didn't factor that into my earlier comments, but, Tom, you want to take that? Yeah, sure, I'll take that. First, absolutely thrilled to see that program has been reauthorized. It's been a hugely successful incentive for BridgeBio and companies like us in being able to responsibly invest in diseases that affect very few patients and otherwise would be at risk of being left behind. Really happy that that's been extended. We actually have three programs that have already received Rare Pediatric Disease Designation and we expect to be eligible to receive a PRV upon approval. Those are 418 for limb-girdle, infigratinib for achondroplasia, our Canavan gene therapy program. As you rightly pointed out, the pricing of these is not only held in but risen over the last few months. There's significant asset value there already within our portfolio. Looking out more broadly to the Bridge ecosystem, many of the programs we work on over at Gondola Bio affect children. I would expect there to be many more PRV-eligible programs in the ecosystem around Bridge. Great day for patients and biotech companies like us that are focused on rare disease communities. Thanks. That concludes our question and answer session for today. I'll now hand it back over to the company. Thank you, investors, for joining us on our call today and for the analysts to ask the questions. We look forward to updating you on our next quarterly call in a few months. Thank you. That concludes today's meeting. You may now disconnect.

Speaker 10: Good afternoon. I'll be your conference operator today. All lines have been placed on mute to prevent any background noise. After the company's remarks, there will be a question and answer session. If you would like to ask a question, press star followed by one on your telephone keypad. If you'd like to withdraw your question, press the pound key. Thank you. Before we begin, I'd 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. Good afternoon. good afternoon I'll be your conference operator today. i'll be your conference operator today All lines have been placed on mute to prevent any background noise. all lines have been placed on mute to prevent any background noise After the company's remarks, there will be a question and answer session. after the company's remarks there will be a question and answer session If you would like to ask a question, press star followed by one on your telephone keypad. if you would like to ask a question press star followed by one on your telephone keypad If you'd like to withdraw your question, press the pound key. if you'd like to withdraw your question press the pound key Thank you. thank you Before we begin, I'd 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. before we begin i'd 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. 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. 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. 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. 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. all statements made here are based on information available to bridgebio as of today The company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. 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. with that completed bridgebio you may begin your conference

Speaker 4: Good afternoon, everyone, and thank you for joining BridgeBio Pharma's fourth quarter 2025 earnings call. My name is Chinmay Shukla. I'm the 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 review our continued strong commercial execution in Attruby's fourth quarter and first full year on the market. More importantly, we will discuss what we believe is a transformative inflection point for BridgeBio, marked by positive top-line phase III results for encaleret in ADH1, BBP-418 in LGMD2I, as well as positive top-line data for infigratinib in achondroplasia. Good afternoon, everyone, and thank you for joining BridgeBio Pharma's fourth quarter 2025 earnings call. good afternoon everyone and thank you for joining bridgebio pharma's fourth quarter 2025 earnings call My name is Chinmay Shukla. my name is chinmay shukla I'm the Senior Vice President of Strategic Finance at BridgeBio. i'm the 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. 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 review our continued strong commercial execution in Attruby's fourth quarter and first full year on the market. during today's call we will review our continued strong commercial execution in attruby's fourth quarter and first full year on the market More importantly, we will discuss what we believe is a transformative inflection point for BridgeBio, marked by positive top-line phase III results for encaleret in ADH1, BBP-418 in LGMD2I, as well as positive top-line data for infigratinib in achondroplasia. more importantly we will discuss what we believe is a transformative inflection point for bridgebio marked by positive top-line phase iii results for encaleret in adh1 bbp-418 in lgmd2i as well as positive top-line data for infigratinib in achondroplasia With three successful late-stage readouts across our pipeline, we are entering a new phase of value creation and portfolio maturation. We will also review our robust financial position and how it supports our regulatory launch and lifecycle expansion priorities across these programs. Following our prepared remarks, we will open the call for questions. For the Q&A 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. With three successful late-stage readouts across our pipeline, we are entering a new phase of value creation and portfolio maturation. with three successful late-stage readouts across our pipeline we are entering a new phase of value creation and portfolio maturation We will also review our robust financial position and how it supports our regulatory launch and lifecycle expansion priorities across these programs. we will also review our robust financial position and how it supports our regulatory launch and lifecycle expansion priorities across these programs Following our prepared remarks, we will open the call for questions. following our prepared remarks we will open the call for questions For the Q&A session, we will also be joined by Ananth Sridhar, Anna Wade, and Justin To, who lead encaleret, BBP-418, and infigratinib, respectively. for the q&a 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. with that i'll turn it over to neil

Speaker 9: Thanks, everyone, for taking the time today. This is our first earnings call since we reported the results of our phase III study with infigratinib, which delivered a successful outcome for the community we serve in achondroplasia. Altogether, with ATTR cardiomyopathy, this brings us to four large post-phase III programs. I want to begin my comments today by discussing what that portends in terms of the shape of the firm. In short order, this company will turn from a cash-consumptive business to one that generates significant cash flows. The shape of those cash flows connects to the clinical profiles that we will spend some time discussing today. Before I get into that, though, I want to take a moment to paint the picture of what the overall economic productivity of our post-phase III pipeline might look like over the coming 24 months. Thanks, everyone, for taking the time today. thanks everyone for taking the time today This is our first earnings call since we reported the results of our phase III study with infigratinib, which delivered a successful outcome for the community we serve in achondroplasia. this is our first earnings call since we reported the results of our phase iii study with infigratinib which delivered a successful outcome for the community we serve in achondroplasia Altogether, with ATTR cardiomyopathy, this brings us to four large post-phase III programs. altogether, with attr cardiomyopathy this brings us to four large post-phase iii programs I want to begin my comments today by discussing what that portends in terms of the shape of the firm. i want to begin my comments today by discussing what that portends in terms of the shape of the firm In short order, this company will turn from a cash-consumptive business to one that generates significant cash flows. in short order this company will turn from a cash-consumptive business to one that generates significant cash flows The shape of those cash flows connects to the clinical profiles that we will spend some time discussing today. the shape of those cash flows connects to the clinical profiles that we will spend some time discussing today Before I get into that, though, I want to take a moment to paint the picture of what the overall economic productivity of our post-phase III pipeline might look like over the coming 24 months. before i get into that though i want to take a moment to paint the picture of what the overall economic productivity of our post-phase iii pipeline might look like over the coming 24 months I do so because the immediacy of the transition from a cash-losing business to a cash-flowing business is one that happens quickly and can open up new opportunities for a firm as successful at R&D as ours. Last year, we used $446 million for the year net of revenue. Cash burn declined in the fourth quarter relative to the third quarter and throughout 2025, driven by rising revenues and improving operating leverage. While we are going to make significant investments for launch readiness against our next three products, we expect cash burn to roughly hold steady through this year and start declining by the end of next year, given expected increases in Attruby revenue. I do so because the immediacy of the transition from a cash-losing business to a cash-flowing business is one that happens quickly and can open up new opportunities for a firm as successful at R&D as ours. i do so because the immediacy of the transition from a cash-losing business to a cash-flowing business is one that happens quickly and can open up new opportunities for a firm as successful at r&d as ours Last year, we used $446 million for the year net of revenue. last year we used $446 million for the year net of revenue Cash burn declined in the fourth quarter relative to the third quarter and throughout 2025, driven by rising revenues and improving operating leverage. cash burn declined in the fourth quarter relative to the third quarter and throughout 2025 driven by rising revenues and improving operating leverage While we are going to make significant investments for launch readiness against our next three products, we expect cash burn to roughly hold steady through this year and start declining by the end of next year, given expected increases in Attruby revenue. while we are going to make significant investments for launch readiness against our next three products we expect cash burn to roughly hold steady through this year and start declining by the end of next year given expected increases in attruby revenue That's less interesting to me, though, than the following fact: absent any strategic moves, our current pipeline will begin to generate cash in late 2027 and will be a cash generation engine by 2028. The profile we anticipate having in 2028 would distinguish us in a field of genetic disease and more broadly, would place us in the top 20 to 30 firms in the biopharmaceutical sector from the perspective of cash flow or EBITDA. This projected future is driven by growing and diversified revenue streams connected to our four post-phase III assets, which we believe in 2028 will generate more than $600 million in profit. The value of any firm relates back to ROIC, revenue growth, and cost of capital, and against all three metrics, we believe this firm has a rapidly improving profile over the next three years. That's less interesting to me, though, than the following fact: absent any strategic moves, our current pipeline will begin to generate cash in late 2027 and will be a cash generation engine by 2028. that's less interesting to me though than the following fact absent any strategic moves our current pipeline will begin to generate cash in late 2027 and will be a cash generation engine by 2028 The profile we anticipate having in 2028 would distinguish us in a field of genetic disease and more broadly, would place us in the top 20 to 30 firms in the biopharmaceutical sector from the perspective of cash flow or EBITDA. the profile we anticipate having in 2028 would distinguish us in a field of genetic disease and more broadly would place us in the top 20 to 30 firms in the biopharmaceutical sector from the perspective of cash flow or ebitda This projected future is driven by growing and diversified revenue streams connected to our four post-phase III assets, which we believe in 2028 will generate more than $600 million in profit. this projected future is driven by growing and diversified revenue streams connected to our four post-phase iii assets which we believe in 2028 will generate more than $600 million in profit The value of any firm relates back to ROIC, revenue growth, and cost of capital, and against all three metrics, we believe this firm has a rapidly improving profile over the next three years. the value of any firm relates back to roic revenue growth and cost of capital and against all three metrics we believe this firm has a rapidly improving profile over the next three years Our anticipated profit is even more impressive when one considers that we've been able to advance programs from the preclinical stage through phase III at under $300 million, in some cases, considerably under that, and at higher probability of technical success than industry average, suggesting an engine that could drive repeatable organic growth. Of course, all of this now highly probable growth is underpinned by clinical data that we have already generated across our four phase IIIs, as well as data that we continue to generate, and a commercial engine that continues to grow and grow share in the ATTR cardiomyopathy marketplace. We intend to establish that commercial engine as best-in-class for both first-to-market and competitive market launches in genetic disease. Despite continued strong execution across our business, our recent share price performance does not reflect the progress we've made. Our anticipated profit is even more impressive when one considers that we've been able to advance programs from the preclinical stage through phase III at under $300 million, in some cases, considerably under that, and at higher probability of technical success than industry average, suggesting an engine that could drive repeatable organic growth. our anticipated profit is even more impressive when one considers that we've been able to advance programs from the preclinical stage through phase iii at under $300 million in some cases considerably under that and at higher probability of technical success than industry average suggesting an engine that could drive repeatable organic growth Of course, all of this now highly probable growth is underpinned by clinical data that we have already generated across our four phase IIIs, as well as data that we continue to generate, and a commercial engine that continues to grow and grow share in the ATTR cardiomyopathy marketplace. of course all of this now highly probable growth is underpinned by clinical data that we have already generated across our four phase iiis as well as data that we continue to generate and a commercial engine that continues to grow and grow share in the attr cardiomyopathy marketplace We intend to establish that commercial engine as best-in-class for both first-to-market and competitive market launches in genetic disease. we intend to establish that commercial engine as best-in-class for both first-to-market and competitive market launches in genetic disease Despite continued strong execution across our business, our recent share price performance does not reflect the progress we've made. despite continued strong execution across our business our recent share price performance does not reflect the progress we've made We believe this disconnect is primarily driven by uncertainty surrounding the tafamidis IP situation, which I will address directly in a moment. Importantly, nothing about our fundamentals has deteriorated. If anything, our position is strengthened commercially, clinically, and strategically. As we execute against our milestones, we believe the intrinsic value of BridgeBio continues to increase. We are keenly aware of the gap between intrinsic value and our current market valuation, and we are actively evaluating all appropriate options to ensure that shareholder value is properly recognized over time. More specifically, over the past three months, given the de-risking of LGMD2I, our patient finding progress in ADH1, and the clearly differentiated infigratinib read out in achondroplasia, we believe our intrinsic value has increased and its error bars have narrowed. We believe this disconnect is primarily driven by uncertainty surrounding the tafamidis IP situation, which I will address directly in a moment. we believe this disconnect is primarily driven by uncertainty surrounding the tafamidis ip situation which i will address directly in a moment Importantly, nothing about our fundamentals has deteriorated. importantly nothing about our fundamentals has deteriorated If anything, our position is strengthened commercially, clinically, and strategically. if anything our position is strengthened commercially clinically and strategically As we execute against our milestones, we believe the intrinsic value of BridgeBio continues to increase. as we execute against our milestones we believe the intrinsic value of bridgebio continues to increase We are keenly aware of the gap between intrinsic value and our current market valuation, and we are actively evaluating all appropriate options to ensure that shareholder value is properly recognized over time. we are keenly aware of the gap between intrinsic value and our current market valuation and we are actively evaluating all appropriate options to ensure that shareholder value is properly recognized over time More specifically, over the past three months, given the de-risking of LGMD2I, our patient finding progress in ADH1, and the clearly differentiated infigratinib read out in achondroplasia, we believe our intrinsic value has increased and its error bars have narrowed. more specifically over the past three months given the de-risking of lgmd2i our patient finding progress in adh1 and the clearly differentiated infigratinib read out in achondroplasia we believe our intrinsic value has increased and its error bars have narrowed With over $1 billion of capital on our balance sheet and additional significant amounts of capital available away from the equity markets, and with the base business fully financed, we believe we have retained optionality to capture the value you all have helped us to create. With that said, I want to spend some time today reiterating some of the important clinical data, especially as it pertains to the infigratinib read out. I want to highlight ongoing commercial readiness activities for LGMD2I and ADH1, and I want to talk about, and Matt will elaborate on this, our continued commercial progress in ATTR cardiomyopathy. On the data side, I'll begin with our recent phase III readout in achondroplasia. As many of you know, we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile for infigratinib. With over $1 billion of capital on our balance sheet and additional significant amounts of capital available away from the equity markets, and with the base business fully financed, we believe we have retained optionality to capture the value you all have helped us to create. with over $1 billion of capital on our balance sheet and additional significant amounts of capital available away from the equity markets and with the base business fully financed we believe we have retained optionality to capture the value you all have helped us to create With that said, I want to spend some time today reiterating some of the important clinical data, especially as it pertains to the infigratinib read out. with that said i want to spend some time today reiterating some of the important clinical data especially as it pertains to the infigratinib read out I want to highlight ongoing commercial readiness activities for LGMD2I and ADH1, and I want to talk about, and Matt will elaborate on this, our continued commercial progress in ATTR cardiomyopathy. i want to highlight ongoing commercial readiness activities for lgmd2i and adh1 and i want to talk about and matt will elaborate on this our continued commercial progress in attr cardiomyopathy On the data side, I'll begin with our recent phase III readout in achondroplasia. on the data side i'll begin with our recent phase iii readout in achondroplasia As many of you know, we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile for infigratinib. as many of you know we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile for infigratinib The study successfully met the primary endpoint of change from baseline in average height velocity at week 52, with a p-value of less than 0.0001, with a mean treatment difference against placebo of 2.1 cm per year. In key secondary endpoints, infigratinib also demonstrated the first statistically significant improvement in body proportionality in achondroplasia, with a least squares mean difference of -0.05, with a p-value of less than 0.05 against placebo in children younger than eight years old, which were more than 50% of our participants, and in a pre-specified analysis. The study successfully met the primary endpoint of change from baseline in average height velocity at week 52, with a p-value of less than 0.0001, with a mean treatment difference against placebo of 2.1 cm per year. the study successfully met the primary endpoint of change from baseline in average height velocity at week 52 with a p-value of less than 0.0001 with a mean treatment difference against placebo of 2.1 cm per year In key secondary endpoints, infigratinib also demonstrated the first statistically significant improvement in body proportionality in achondroplasia, with a least squares mean difference of -0.05, with a p-value of less than 0.05 against placebo in children younger than eight years old, which were more than 50% of our participants, and in a pre-specified analysis. in key secondary endpoints infigratinib also demonstrated the first statistically significant improvement in body proportionality in achondroplasia with a least squares mean difference of -0.05 with a p-value of less than 0.05 against placebo in children younger than eight years old which were more than 50% of our participants and in a pre-specified analysis It succeeded on change from baseline in height Z-score at week 52, with a least squares mean increase on the treatment arm of 0.41 standard deviations at week 52, associated with a p-value of less than 0.0001. All of these numbers, as a reminder, are best-in-class and unique to infigratinib. Infigratinib was also well-tolerated, with no discontinuations or serious adverse events related to study drug. Three cases or 4% on active of hyperphosphatemia, considered a mild and transient, with no cases requiring either dose reduction or discontinuation, and no adverse events associated with the inhibition of FGFR1 or 2, for example, retinal or corneal adverse events. A reminder, infigratinib's differentiated oral route of administration and its mechanism, which uniquely targets this well-described condition at its source, produced phase II efficacy and safety results that were highly differentiated. It succeeded on change from baseline in height Z-score at week 52, with a least squares mean increase on the treatment arm of 0.41 standard deviations at week 52, associated with a p-value of less than 0.0001. it succeeded on change from baseline in height z-score at week 52 with a least squares mean increase on the treatment arm of 0.41 standard deviations at week 52 associated with a p-value of less than 0.0001 All of these numbers, as a reminder, are best-in-class and unique to infigratinib. all of these numbers as a reminder are best-in-class and unique to infigratinib Infigratinib was also well-tolerated, with no discontinuations or serious adverse events related to study drug. infigratinib was also well-tolerated with no discontinuations or serious adverse events related to study drug Three cases or 4% on active of hyperphosphatemia, considered a mild and transient, with no cases requiring either dose reduction or discontinuation, and no adverse events associated with the inhibition of FGFR1 or 2, for example, retinal or corneal adverse events. three cases or 4% on active of hyperphosphatemia considered a mild and transient with no cases requiring either dose reduction or discontinuation and no adverse events associated with the inhibition of fgfr1 or 2 for example retinal or corneal adverse events A reminder, infigratinib's differentiated oral route of administration and its mechanism, which uniquely targets this well-described condition at its source, produced phase II efficacy and safety results that were highly differentiated. a reminder infigratinib's differentiated oral route of administration and its mechanism which uniquely targets this well-described condition at its source produced phase ii efficacy and safety results that were highly differentiated Our phase III data have confirmed those efficacy and safety profiles. Interestingly, as we have begun to test this product profile since the readout, we have heartily found that our base case achievable market share has risen from the 52% I mentioned in my JPMorgan talk to an excess of 65% peak year share. In addition, that preliminary market research suggests not only differentiated peak year share, but also significant market expansion, similar to what we've seen when orals enter markets as diverse as Fabry, migraine, hereditary angioedema, and in many other categories. In fact, a recent analysis done at our Revenue Institute in partnership with MIT suggests that across indications, the launch of an oral product increased the sales in the category by about 170% over five years from launch of the first oral product. Our phase III data have confirmed those efficacy and safety profiles. our phase iii data have confirmed those efficacy and safety profiles Interestingly, as we have begun to test this product profile since the readout, we have heartily found that our base case achievable market share has risen from the 52% I mentioned in my JP Morgan talk to an excess of 65% peak year share. interestingly as we have begun to test this product profile since the readout we have heartily found that our base case achievable market share has risen from the 52% i mentioned in my jp morgan talk to an excess of 65% peak year share In addition, that preliminary market research suggests not only differentiated peak year share, but also significant market expansion, similar to what we've seen when orals enter markets as diverse as Fabry, migraine, hereditary angioedema, and in many other categories. in addition that preliminary market research suggests not only differentiated peak year share but also significant market expansion similar to what we've seen when orals enter markets as diverse as fabry migraine hereditary angioedema and in many other categories In fact, a recent analysis done at our Revenue Institute in partnership with MIT suggests that across indications, the launch of an oral product increased the sales in the category by about 170% over five years from launch of the first oral product. in fact a recent analysis done at our revenue institute in partnership with mit suggests that across indications the launch of an oral product increased the sales in the category by about 170% over five years from launch of the first oral product With regards to our efforts in LGMD2I, we're excited to be presenting the full data set from our study at the upcoming Muscular Dystrophy Association Conference, where Dr. Katherine Mathews from the University of Iowa will give the keynote. We have built and onboarded a dedicated commercial leadership team to ensure we are fully prepared to serve the LGMD2I community from day one. This is a population with profound unmet need, and we are ready to execute. At the same time, we are not limiting our focus to the patients already identified. We are actively working to expand awareness, accelerate diagnosis, and help uncover individuals who may be unidentified within the broader LGMD or Becker muscular dystrophy populations. Our goal is simple: to find every patient who can benefit and to ensure we are ready to reach them the moment we are able to. With regards to our efforts in LGMD2I, we're excited to be presenting the full data set from our study at the upcoming Muscular Dystrophy Association Conference, where Dr. Katherine Mathews from the University of Iowa will give the keynote. with regards to our efforts in lgmd2i we're excited to be presenting the full data set from our study at the upcoming muscular dystrophy association conference where dr katherine mathews from the university of iowa will give the keynote We have built and onboarded a dedicated commercial leadership team to ensure we are fully prepared to serve the LGMD2I community from day one. we have built and onboarded a dedicated commercial leadership team to ensure we are fully prepared to serve the lgmd2i community from day one This is a population with profound unmet need, and we are ready to execute. this is a population with profound unmet need and we are ready to execute At the same time, we are not limiting our focus to the patients already identified. at the same time we are not limiting our focus to the patients already identified We are actively working to expand awareness, accelerate diagnosis, and help uncover individuals who may be unidentified within the broader LGMD or Becker muscular dystrophy populations. we are actively working to expand awareness accelerate diagnosis and help uncover individuals who may be unidentified within the broader lgmd or becker muscular dystrophy populations Our goal is simple: to find every patient who can benefit and to ensure we are ready to reach them the moment we are able to. our goal is simple to find every patient who can benefit and to ensure we are ready to reach them the moment we are able to Moving to ADH1, our other first-in-class product, encaleret, we continue our patient-finding efforts, which have already identified in excess of 1,700 unique patients in claims data. We also recently had pre-NDA communications with the agency, which were supportive of our expectations, and we continue to anticipate the launch of both encaleret and BBP-418 in late 2026 or early 2027. Finally, and most importantly, I want to talk about our ATTR cardiomyopathy franchise, where, as I suggested recently, we continue to elaborate not only on the fullness of the best-in-class stabilizer hypothesis, but also on our differentiation in the real-world setting and our ability to impact patient health as early as one month. By far, the earliest impact we see from any medicine in this space. Moving to ADH1, our other first-in-class product, encaleret, we continue our patient-finding efforts, which have already identified in excess of 1,700 unique patients in claims data. moving to adh1 our other first-in-class product encaleret we continue our patient-finding efforts which have already identified in excess of 1,700 unique patients in claims data We also recently had pre-NDA communications with the agency, which were supportive of our expectations, and we continue to anticipate the launch of both encaleret and BBP-418 in late 2026 or early 2027. we also recently had pre-nda communications with the agency which were supportive of our expectations and we continue to anticipate the launch of both encaleret and bbp-418 in late 2026 or early 2027 Finally, and most importantly, I want to talk about our ATTR cardiomyopathy franchise, where, as I suggested recently, we continue to elaborate not only on the fullness of the best-in-class stabilizer hypothesis, but also on our differentiation in the real-world setting and our ability to impact patient health as early as one month. finally and most importantly i want to talk about our attr cardiomyopathy franchise where as i suggested recently we continue to elaborate not only on the fullness of the best-in-class stabilizer hypothesis but also on our differentiation in the real-world setting and our ability to impact patient health as early as one month By far, the earliest impact we see from any medicine in this space. by far the earliest impact we see from any medicine in this space We already pre-announced the fourth quarter Attruby net product revenue of $146 million, which corresponded to greater than 25% MBRX share as of December 31st, 2025. Over the last few weeks, Attruby's commercial momentum has continued. As of February 20th, we have seen 7,804 unique patient prescriptions written by 1,856 unique prescribers. You'll hear more from Matt about what this means in terms of competitive differentiation, and as I alluded to as well in my JPM talk, we are continuing to interrogate the importance of the cardiorenal axis, which seems to be uniquely involved in our early onset of action. We already pre-announced the fourth quarter Attruby net product revenue of $146 million, which corresponded to greater than 25% MBRX share as of December 31st, 2025. we already pre-announced the fourth quarter attruby net product revenue of $146 million which corresponded to greater than 25% mbrx share as of december 31st 2025 Over the last few weeks, Attruby's commercial momentum has continued. over the last few weeks attruby's commercial momentum has continued As of February 20th, we have seen 7,804 unique patient prescriptions written by 1,856 unique prescribers. as of february 20th we have seen 7,804 unique patient prescriptions written by 1,856 unique prescribers You'll hear more from Matt about what this means in terms of competitive differentiation, and as I alluded to as well in my JPM talk, we are continuing to interrogate the importance of the cardiorenal axis, which seems to be uniquely involved in our early onset of action. you'll hear more from matt about what this means in terms of competitive differentiation and as i alluded to as well in my jpm talk we are continuing to interrogate the importance of the cardiorenal axis which seems to be uniquely involved in our early onset of action We have also noted with great interest the recent PNAS paper, that I only had a bit of time to talk about at JPMorgan, which suggests that binding enthalpy best predicts the conformational stabilization imparted by kinetic stabilizers, as opposed to binding affinity, KD or Gibbs free energy. As we have shown through ITC experiments and as we published in Miller et al., we have a vastly superior enthalpic binding mode than does tafamidis, which, in concert with superior binding kinetics, continues to reinforce Attruby's better stabilization profile. A recent bevy of literature further supports that increases in serum TTR are associated reliably with decreases in the relative risk of mortality. These papers suggest that for every mg per dL increase in serum TTR, you decrease the risk of mortality at 30 months by approximately 5%. We have also noted with great interest the recent PNAS paper, that I only had a bit of time to talk about at JP Morgan, which suggests that binding enthalpy best predicts the conformational stabilization imparted by kinetic stabilizers, as opposed to binding affinity, KD or Gibbs free energy. we have also noted with great interest the recent pnas paper that i only had a bit of time to talk about at jp morgan which suggests that binding enthalpy best predicts the conformational stabilization imparted by kinetic stabilizers as opposed to binding affinity kd or gibbs free energy As we have shown through ITC experiments and as we published in Miller et al., we have a vastly superior enthalpic binding mode than does tafamidis, which, in concert with superior binding kinetics, continues to reinforce Attruby's better stabilization profile. as we have shown through itc experiments and as we published in miller et al we have a vastly superior enthalpic binding mode than does tafamidis which in concert with superior binding kinetics continues to reinforce attruby's better stabilization profile A recent bevy of literature further supports that increases in serum TTR are associated reliably with decreases in the relative risk of mortality. a recent bevy of literature further supports that increases in serum ttr are associated reliably with decreases in the relative risk of mortality These papers suggest that for every mg per dL increase in serum TTR, you decrease the risk of mortality at 30 months by approximately 5%. these papers suggest that for every mg per dl increase in serum ttr you decrease the risk of mortality at 30 months by approximately 5% As a reminder, we observed in our phase III study that patients increased their serum TTR by 3 mgs/dL when moving from tafamidis to acoramidis. This suggests a whopping 15% relative risk reduction in mortality when moving from tafamidis to acoramidis. Let me also address the recent stock volatility, which is largely centered on questions regarding Vyndamax IP and the potential for generic entry. It's important to separate two things: the legal process around tafamidis and the fundamental strength of Attruby. Our confidence in Attruby is rooted in its clinical profile and market positioning, not a particular IP outcome. On the IP front, the Pfizer decision to withdraw one of its EU patents defending the Vyndamax equivalent product was unexpected. As a reminder, we observed in our phase III study that patients increased their serum TTR by 3 mgs/ dL when moving from tafamidis to acoramidis. as a reminder we observed in our phase iii study that patients increased their serum ttr by 3 mgs/ dl when moving from tafamidis to acoramidis This suggests a whopping 15% relative risk reduction in mortality when moving from tafamidis to acoramidis. this suggests a whopping 15% relative risk reduction in mortality when moving from tafamidis to acoramidis Let me also address the recent stock volatility, which is largely centered on questions regarding Vyndamax IP and the potential for generic entry. let me also address the recent stock volatility which is largely centered on questions regarding vyndamax ip and the potential for generic entry It's important to separate two things: the legal process around tafamidis and the fundamental strength of Attruby. it's important to separate two things the legal process around tafamidis and the fundamental strength of attruby Our confidence in Attruby is rooted in its clinical profile and market positioning, not a particular IP outcome. our confidence in attruby is rooted in its clinical profile and market positioning not a particular ip outcome On the IP front, the Pfizer decision to withdraw one of its EU patents defending the Vyndamax equivalent product was unexpected. on the ip front the pfizer decision to withdraw one of its eu patents defending the vyndamax equivalent product was unexpected That said, it did not materially change how we view the EU market, given Vyndamax's Orphan Drug Exclusivity in wild-type ATTR cardiomyopathy through 2030, which is now and how we have always consistently modeled that geography. In the U.S., which is the market of greatest importance to us, we believe the IP position is stronger. The patent claims at issue are narrower than those in Europe, including specific XRPD peak limitations for Form 1 that were not part of the EU case. In addition, U.S. law applies a higher legal threshold for invalidity, requiring that challengers prove by clear and convincing evidence that a prior art process necessarily and inevitably produces the claimed form, not merely that it could or likely would. That said, IP trials are inherently uncertain, and we will reassess as more information comes available following the U.S. proceedings in April. That said, it did not materially change how we view the EU market, given Vyndamax's Orphan Drug Exclusivity in wild-type ATTR cardiomyopathy through 2030, which is now and how we have always consistently modeled that geography. that said it did not materially change how we view the eu market given vyndamax's orphan drug exclusivity in wild-type attr cardiomyopathy through 2030 which is now and how we have always consistently modeled that geography In the U.S., which is the market of greatest importance to us, we believe the IP position is stronger. in the u.s which is the market of greatest importance to us we believe the ip position is stronger The patent claims at issue are narrower than those in Europe, including specific XRPD peak limitations for Form 1 that were not part of the EU case. the patent claims at issue are narrower than those in europe including specific xrpd peak limitations for form 1 that were not part of the eu case In addition, U.S. law applies a higher legal threshold for invalidity, requiring that challengers prove by clear and convincing evidence that a prior art process necessarily and inevitably produces the claimed form, not merely that it could or likely would. in addition u.s law applies a higher legal threshold for invalidity requiring that challengers prove by clear and convincing evidence that a prior art process necessarily and inevitably produces the claimed form not merely that it could or likely would That said, IP trials are inherently uncertain, and we will reassess as more information comes available following the U.S. proceedings in April. that said ip trials are inherently uncertain and we will reassess as more information comes available following the u.s proceedings in april Stepping back, however, our strategy does not depend on tafamidis IP. Attruby has demonstrated near complete stabilization, rapid clinical benefit, and meaningful differentiation in ATTR cardiomyopathy. It is already priced at a discount to Vyndamax and is less than half the price of the knockdown technologies. We believe physicians are making decisions based on clinical performance, not simply price, and prescribing trends we are seeing are reflecting that. Even in a hypothetical scenario involving generic tafamidis, we do not believe a less efficacious product would undermine the role of a clinically differentiated therapy in a serious progressive disease like ATTR-CM. In short, we remain confident in Attruby's positioning today and in the years ahead. With that, I'll turn it over to Matt to speak more specifically about the commercial momentum we're seeing. Stepping back, however, our strategy does not depend on tafamidis IP. stepping back however our strategy does not depend on tafamidis ip Attruby has demonstrated near complete stabilization, rapid clinical benefit, and meaningful differentiation in ATTR cardiomyopathy. attruby has demonstrated near complete stabilization rapid clinical benefit and meaningful differentiation in attr cardiomyopathy It is already priced at a discount to Vyndamax and is less than half the price of the knockdown technologies. it is already priced at a discount to vyndamax and is less than half the price of the knockdown technologies We believe physicians are making decisions based on clinical performance, not simply price, and prescribing trends we are seeing are reflecting that. we believe physicians are making decisions based on clinical performance not simply price and prescribing trends we are seeing are reflecting that Even in a hypothetical scenario involving generic tafamidis, we do not believe a less efficacious product would undermine the role of a clinically differentiated therapy in a serious progressive disease like ATTR-CM. even in a hypothetical scenario involving generic tafamidis we do not believe a less efficacious product would undermine the role of a clinically differentiated therapy in a serious progressive disease like attr-cm In short, we remain confident in Attruby's positioning today and in the years ahead. in short we remain confident in attruby's positioning today and in the years ahead With that, I'll turn it over to Matt to speak more specifically about the commercial momentum we're seeing. with that i'll turn it over to matt to speak more specifically about the commercial momentum we're seeing

Speaker 8: Thank you, Neil. Consistent with what we highlighted at JPMorgan in January, we believe 2025 reflected strong commercial momentum for Attruby, and it represented an important step forward in advancing three additional product candidates towards potential commercialization. In the fourth quarter, we delivered 35% quarter-over-quarter growth in net product revenue, ending the year with $502.1 million in total revenue and $154.2 million in quarter four. Of this, the net product revenue for Attruby was $362.4 million and $146 million, respectively, while new patient growth accelerated in the latest quarter to reach 7,804 new patient starts. Thank you, Neil. thank you neil Consistent with what we highlighted at JP Morgan in January, we believe 2025 reflected strong commercial momentum for Attruby, and it represented an important step forward in advancing three additional product candidates towards potential commercialization. consistent with what we highlighted at jp morgan in january we believe 2025 reflected strong commercial momentum for attruby and it represented an important step forward in advancing three additional product candidates towards potential commercialization In the fourth quarter, we delivered 35% quarter-over-quarter growth in net product revenue, ending the year with $502.1 million in total revenue and $154.2 million in quarter four. in the fourth quarter we delivered 35% quarter-over-quarter growth in net product revenue ending the year with $502.1 million in total revenue and $154.2 million in quarter four Of this, the net product revenue for Attruby was $362.4 million and $146 million, respectively, while new patient growth accelerated in the latest quarter to reach 7,804 new patient starts. of this the net product revenue for attruby was $362.4 million and $146 million respectively while new patient growth accelerated in the latest quarter to reach 7,804 new patient starts When viewed in conjunction with the IQVIA data, it becomes clear that Attruby is accelerating growth at a significantly faster rate versus previous quarters, while the competition lags behind. This is particularly obvious in first-line patients, where the exceptional data for Attruby, along with our experienced field teams, have driven sales to the highest levels since launch, surpassing all expectations. We have historically given out the new patient start number each quarter and have done so again, despite the competition not offering similar numbers. Moving forward, we will not be offering new patient start data because of this lack of transparency by others. Continuing to do so would put us in a competitive disadvantage, but our expectations are that Attruby will continue to grow as it has done since launch and as exemplified with today's update. When viewed in conjunction with the IQVIA data, it becomes clear that Attruby is accelerating growth at a significantly faster rate versus previous quarters, while the competition lags behind. when viewed in conjunction with the iqvia data it becomes clear that attruby is accelerating growth at a significantly faster rate versus previous quarters while the competition lags behind This is particularly obvious in first-line patients, where the exceptional data for Attruby, along with our experienced field teams, have driven sales to the highest levels since launch, surpassing all expectations. this is particularly obvious in first-line patients where the exceptional data for attruby along with our experienced field teams have driven sales to the highest levels since launch surpassing all expectations We have historically given out the new patient start number each quarter and have done so again, despite the competition not offering similar numbers. we have historically given out the new patient start number each quarter and have done so again despite the competition not offering similar numbers Moving forward, we will not be offering new patient start data because of this lack of transparency by others. moving forward we will not be offering new patient start data because of this lack of transparency by others Continuing to do so would put us in a competitive disadvantage, but our expectations are that Attruby will continue to grow as it has done since launch and as exemplified with today's update. continuing to do so would put us in a competitive disadvantage but our expectations are that attruby will continue to grow as it has done since launch and as exemplified with today's update As adoption grows, particularly in the first-line setting, we remain focused on ensuring patients and healthcare professionals have clear, balanced information when evaluating therapy options. That focus is especially relevant given recent updates we've seen in competitor direct-to-consumer communications. After receiving a letter from the FDA several months ago and pulling their television ad from the airwaves, Alnylam has returned to TV advertising, but of note, the safety section has been updated. Besides adding the warning about the risk of eplontersen lowering vitamin A and potentially affecting vision, the ad now points out the risk for several additional concerns, namely joint pain, pain in the arms and legs, and shortness of breath. As adoption grows, particularly in the first-line setting, we remain focused on ensuring patients and healthcare professionals have clear, balanced information when evaluating therapy options. as adoption grows particularly in the first-line setting we remain focused on ensuring patients and healthcare professionals have clear balanced information when evaluating therapy options That focus is especially relevant given recent updates we've seen in competitor direct-to-consumer communications. that focus is especially relevant given recent updates we've seen in competitor direct-to-consumer communications After receiving a letter from the FDA several months ago and pulling their television ad from the airwaves, Alnylam has returned to TV advertising, but of note, the safety section has been updated. after receiving a letter from the fda several months ago and pulling their television ad from the airwaves alnylam has returned to tv advertising but of note the safety section has been updated Besides adding the warning about the risk of eplontersen lowering vitamin A and potentially affecting vision, the ad now points out the risk for several additional concerns, namely joint pain, pain in the arms and legs, and shortness of breath. besides adding the warning about the risk of eplontersen lowering vitamin a and potentially affecting vision the ad now points out the risk for several additional concerns namely joint pain, pain in the arms and legs and shortness of breath In a population already often suffering from these issues, the possibilities of amplifying, compounding, or causing shortness of breath and/or pain in the joints and/or pain in the arms and/or pain in the legs should be highlighted to any patient considering treatment with eplontersen. The fact that these risks had been omitted but are now stated at the end of each commercial, and hopefully all promotional materials and messaging, will correct and highlight for patients and healthcare professionals some things to consider with eplontersen treatment, especially if they are a newly diagnosed patient versus someone who has tried all other options. If we shift back to the reasons for the growth of Attruby, there are several driving factors. First, the number of prescribing HCPs continues to grow, but of equal importance, HCPs who start using Attruby continue using Attruby. In a population already often suffering from these issues, the possibilities of amplifying, compounding, or causing shortness of breath and/or pain in the joints and/or pain in the arms and/or pain in the legs should be highlighted to any patient considering treatment with eplontersen. in a population already often suffering from these issues the possibilities of amplifying compounding or causing shortness of breath and/or pain in the joints and/or pain in the arms and/or pain in the legs should be highlighted to any patient considering treatment with eplontersen The fact that these risks had been omitted but are now stated at the end of each commercial, and hopefully all promotional materials and messaging, will correct and highlight for patients and healthcare professionals some things to consider with eplontersen treatment, especially if they are a newly diagnosed patient versus someone who has tried all other options. the fact that these risks had been omitted but are now stated at the end of each commercial and hopefully all promotional materials and messaging will correct and highlight for patients and healthcare professionals some things to consider with eplontersen treatment especially if they are a newly diagnosed patient versus someone who has tried all other options If we shift back to the reasons for the growth of Attruby, there are several driving factors. if we shift back to the reasons for the growth of attruby there are several driving factors First, the number of prescribing HCPs continues to grow, but of equal importance, HCPs who start using Attruby continue using Attruby. first the number of prescribing hcps continues to grow but of equal importance hcps who start using attruby continue using attruby We are seeing repeat use and stable patient persistence, which tells us physicians are comfortable with what they are seeing in their practice. We believe the success we have seen in 2025 is driven by Attruby's differentiated profile as the only near-complete stabilizer on the market, in contrast to therapies that rely on partial stabilization or partial knockdown mechanisms of action. Attruby has also demonstrated the fastest time to separation to date, an attribute that matters as physicians seek therapies that can deliver meaningful benefit quickly. Importantly, persistency and adherence for Attruby continue to exceed our original expectations, which were based on historical ATTR treatment patterns, reinforcing our confidence in the durability of the franchise. We believe we have the strongest commercial teams in the industry, spanning sales, marketing, strategy, analytics, and market access. We are seeing repeat use and stable patient persistence, which tells us physicians are comfortable with what they are seeing in their practice. we are seeing repeat use and stable patient persistence which tells us physicians are comfortable with what they are seeing in their practice We believe the success we have seen in 2025 is driven by Attruby's differentiated profile as the only near-complete stabilizer on the market, in contrast to therapies that rely on partial stabilization or partial knockdown mechanisms of action. we believe the success we have seen in 2025 is driven by attruby's differentiated profile as the only near-complete stabilizer on the market in contrast to therapies that rely on partial stabilization or partial knockdown mechanisms of action Attruby has also demonstrated the fastest time to separation to date, an attribute that matters as physicians seek therapies that can deliver meaningful benefit quickly. attruby has also demonstrated the fastest time to separation to date an attribute that matters as physicians seek therapies that can deliver meaningful benefit quickly Importantly, persistency and adherence for Attruby continue to exceed our original expectations, which were based on historical ATTR treatment patterns, reinforcing our confidence in the durability of the franchise. importantly persistency and adherence for attruby continue to exceed our original expectations which were based on historical attr treatment patterns reinforcing our confidence in the durability of the franchise We believe we have the strongest commercial teams in the industry, spanning sales, marketing, strategy, analytics, and market access. we believe we have the strongest commercial teams in the industry spanning sales marketing strategy analytics and market access Many team members have worked together for years. We've continued to build on that foundation with targeted hiring of top talent, including the recent expansion of the Atrusi sales team. Overall, Q4 reflects continued progress across key metrics, including growth in patients on therapy and ongoing use by prescribers. We are excited to see continued growth in quarter one as we head into 2026. Turning to the pipeline, we are focused on the next wave of potential launches. We are excited by the recent clinical results for BBP-418, encaleret, and infigratinib, all of which exceeded expectations across their primary and secondary endpoints. Based on the strength of these data, we believe each program will be the leader in its respective market and bring much-needed therapies to families and patients in need of care. Many team members have worked together for years. many team members have worked together for years We've continued to build on that foundation with targeted hiring of top talent, including the recent expansion of the Atrusi sales team. we've continued to build on that foundation with targeted hiring of top talent including the recent expansion of the atrusi sales team Overall, Q4 reflects continued progress across key metrics, including growth in patients on therapy and ongoing use by prescribers. overall q4 reflects continued progress across key metrics including growth in patients on therapy and ongoing use by prescribers We are excited to see continued growth in quarter one as we head into 2026. we are excited to see continued growth in quarter one as we head into 2026 Turning to the pipeline, we are focused on the next wave of potential launches. turning to the pipeline we are focused on the next wave of potential launches We are excited by the recent clinical results for BBP-418, encaleret, and infigratinib, all of which exceeded expectations across their primary and secondary endpoints. we are excited by the recent clinical results for bbp-418, encaleret and infigratinib all of which exceeded expectations across their primary and secondary endpoints Based on the strength of these data, we believe each program will be the leader in its respective market and bring much-needed therapies to families and patients in need of care. based on the strength of these data we believe each program will be the leader in its respective market and bring much-needed therapies to families and patients in need of care Building on the successful launch of Attruby, we have established a proven commercial foundation and are well-positioned to extend this model as we prepare for future launches across our pipeline. We look forward to going into more detail as we get closer to approval for each. I will now turn the call over to Tom. Building on the successful launch of Attruby, we have established a proven commercial foundation and are well-positioned to extend this model as we prepare for future launches across our pipeline. building on the successful launch of attruby we have established a proven commercial foundation and are well-positioned to extend this model as we prepare for future launches across our pipeline We look forward to going into more detail as we get closer to approval for each. we look forward to going into more detail as we get closer to approval for each I will now turn the call over to Tom. i will now turn the call over to tom

Speaker 11: Thank you, Matt, and good afternoon, everyone. I'll now discuss our financial results for the fourth quarter and full year of 2025. Please note that our commentary on today's call will focus on GAAP financials, unless otherwise indicated. Total revenues were $154.2 million in 4Q 2025, consisting of $146 million of Attruby net product revenue, $5.3 million of royalty revenue, and $2.9 million of license and service revenue, compared to total revenues of $5.9 million for the same period last year. Thank you, Matt, and good afternoon, everyone. thank you matt and good afternoon everyone I'll now discuss our financial results for the fourth quarter and full year of 2025. i'll now discuss our financial results for the fourth quarter and full year of 2025 Please note that our commentary on today's call will focus on GAAP financials, unless otherwise indicated. please note that our commentary on today's call will focus on gaap financials unless otherwise indicated Total revenues were $154.2 million in 4Q 2025, consisting of $146 million of Attruby net product revenue, $5.3 million of royalty revenue, and $2.9 million of license and service revenue, compared to total revenues of $5.9 million for the same period last year. total revenues were $154.2 million in 4q 2025 consisting of $146 million of attruby net product revenue $5.3 million of royalty revenue and $2.9 million of license and service revenue compared to total revenues of $5.9 million for the same period last year The $148.3 million increase in total revenues was primarily driven by a $143.1 million increase in net product revenue from Attruby, reflecting broad-based growth across market segments, including accelerating first-line adoption, increasing new patient starts, expanding prescriber depth, and strong persistency and adherence, supporting durable revenue growth. We also recorded an increase of $5.1 million in royalty revenue from ex U.S. net sales of Beyonttra in Europe and Japan. For the full year 2025, total revenues were $502.1 million, compared to $221.9 million for the full year 2024. The $148.3 million increase in total revenues was primarily driven by a $143.1 million increase in net product revenue from Attruby, reflecting broad-based growth across market segments, including accelerating first-line adoption, increasing new patient starts, expanding prescriber depth, and strong persistency and adherence, supporting durable revenue growth. the $148.3 million increase in total revenues was primarily driven by a $143.1 million increase in net product revenue from attruby reflecting broad-based growth across market segments including accelerating first-line adoption increasing new patient starts expanding prescriber depth and strong persistency and adherence supporting durable revenue growth We also recorded an increase of $5.1 million in royalty revenue from ex U.S. net sales of Beyonttra in Europe and Japan. we also recorded an increase of $5.1 million in royalty revenue from ex u.s net sales of beyonttra in europe and japan For the full year 2025, total revenues were $502.1 million, compared to $221.9 million for the full year 2024. for the full year 2025 total revenues were $502.1 million compared to $221.9 million for the full year 2024 The $280.2 million increase in total revenues for the full year was primarily due to $359.5 million increase in net product revenue from Attruby and an $11.2 million increase in royalty revenue from sales of Beyonttra, partially offset by a $90.5 million decrease in license and service revenues versus the prior year. Total operating costs and expenses for the fourth quarter of 2025 were $293.7 million, compared to $231.9 million in the same period in the prior year. The $280.2 million increase in total revenues for the full year was primarily due to $359.5 million increase in net product revenue from Attruby and an $11.2 million increase in royalty revenue from sales of Beyonttra, partially offset by a $90.5 million decrease in license and service revenues versus the prior year. the $280.2 million increase in total revenues for the full year was primarily due to $359.5 million increase in net product revenue from attruby and an $11.2 million increase in royalty revenue from sales of beyonttra partially offset by a $90.5 million decrease in license and service revenues versus the prior year Total operating costs and expenses for the fourth quarter of 2025 were $293.7 million, compared to $231.9 million in the same period in the prior year. total operating costs and expenses for the fourth quarter of 2025 were $293.7 million compared to $231.9 million in the same period in the prior year The $61.8 million increase in operating costs and expenses was primarily driven by a $63.3 million increase in SG&A expenses, partially offset by a $13.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. For the full year 2025, total operating costs and expenses were $1 billion, compared to $814.9 million in the prior year. The $210.6 million increase was primarily driven by a $242.3 million increase in SG&A, largely reflecting the company's investments to support the commercial launch and ongoing activities for Attruby. The $61.8 million increase in operating costs and expenses was primarily driven by a $63.3 million increase in SG&A expenses, partially offset by a $13.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. the $61.8 million increase in operating costs and expenses was primarily driven by a $63.3 million increase in sg&a expenses partially offset by a $13.9 million decrease in r&d expenses primarily due to decreased r&d activities related to attruby and beyonttra following regulatory approval For the full year 2025, total operating costs and expenses were $1 billion, compared to $814.9 million in the prior year. for the full year 2025 total operating costs and expenses were $1 billion compared to $814.9 million in the prior year The $210.6 million increase was primarily driven by a $242.3 million increase in SG&A, largely reflecting the company's investments to support the commercial launch and ongoing activities for Attruby. the $210.6 million increase was primarily driven by a $242.3 million increase in sg&a largely reflecting the company's investments to support the commercial launch and ongoing activities for attruby This increase was partially offset by a $54.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. Turning to our balance sheet, we ended the year with a cash position of $587.5 million in cash equivalents, and marketable securities. We completed the issuance of $632.5 million aggregate principal amount of 2033 convertible notes in January 2026, which provides significant cash runway to continue supporting our transition into a diversified, late-stage, multi-product business. With that, I'll turn the call back over to Chinmay. This increase was partially offset by a $54.9 million decrease in R&D expenses, primarily due to decreased R&D activities related to Attruby and Beyonttra following regulatory approval. this increase was partially offset by a $54.9 million decrease in r&d expenses primarily due to decreased r&d activities related to attruby and beyonttra following regulatory approval Turning to our balance sheet, we ended the year with a cash position of $587.5 million in cash equivalents, and marketable securities. turning to our balance sheet we ended the year with a cash position of $587.5 million in cash equivalents and marketable securities We completed the issuance of $632.5 million aggregate principal amount of 2033 convertible notes in January 2026, which provides significant cash runway to continue supporting our transition into a diversified, late-stage, multi-product business. we completed the issuance of $632.5 million aggregate principal amount of 2033 convertible notes in january 2026 which provides significant cash runway to continue supporting our transition into a diversified late-stage multi-product business With that, I'll turn the call back over to Chinmay. with that i'll turn the call back over to chinmay

Speaker 4: Thank you, Neil, Matt, and Tom. We will now turn the call over to the operator, who will open the line for questions. Thank you. Thank you, Neil, Matt, and Tom. thank you neil matt and tom We will now turn the call over to the operator, who will open the line for questions. we will now turn the call over to the operator who will open the line for questions Thank you. thank you

Speaker 10: At this time, I'd like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We'll pause for just a brief moment to compile the Q&A roster. Your first question comes from the line of Salim Syed from Mizuho. Your line is live. At this time, I'd like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. at this time i'd like to remind everyone in order to ask a question press star then the number one on your telephone keypad We'll pause for just a brief moment to compile the Q&A roster. we'll pause for just a brief moment to compile the q&a roster Your first question comes from the line of Salim Syed from Mizuho. your first question comes from the line of salim syed from mizuho Your line is live. your line is live

Speaker 13: Hi, guys. This is Bennett for Salim. Thanks for taking our question. Congrats on another quarter of continued patient growth. If I may, could you comment on why Attruby continues to show consistent growth even as competitors' growth seem to be slowing down? I mean, can you comment on what are the key drivers behind it, what is the feedback that you feel is resonating more with docs and patients now that we are several quarters in? Thank you. Hi, guys. hi guys This is Bennett for Salim. this is bennett for salim Thanks for taking our question. thanks for taking our question Congrats on another quarter of continued patient growth. congrats on another quarter of continued patient growth If I may, could you comment on why Attruby continues to show consistent growth even as competitors' growth seem to be slowing down? if i may could you comment on why attruby continues to show consistent growth even as competitors' growth seem to be slowing down I mean, can you comment on what are the key drivers behind it, what is the feedback that you feel is resonating more with docs and patients now that we are several quarters in? i mean can you comment on what are the key drivers behind it what is the feedback that you feel is resonating more with docs and patients now that we are several quarters in Thank you. thank you

Speaker 9: Thanks, Bennett. Maybe I'll turn it to, Matt to answer that question. Thanks, Bennett. thanks bennett Maybe I'll turn it to, Matt to answer that question. maybe i'll turn it to matt to answer that question

Speaker 8: Sure. Thanks. I think it's multifaceted, but a big part is the field team that we have at BridgeBio. The right team makes or breaks a launch, and that's across both commercial and medical. Of course, there's the data. No one's been able to show better data or near complete stabilization, only Attruby. I think the time to separation is a big factor, and you heard some of that in the earlier comments. I think finally, we've stayed disciplined and focused on what's important for patients and HCPs. We have category-leading efficacy and safety with consistent results across all patient types. A great team and a great medicine, I think it's hard to slow down. Sure. sure Thanks. thanks I think it's multifaceted, but a big part is the field team that we have at BridgeBio. i think it's multifaceted but a big part is the field team that we have at bridgebio The right team makes or breaks a launch, and that's across both commercial and medical. the right team makes or breaks a launch and that's across both commercial and medical Of course, there's the data. of course there's the data No one's been able to show better data or near complete stabilization, only Attruby. no one's been able to show better data or near complete stabilization only attruby I think the time to separation is a big factor, and you heard some of that in the earlier comments. i think the time to separation is a big factor and you heard some of that in the earlier comments I think finally, we've stayed disciplined and focused on what's important for patients and HCPs. i think finally we've stayed disciplined and focused on what's important for patients and hcps We have category-leading efficacy and safety with consistent results across all patient types. we have category-leading efficacy and safety with consistent results across all patient types A great team and a great medicine, I think it's hard to slow down. a great team and a great medicine i think it's hard to slow down

Speaker 9: Maybe I'll just build on that. You can, you can see in the new patient script number something kind of interesting where we had that rapid acceleration at first, sort of plateaued, and now we have a second wave of acceleration. That's sort of rare if you look and model most launches, where you see kind of a burst of activity and then, and then typically you see a slowing. That really portends one of two things. One is obviously rapid patient identification, which I think we are seeing in the field. Secondly, it's really a second wave of prescribers that are starting to wake up to some of the messages that we're putting forth. That, I think, is an exciting profile generally for a launch this early in. Maybe I'll just build on that. maybe i'll just build on that You can, you can see in the new patient script number something kind of interesting where we had that rapid acceleration at first, sort of plateaued, and now we have a second wave of acceleration. you can you can see in the new patient script number something kind of interesting where we had that rapid acceleration at first sort of plateaued and now we have a second wave of acceleration That's sort of rare if you look and model most launches, where you see kind of a burst of activity and then, and then typically you see a slowing. that's sort of rare if you look and model most launches where you see kind of a burst of activity and then and then typically you see a slowing That really portends one of two things. that really portends one of two things One is obviously rapid patient identification, which I think we are seeing in the field. one is obviously rapid patient identification which i think we are seeing in the field Secondly, it's really a second wave of prescribers that are starting to wake up to some of the messages that we're putting forth. secondly it's really a second wave of prescribers that are starting to wake up to some of the messages that we're putting forth That, I think, is an exciting profile generally for a launch this early in. that i think is an exciting profile generally for a launch this early in You know, couple that with nearly 1,200 new scripts since I gave my JPM talk, that's a very, very exciting trajectory right now. You know, couple that with nearly 1,200 new scripts since I gave my JPM talk, that's a very, very exciting trajectory right now. you know couple that with nearly 1,200 new scripts since i gave my jpm talk that's a very very exciting trajectory right now

Speaker 13: All right. Thank you. All right. all right Thank you. thank you

Speaker 10: Your next question comes from the line of Mani Foroohar from Leerink Partners. Your line is live. Your next question comes from the line of Mani Foroohar from Leerink Partners. your next question comes from the line of mani foroohar from leerink partners Your line is live. your line is live

Speaker 7: Hey, thanks, guys. Congrats on continuing to show volume growth in the face of competitors who are seeing slowdowns. You've talked a lot about the commercial differentiation and differences in your growth trajectory versus competitors. Lots of different pieces of data go into that. I want to look past out into just what the timeline is into whenever tafamidis gets generic and beyond, about clinical differentiation, which you've identified as core to your strategy to driving continued growth and durability in the face of a generic whenever that happens. Can you tell us when we'll have significant incremental real-world data, longer-term data from acoramidis to establish that difference in clinical benefit that you guys are hanging that growth tail on? Hey, thanks, guys. hey thanks guys Congrats on continuing to show volume growth in the face of competitors who are seeing slowdowns. congrats on continuing to show volume growth in the face of competitors who are seeing slowdowns You've talked a lot about the commercial differentiation and differences in your growth trajectory versus competitors. you've talked a lot about the commercial differentiation and differences in your growth trajectory versus competitors Lots of different pieces of data go into that. lots of different pieces of data go into that I want to look past out into just what the timeline is into whenever tafamidis gets generic and beyond, about clinical differentiation, which you've identified as core to your strategy to driving continued growth and durability in the face of a generic whenever that happens. i want to look past out into just what the timeline is into whenever tafamidis gets generic and beyond about clinical differentiation which you've identified as core to your strategy to driving continued growth and durability in the face of a generic whenever that happens Can you tell us when we'll have significant incremental real-world data, longer-term data from acoramidis to establish that difference in clinical benefit that you guys are hanging that growth tail on? can you tell us when we'll have significant incremental real-world data longer-term data from acoramidis to establish that difference in clinical benefit that you guys are hanging that growth tail on

Speaker 9: Yeah. Great question, Mani. Thanks for it. you know, I think first, the key is for us to really start to get some of the data that we presented in the last year out into the field and understood. Maybe just a couple pieces that I think have been overlooked or are just starting to really make their way into the field. First and foremost is the early impact, that impact as early as one month that I talked about at JPM. We continue to interrogate the precise mechanism behind it. As you know from these clinical trials and a lot of the real-world evidence, early CVH is extremely common. You want to get patients on the drug that can take action as early as possible. Yeah. yeah Great question, Mani. great question mani Thanks for it. you know, I think first, the key is for us to really start to get some of the data that we presented in the last year out into the field and understood. thanks for it you know i think first the key is for us to really start to get some of the data that we presented in the last year out into the field and understood Maybe just a couple pieces that I think have been overlooked or are just starting to really make their way into the field. maybe just a couple pieces that i think have been overlooked or are just starting to really make their way into the field First and foremost is the early impact, that impact as early as one month that I talked about at JPM. first and foremost is the early impact that impact as early as one month that i talked about at jpm We continue to interrogate the precise mechanism behind it. we continue to interrogate the precise mechanism behind it As you know from these clinical trials and a lot of the real-world evidence, early CVH is extremely common. as you know from these clinical trials and a lot of the real-world evidence early cvh is extremely common You want to get patients on the drug that can take action as early as possible. you want to get patients on the drug that can take action as early as possible Not only for that reason, obviously this is an ongoing mass action and deleterious disease, so you wanna be on the drug that has the earliest impact. The second is, the AF data that we put forth. You know, nearly 60% of patients in this space suffer from AF or cardiac arrhythmic events. I think the most important piece of the data that we put forth when we showed the 17% reduction, as published last year, is that we're having an equivalent effect on or off in AF, in the AF subpopulation. So, you know, when you think about AF patients being slightly harder to manage in the context of ATTR cardiomyopathy, here you have a drug that has consistent and high impact. Not only for that reason, obviously this is an ongoing mass action and deleterious disease, so you wanna be on the drug that has the earliest impact. not only for that reason obviously this is an ongoing mass action and deleterious disease so you wanna be on the drug that has the earliest impact The second is, the AF data that we put forth. the second is the af data that we put forth You know, nearly 60% of patients in this space suffer from AF or cardiac arrhythmic events. you know nearly 60% of patients in this space suffer from af or cardiac arrhythmic events I think the most important piece of the data that we put forth when we showed the 17% reduction, as published last year, is that we're having an equivalent effect on or off in AF, in the AF subpopulation. i think the most important piece of the data that we put forth when we showed the 17% reduction as published last year is that we're having an equivalent effect on or off in af in the af subpopulation So, you know, when you think about AF patients being slightly harder to manage in the context of ATTR cardiomyopathy, here you have a drug that has consistent and high impact. so you know when you think about af patients being slightly harder to manage in the context of attr cardiomyopathy here you have a drug that has consistent and high impact In fact, the highest point estimate we've seen in terms of both reduction in downstream outcomes of 43% and reduction in AF itself of 17%. That I think, is the second piece that we need to do a better job of educating on, and I think physicians will find it exciting. Finally, it's the variant population, right? The sickest by far, of the subpopulations. They do deserve a better drug, and that 0.41 hazard ratio that we presented on with statistical significance, even more impressive given the fact that less than 10% of our patients on Attruby were a variant patients. I think that is the best point estimate, again, with the best statistical significance in the space, and extremely consistent with the binding mode that we've articulated, which is differentiated against tafamidis. In fact, the highest point estimate we've seen in terms of both reduction in downstream outcomes of 43% and reduction in AF itself of 17%. in fact, the highest point estimate we've seen in terms of both reduction in downstream outcomes of 43% and reduction in af itself of 17% That I think, is the second piece that we need to do a better job of educating on, and I think physicians will find it exciting. that i think is the second piece that we need to do a better job of educating on and i think physicians will find it exciting Finally, it's the variant population, right? finally it's the variant population right The sickest by far, of the subpopulations. the sickest by far of the subpopulations They do deserve a better drug, and that 0.41 hazard ratio that we presented on with statistical significance, even more impressive given the fact that less than 10% of our patients on Attruby were a variant patients. they do deserve a better drug and that 0.41 hazard ratio that we presented on with statistical significance even more impressive given the fact that less than 10% of our patients on attruby were a variant patients I think that is the best point estimate, again, with the best statistical significance in the space, and extremely consistent with the binding mode that we've articulated, which is differentiated against tafamidis. i think that is the best point estimate again with the best statistical significance in the space and extremely consistent with the binding mode that we've articulated which is differentiated against tafamidis Those would be, I think, the things that we need to do a better job of driving into the marketplace right now. On a go-forward basis, the two big areas that we're interrogating, number one, are real-world evidence, which you should see by the end of this year, this calendar year. The second is the cardiorenal axis work that we're doing, where we think we have a unique signal that connects, interestingly, to the early onset of activity and could really, I think, change the shape of this marketplace going forward. That's what I'd say on that front. Those would be, I think, the things that we need to do a better job of driving into the marketplace right now. those would be i think the things that we need to do a better job of driving into the marketplace right now On a go-forward basis, the two big areas that we're interrogating, number one, are real-world evidence, which you should see by the end of this year, this calendar year. on a go-forward basis the two big areas that we're interrogating number one are real-world evidence which you should see by the end of this year this calendar year The second is the cardiorenal axis work that we're doing, where we think we have a unique signal that connects, interestingly, to the early onset of activity and could really, I think, change the shape of this marketplace going forward. the second is the cardiorenal axis work that we're doing where we think we have a unique signal that connects interestingly to the early onset of activity and could really i think change the shape of this marketplace going forward That's what I'd say on that front. that's what i'd say on that front

Speaker 7: I have a quick follow-up, more on firm-wide strategy. You guys have talked about the transition towards cash flow generation over the course of a couple of years. Obviously, that happens when you have multiple high-margin, small molecule assets. Can you talk about how you guys think strategically long term about use of cash and where and how to put that incremental free cash flow to work? I'm not saying call for a dividend buyback, et cetera, BD, but just how you guys think about your strategy and where that capital should go in a 2028, 2029, 2030, et cetera, free cash flow generating BridgeBio? I have a quick follow-up, more on firm-wide strategy. i have a quick follow-up more on firm-wide strategy You guys have talked about the transition towards cash flow generation over the course of a couple of years. you guys have talked about the transition towards cash flow generation over the course of a couple of years Obviously, that happens when you have multiple high-margin, small molecule assets. obviously that happens when you have multiple high-margin small molecule assets Can you talk about how you guys think strategically long term about use of cash and where and how to put that incremental free cash flow to work? can you talk about how you guys think strategically long term about use of cash and where and how to put that incremental free cash flow to work I'm not saying call for a dividend buyback, et cetera, BD, but just how you guys think about your strategy and where that capital should go in a 2028, 2029, 2030, et cetera, free cash flow generating BridgeBio? i'm not saying call for a dividend buyback et cetera bd but just how you guys think about your strategy and where that capital should go in a 2028 2029 2030 et cetera free cash flow generating bridgebio

Speaker 9: Totally. Well, I would say at the very highest level, as we've been talking about, I think a little bit more over the last couple of months, we're very pleased with the efficiency of our R&D engine. Efficiency, both in terms of time and cost and obviously, the validity of it as it pertains to probably a technical success. As we talked a little bit about, you know, a few months ago, Manny, I know you and I have connected on this. The pipeline that is attended at Gondola is a wonderful example of the ample substrate available to help patients with genetic disease, and our objective function is to serve as broadly as possible. Totally. totally Well, I would say at the very highest level, as we've been talking about, I think a little bit more over the last couple of months, we're very pleased with the efficiency of our R&D engine. well i would say at the very highest level as we've been talking about i think a little bit more over the last couple of months we're very pleased with the efficiency of our r&d engine Efficiency, both in terms of time and cost and obviously, the validity of it as it pertains to probably a technical success. efficiency both in terms of time and cost and obviously the validity of it as it pertains to probably a technical success As we talked a little bit about, you know, a few months ago, Manny, I know you and I have connected on this. as we talked a little bit about you know a few months ago manny i know you and i have connected on this The pipeline that is attended at Gondola is a wonderful example of the ample substrate available to help patients with genetic disease, and our objective function is to serve as broadly as possible. the pipeline that is attended at gondola is a wonderful example of the ample substrate available to help patients with genetic disease and our objective function is to serve as broadly as possible Given all of those things, with cash flow, we would intend, as long as we can beat our cost of capital, to continue to reinvest into R&D and in some cases bring in partially owned assets that we have access to, through Gondola and bring those forward into the, again, highly efficient operating model that we've established in mid to late stage development and ultimately in the, in the commercial setting. Obviously, you know, the stock's not trading where we would like it to trade, and it's trading quite a, quite a ways off intrinsic value. There are opportunities to do other things with cash flows, namely share buybacks and dividends, if indeed, we don't feel we can capture the NPV of fully financed assets, as they move into the marketplace. Given all of those things, with cash flow, we would intend, as long as we can beat our cost of capital, to continue to reinvest into R&D and in some cases bring in partially owned assets that we have access to, through Gondola and bring those forward into the, again, highly efficient operating model that we've established in mid to late stage development and ultimately in the, in the commercial setting. given all of those things with cash flow we would intend as long as we can beat our cost of capital to continue to reinvest into r&d and in some cases bring in partially owned assets that we have access to through gondola and bring those forward into the again highly efficient operating model that we've established in mid to late stage development and ultimately in the in the commercial setting Obviously, you know, the stock's not trading where we would like it to trade, and it's trading quite a, quite a ways off intrinsic value. obviously you know the stock's not trading where we would like it to trade and it's trading quite a quite a ways off intrinsic value There are opportunities to do other things with cash flows, namely share buybacks and dividends, if indeed, we don't feel we can capture the NPV of fully financed assets, as they move into the marketplace. there are opportunities to do other things with cash flows namely share buybacks and dividends if indeed we don't feel we can capture the npv of fully financed assets as they move into the marketplace A bit of this will be just to see whether or not we can do a better job of helping investors avail of the value that we create, and getting the stock price and cost of capital back up into a normal realm. That, I hope, would, you know, sort of get us going in terms of growth in the R&D, in the R&D sector. Does that answer your question? A bit of this will be just to see whether or not we can do a better job of helping investors avail of the value that we create, and getting the stock price and cost of capital back up into a normal realm. a bit of this will be just to see whether or not we can do a better job of helping investors avail of the value that we create and getting the stock price and cost of capital back up into a normal realm That, I hope, would, you know, sort of get us going in terms of growth in the R&D, in the R&D sector. that i hope would you know sort of get us going in terms of growth in the r&d in the r&d sector Does that answer your question? does that answer your question

Speaker 7: Thank you. Absolutely. Congrats again on a good quarter. Thank you. thank you Absolutely. absolutely Congrats again on a good quarter. congrats again on a good quarter

Speaker 9: Thanks, Mani. Thanks, Mani. thanks mani

Speaker 10: Your next question comes from the line of Tyler Van Buren from TD Cowen. Your line is live. Your next question comes from the line of Tyler Van Buren from TD Cowen. your next question comes from the line of tyler van buren from td cowen Your line is live. your line is live

Speaker 12: Hey, guys, thanks for taking the question. Following the three successful phase III in recent months, can you elaborate on your launch readiness and expected field footprint in the context of your burn commentary and the expected cadence of regulatory and commercial catalysts over the next 12 to 18 months? Hey, guys, thanks for taking the question. hey guys thanks for taking the question Following the three successful phase III in recent months, can you elaborate on your launch readiness and expected field footprint in the context of your burn commentary and the expected cadence of regulatory and commercial catalysts over the next 12 to 18 months? following the three successful phase iii in recent months can you elaborate on your launch readiness and expected field footprint in the context of your burn commentary and the expected cadence of regulatory and commercial catalysts over the next 12 to 18 months

Speaker 9: Yeah, thanks, Tyler. Maybe I'll ask Matt and Tom to comment on that. Yeah, thanks, Tyler. yeah thanks tyler Maybe I'll ask Matt and Tom to comment on that. maybe i'll ask matt and tom to comment on that

Speaker 8: Sure. Hey, Tyler. I think, you know, we're going to follow the same rigor as what we did for the Attruby launch. I think one of the big differences is this time we'll be launching on a global basis, and as a part of that, we're building in the U.S., but also ex-U.S. as well. We'll have more on that towards the end of the year in terms of both additional revenue for Attruby that will be coming rest of world, but also our prep and build out for the three additional launches in the U.S. and the rest of the geographies as well. I think what's important, you've seen the recent data readouts. We're setting or resetting the standard of care for each and everyone. Sure. sure Hey, Tyler. hey tyler I think, you know, we're going to follow the same rigor as what we did for the Attruby launch. i think you know we're going to follow the same rigor as what we did for the attruby launch I think one of the big differences is this time we'll be launching on a global basis, and as a part of that, we're building in the U.S., but also ex-U.S. as well. i think one of the big differences is this time we'll be launching on a global basis and as a part of that we're building in the u.s but also ex-u.s as well We'll have more on that towards the end of the year in terms of both additional revenue for Attruby that will be coming rest of world, but also our prep and build out for the three additional launches in the U.S. and the rest of the geographies as well. we'll have more on that towards the end of the year in terms of both additional revenue for attruby that will be coming rest of world but also our prep and build out for the three additional launches in the u.s and the rest of the geographies as well I think what's important, you've seen the recent data readouts. i think what's important you've seen the recent data readouts We're setting or resetting the standard of care for each and everyone. we're setting or resetting the standard of care for each and everyone For LGMD2I and ADH1, it's going to be a first and best-in-class story, and for achon, it's going to be resetting the standard with best-in-class data. For LGMD2I and ADH1, it's going to be a first and best-in-class story, and for achon, it's going to be resetting the standard with best-in-class data. for lgmd2i and adh1 it's going to be a first and best-in-class story and for achon it's going to be resetting the standard with best-in-class data

Speaker 11: I'll take the question on burn. As we've discussed, we've seen over the last several quarters, our cash burn has been on a downward trajectory. That's driven first and foremost by the strong ramp of Attruby and gross profit that it provides. I would also say that it's been due to our disciplined OpEx profile here. As we look to ramp the next three launches, we do expect a gradual increase in OpEx throughout the year. However, we expect burn to hold steady throughout most of the year and drop off again towards the end of the year, as we continue to see an expanding operating margin provided by the Attruby brand. Thanks for the question, Tyler. I'll take the question on burn. i'll take the question on burn As we've discussed, we've seen over the last several quarters, our cash burn has been on a downward trajectory. as we've discussed we've seen over the last several quarters our cash burn has been on a downward trajectory That's driven first and foremost by the strong ramp of Attruby and gross profit that it provides. that's driven first and foremost by the strong ramp of attruby and gross profit that it provides I would also say that it's been due to our disciplined OpEx profile here. i would also say that it's been due to our disciplined opex profile here As we look to ramp the next three launches, we do expect a gradual increase in OpEx throughout the year. as we look to ramp the next three launches we do expect a gradual increase in opex throughout the year However, we expect burn to hold steady throughout most of the year and drop off again towards the end of the year, as we continue to see an expanding operating margin provided by the Attruby brand. however we expect burn to hold steady throughout most of the year and drop off again towards the end of the year as we continue to see an expanding operating margin provided by the attruby brand Thanks for the question, Tyler. thanks for the question tyler

Speaker 10: Your next question comes from the line of Biren Amin from Piper Sandler. Your line is live. Your next question comes from the line of Biren Amin from Piper Sandler. your next question comes from the line of biren amin from piper sandler Your line is live. your line is live

Speaker 3: Hey, hi, guys. Thanks for taking my questions, and congrats on the quarter. I have a high-level question. As you've demonstrated impressive productivity and outlined The BridgeBio Way as a sustainable development model, which was highlighted in the Drug Discovery Today manuscript recently in January. With that in mind, and as we look, you know, beyond 2025, what are the key drivers of momentum for the company, and when should investors expect new assets out of the pipeline? Thank you. Hey, hi, guys. hey hi guys Thanks for taking my questions, and congrats on the quarter. thanks for taking my questions and congrats on the quarter I have a high-level question. i have a high-level question As you've demonstrated impressive productivity and outlined The BridgeBio Way as a sustainable development model, which was highlighted in the Drug Discovery Today manuscript recently in January. as you've demonstrated impressive productivity and outlined the bridgebio way as a sustainable development model which was highlighted in the drug discovery today manuscript recently in january With that in mind, and as we look, you know, beyond 2025, what are the key drivers of momentum for the company, and when should investors expect new assets out of the pipeline? with that in mind and as we look you know beyond 2025 what are the key drivers of momentum for the company and when should investors expect new assets out of the pipeline Thank you. thank you

Speaker 9: Yeah, thanks, Biren. Thanks for the question. you know, a little bit overlapping with some of my comments that I gave against Mani's question as well. Maybe I'll just say, like, near term, our focus continues to be obviously, making sure that these drug products that we just registered successful Phase III on, are approved and ultimately launched correctly. That's the highest and best use of our time right now. The second best use of our time are the additional indications associated with medicines that we know are safe and effective, such as obviously chronic hypopara in the context of encaleret and hypochon and some of the other height disorders that Justin has talked about in the past, associated with infigratinib. Those, that'd be the sort of second category of growth. Yeah, thanks, Biren. yeah thanks biren Thanks for the question. you know, a little bit overlapping with some of my comments that I gave against Mani's question as well. thanks for the question you know a little bit overlapping with some of my comments that i gave against mani's question as well Maybe I'll just say, like, near term, our focus continues to be obviously, making sure that these drug products that we just registered successful Phase III on, are approved and ultimately launched correctly. maybe i'll just say like near term our focus continues to be obviously making sure that these drug products that we just registered successful phase iii on are approved and ultimately launched correctly That's the highest and best use of our time right now. that's the highest and best use of our time right now The second best use of our time are the additional indications associated with medicines that we know are safe and effective, such as obviously chronic hypopara in the context of encaleret and hypochon and some of the other height disorders that Justin has talked about in the past, associated with infigratinib. the second best use of our time are the additional indications associated with medicines that we know are safe and effective such as obviously chronic hypopara in the context of encaleret and hypochon and some of the other height disorders that justin has talked about in the past associated with infigratinib Those, that'd be the sort of second category of growth. those that'd be the sort of second category of growth I think you're asking the right question. Look, at the end of the day, as I mentioned earlier, the scientific substrate available to us to target well-described genetic conditions at their source continues to grow, and we're finding starting points all the way from the clinic, back to, you know, early stage discovery, where we're probably most adept. And that's highlighted in the ever-growing pipeline at Gondola, which obviously BridgeBio shareholders partially own. I would think over the course of time, if indeed we're able to correct our cost of capital and trade closer to intrinsic value, number one, and number two, we're able to really stick the landing and effectively get these drugs approved and launched. I think you're asking the right question. i think you're asking the right question Look, at the end of the day, as I mentioned earlier, the scientific substrate available to us to target well-described genetic conditions at their source continues to grow, and we're finding starting points all the way from the clinic, back to, you know, early stage discovery, where we're probably most adept. look at the end of the day as i mentioned earlier the scientific substrate available to us to target well-described genetic conditions at their source continues to grow and we're finding starting points all the way from the clinic back to you know early stage discovery where we're probably most adept And that's highlighted in the ever-growing pipeline at Gondola, which obviously BridgeBio shareholders partially own. and that's highlighted in the ever-growing pipeline at gondola which obviously bridgebio shareholders partially own I would think over the course of time, if indeed we're able to correct our cost of capital and trade closer to intrinsic value, number one, and number two, we're able to really stick the landing and effectively get these drugs approved and launched. i would think over the course of time if indeed we're able to correct our cost of capital and trade closer to intrinsic value number one and number two we're able to really stick the landing and effectively get these drugs approved and launched There will be a moment where we can bring some of those other assets in and prosecute them with the great infrastructure that we've already set up here, namely, you know, mid- and late-stage development, regulatory, the ability to put it in the hands of a great commercial team, and to do all of that efficiently in terms of time and cost. That, that's kind of the high level answer, I don't have anything specific on a specific asset that we would bring in and like that. I do think you should look for us generally to rely on organic, not inorganic growth. Organic meaning from the ecosystem of BridgeBio activities and BridgeBio companies, and not looking for big M&A or anything like that. There will be a moment where we can bring some of those other assets in and prosecute them with the great infrastructure that we've already set up here, namely, you know, mid- and late-stage development, regulatory, the ability to put it in the hands of a great commercial team, and to do all of that efficiently in terms of time and cost. there will be a moment where we can bring some of those other assets in and prosecute them with the great infrastructure that we've already set up here namely you know mid- and late-stage development regulatory the ability to put it in the hands of a great commercial team and to do all of that efficiently in terms of time and cost That, that's kind of the high level answer, I don't have anything specific on a specific asset that we would bring in and like that. that that's kind of the high level answer i don't have anything specific on a specific asset that we would bring in and like that I do think you should look for us generally to rely on organic, not inorganic growth. i do think you should look for us generally to rely on organic not inorganic growth Organic meaning from the ecosystem of BridgeBio activities and BridgeBio companies, and not looking for big M&A or anything like that. organic meaning from the ecosystem of bridgebio activities and bridgebio companies and not looking for big m&a or anything like that We tend to look at that as a rather expensive mode of growth and one that we probably don't need to take on, given the fact that we're getting to INDs in less than $10 million or $15 million and through Phase I/IIs in less than $100 million. Unless we run out of ideas internally, I don't think we would be aggressively moving toward M&A for growth in the next three to five years. We tend to look at that as a rather expensive mode of growth and one that we probably don't need to take on, given the fact that we're getting to INDs in less than $10 million or $15 million and through Phase I/IIs in less than $100 million. we tend to look at that as a rather expensive mode of growth and one that we probably don't need to take on given the fact that we're getting to inds in less than $10 million or $15 million and through phase i/iis in less than $100 million Unless we run out of ideas internally, I don't think we would be aggressively moving toward M&A for growth in the next three to five years. unless we run out of ideas internally i don't think we would be aggressively moving toward m&a for growth in the next three to five years

Speaker 3: Great. Great. great

Speaker 9: Did I answer your question, Biren? Did I answer your question, Biren? did i answer your question biren

Speaker 3: Yep. Perfect, well. Yep. yep Perfect, well. perfect well

Speaker 10: Your next question comes from the line of Cory Kasimov from Evercore ISI. Your line is live. Your next question comes from the line of Cory Kasimov from Evercore ISI. your next question comes from the line of cory kasimov from evercore isi Your line is live. your line is live

Speaker 1: Hi, this is Adi on for Cory. I wanted to ask on infigratinib. Now, with the phase III data in hand, how are you thinking about the competitive landscape across not just CNP pathway therapies, but also other FGFR-targeted programs, which are more specific to FGFR3? Thank you. Hi, this is Adi on for Cory. hi this is adi on for cory I wanted to ask on infigratinib. i wanted to ask on infigratinib Now, with the phase III data in hand, how are you thinking about the competitive landscape across not just CNP pathway therapies, but also other FGFR- targeted programs, which are more specific to FGFR3? now with the phase iii data in hand how are you thinking about the competitive landscape across not just cnp pathway therapies but also other fgfr- targeted programs which are more specific to fgfr3 Thank you. thank you

Speaker 9: Thanks for the question. Yeah, Justin, you want to take that? Thanks for the question. thanks for the question Yeah, Justin, you want to take that? yeah justin you want to take that

Speaker 6: Yeah. Yeah, thanks for the question. Really, we believe the balance of efficacy and safety shown in PROPEL 3 prove that infigratinib is not just best-in-class, but potentially last-in-class in achondroplasia. Now, on the efficacy side, we had a +2.1 cm per year change from baseline age three, and the first and only stat sig improvement proportionality. Most importantly, we normalize absolute HV, bringing back kids with achondroplasia to wild-type growth levels of 6 cm per year. You know, across every single measure of efficacy, whether it be in animal models or in a clinic, we have set a new bar here. On the safety data side, we had a home run outcome, right? With basically no change in mean phosphate levels between the placebo and treatment arms, and no signs of FGFR1 or 2 associated toxicity. Yeah. yeah Yeah, thanks for the question. yeah thanks for the question Really, we believe the balance of efficacy and safety shown in PROPEL 3 prove that infigratinib is not just best-in-class, but potentially last-in-class in achondroplasia. really we believe the balance of efficacy and safety shown in propel 3 prove that infigratinib is not just best-in-class but potentially last-in-class in achondroplasia Now, on the efficacy side, we had a +2.1 cm per year change from baseline age three, and the first and only stat sig improvement proportionality. now on the efficacy side we had a +2.1 cm per year change from baseline age three and the first and only stat sig improvement proportionality Most importantly, we normalize absolute HV, bringing back kids with achondroplasia to wild-type growth levels of 6 cm per year. most importantly we normalize absolute hv bringing back kids with achondroplasia to wild-type growth levels of 6 cm per year You know, across every single measure of efficacy, whether it be in animal models or in a clinic, we have set a new bar here. you know across every single measure of efficacy whether it be in animal models or in a clinic we have set a new bar here On the safety data side, we had a home run outcome, right? on the safety data side we had a home run outcome right With basically no change in mean phosphate levels between the placebo and treatment arms, and no signs of FGFR1 or 2 associated toxicity. with basically no change in mean phosphate levels between the placebo and treatment arms and no signs of fgfr1 or 2 associated toxicity Really, I think the other molecules being developed in the space, whether it be CNP or FGFR3 inhibitors, have two issues. One, on the efficacy side, you actually don't want to overshoot 6 cm per year too much. We've heard from clinicians that the skeletons and bones in achondroplasia aren't built for too much growth, given preexisting low bone mineral density, and we really hit the sweet spot there. On the safety side, we obviously avoid all the well-known issues associated with the CNP class, such as on vasodilation. Now, the other FGFR3 inhibitors in development trade off selectivity for FGFR1 and 2 for significant VEGFR3 liabilities. There's two issues related to that, and they're not just theoretical risk. The first is on spermatogenesis, and because of this, enrollment in trials are restricted to prepubertal males for these other programs. Really, I think the other molecules being developed in the space, whether it be CNP or FGFR3 inhibitors, have two issues. really i think the other molecules being developed in the space whether it be cnp or fgfr3 inhibitors have two issues One, on the efficacy side, you actually don't want to overshoot 6 cm per year too much. one on the efficacy side you actually don't want to overshoot 6 cm per year too much We've heard from clinicians that the skeletons and bones in achondroplasia aren't built for too much growth, given preexisting low bone mineral density, and we really hit the sweet spot there. we've heard from clinicians that the skeletons and bones in achondroplasia aren't built for too much growth given preexisting low bone mineral density and we really hit the sweet spot there On the safety side, we obviously avoid all the well-known issues associated with the CNP class, such as on vasodilation. on the safety side we obviously avoid all the well-known issues associated with the cnp class such as on vasodilation Now, the other FGFR3 inhibitors in development trade off selectivity for FGFR1 and 2 for significant VEGFR3 liabilities. now the other fgfr3 inhibitors in development trade off selectivity for fgfr1 and 2 for significant vegfr3 liabilities There's two issues related to that, and they're not just theoretical risk. there's two issues related to that and they're not just theoretical risk The first is on spermatogenesis, and because of this, enrollment in trials are restricted to prepubertal males for these other programs. the first is on spermatogenesis and because of this enrollment in trials are restricted to prepubertal males for these other programs The second, and potentially even more overlooked issue, is the effect on angiogenesis. Many molecules that have in-vitro potency findings for VEGFR3, even without clinical findings, end up with a box warning on their labels for impaired wound healing. A great example of this is Retevmo. Net-net, we're really happy with where we've landed on data, and our safety profile obviates the need for other FGFR3 inhibitors. We absolutely could go further in dose given our safety data, but really think that there's no need to in achondroplasia, given that we have gone back to wild-type levels of growth. I hope that answers your question. The second, and potentially even more overlooked issue, is the effect on angiogenesis. the second and potentially even more overlooked issue is the effect on angiogenesis Many molecules that have in- vitro potency findings for VEGFR3, even without clinical findings, end up with a box warning on their labels for impaired wound healing. many molecules that have in- vitro potency findings for vegfr3 even without clinical findings end up with a box warning on their labels for impaired wound healing A great example of this is Retevmo. a great example of this is retevmo Net-net, we're really happy with where we've landed on data, and our safety profile obviates the need for other FGFR3 inhibitors. net-net we're really happy with where we've landed on data and our safety profile obviates the need for other fgfr3 inhibitors We absolutely could go further in dose given our safety data, but really think that there's no need to in achondroplasia, given that we have gone back to wild- type levels of growth. we absolutely could go further in dose given our safety data but really think that there's no need to in achondroplasia given that we have gone back to wild- type levels of growth I hope that answers your question. i hope that answers your question

Speaker 10: Your next question comes from the line of Eliana Merle from Barclays. Your line is live. Your next question comes from the line of Eliana Merle from Barclays. your next question comes from the line of eliana merle from barclays Your line is live. your line is live

Speaker 5: Hey, guys. Thanks for taking the question. Thanks for all the color so far, but, if you could go over your views, in a little bit more depth on the taf IP, and some color there, and specifically your base case for when tafamidis goes generic in the U.S., how you're thinking about it, and can you elaborate on why this doesn't matter for Attruby, in your view? I have a follow-up question. Thanks. Hey, guys. hey guys Thanks for taking the question. thanks for taking the question Thanks for all the color so far, but, if you could go over your views, in a little bit more depth on the taf IP, and some color there, and specifically your base case for when tafamidis goes generic in the U.S., how you're thinking about it, and can you elaborate on why this doesn't matter for Attruby, in your view? thanks for all the color so far but if you could go over your views in a little bit more depth on the taf ip and some color there and specifically your base case for when tafamidis goes generic in the u.s how you're thinking about it and can you elaborate on why this doesn't matter for attruby in your view I have a follow-up question. i have a follow-up question Thanks. thanks

Speaker 9: Hey, Ellie, thanks for the question. Yeah, I mean, you know, broadly, we tend not to comment on the IP situation for our competitors, but obviously it's been a big story for the stock here. Let me turn it over to Chinmay to take a crack, and I'm happy to elaborate on it. Hey, Ellie, thanks for the question. hey ellie thanks for the question Yeah, I mean, you know, broadly, we tend not to comment on the IP situation for our competitors, but obviously it's been a big story for the stock here. yeah i mean you know broadly we tend not to comment on the ip situation for our competitors but obviously it's been a big story for the stock here Let me turn it over to Chinmay to take a crack, and I'm happy to elaborate on it. let me turn it over to chinmay to take a crack and i'm happy to elaborate on it

Speaker 4: Yeah, happy to take that. Ellie, thanks for the question. Maybe I'll talk about it in two ways. I think, as Neil mentioned, we try not to talk about our competitor's IP, especially when the competitor is, you know, not as, we believe, not as potent as our molecule. I think let's talk a little bit about what we think will happen on the trial and maybe a little bit on our strategy for why this doesn't really matter. I think maybe I'll start quickly on Europe, since I know you had some questions there. I think it's important to note that Pfizer, you know, withdrew its patent there, and so that's going to limit the precedential value of this ruling for related parties in other jurisdictions. Yeah, happy to take that. yeah happy to take that Ellie, thanks for the question. ellie thanks for the question Maybe I'll talk about it in two ways. maybe i'll talk about it in two ways I think, as Neil mentioned, we try not to talk about our competitor's IP, especially when the competitor is, you know, not as, we believe, not as potent as our molecule. i think as neil mentioned we try not to talk about our competitor's ip especially when the competitor is you know not as we believe not as potent as our molecule I think let's talk a little bit about what we think will happen on the trial and maybe a little bit on our strategy for why this doesn't really matter. i think let's talk a little bit about what we think will happen on the trial and maybe a little bit on our strategy for why this doesn't really matter I think maybe I'll start quickly on Europe, since I know you had some questions there. i think maybe i'll start quickly on europe since i know you had some questions there I think it's important to note that Pfizer, you know, withdrew its patent there, and so that's going to limit the precedential value of this ruling for related parties in other jurisdictions. i think it's important to note that pfizer you know withdrew its patent there and so that's going to limit the precedential value of this ruling for related parties in other jurisdictions I think as Neil highlighted in his prepared remarks, our base case for Europe has always been entry and, you know, generic entry in 2030 and, you know, that's based on ODE for wild-type ATTR-CM. That's still our assumption. There are two more patents in Europe which protect Pfizer, so there may be some potential upside there. It's also important to note on that front, the really strong treatment, [naive] share that [Brian] has been achieving, you know, which talks a little bit about how physicians, not just in the U.S., but globally, are recognizing the differentiation of acoramidis. Turning to the U.S., which I think is the market, which probably matters a little more, I think Neil had a bunch of comments in his prepared remarks, on how we think about it. I think as Neil highlighted in his prepared remarks, our base case for Europe has always been entry and, you know, generic entry in 2030 and, you know, that's based on ODE for wild-type ATTR-CM. i think as neil highlighted in his prepared remarks our base case for europe has always been entry and you know generic entry in 2030 and you know that's based on ode for wild-type attr-cm That's still our assumption. that's still our assumption There are two more patents in Europe which protect Pfizer, so there may be some potential upside there. there are two more patents in europe which protect pfizer so there may be some potential upside there It's also important to note on that front, the really strong treatment, [naive] share that [Brian] has been achieving, you know, which talks a little bit about how physicians, not just in the U.S., but globally, are recognizing the differentiation of acoramidis. it's also important to note on that front the really strong treatment [naive] share that [brian] has been achieving you know which talks a little bit about how physicians not just in the u.s but globally are recognizing the differentiation of acoramidis Turning to the U.S., which I think is the market, which probably matters a little more, I think Neil had a bunch of comments in his prepared remarks, on how we think about it. turning to the u.s which i think is the market which probably matters a little more i think neil had a bunch of comments in his prepared remarks on how we think about it Based on publicly available information, I think that a couple of things are interesting to note there in addition to what Neil said. One is that Dexcel, which is, I think, the lead filer, has conceded infringement of the 441 polymorph patent. The other interesting thing to note is also that the bar for validity is much more innovator-friendly under U.S. law. As Neil mentioned in his remarks, you know, IP is always uncertain, so we'll keep monitoring it and seeing what happens in Europe in April in the U.S. trials. I think that we feel good about where we are right now, and I think that we do feel like Vyndamax should have protection into the 2030s, potentially up to 2035. Based on publicly available information, I think that a couple of things are interesting to note there in addition to what Neil said. based on publicly available information i think that a couple of things are interesting to note there in addition to what neil said One is that Dexcel, which is, I think, the lead filer, has conceded infringement of the 441 polymorph patent. one is that dexcel which is i think the lead filer has conceded infringement of the 441 polymorph patent The other interesting thing to note is also that the bar for validity is much more innovator-friendly under U.S. law. the other interesting thing to note is also that the bar for validity is much more innovator-friendly under u.s law As Neil mentioned in his remarks, you know, IP is always uncertain, so we'll keep monitoring it and seeing what happens in Europe in April in the U.S. trials. as neil mentioned in his remarks you know ip is always uncertain so we'll keep monitoring it and seeing what happens in europe in april in the u.s trials I think that we feel good about where we are right now, and I think that we do feel like Vyndamax should have protection into the 2030s, potentially up to 2035. i think that we feel good about where we are right now and i think that we do feel like vyndamax should have protection into the 2030s potentially up to 2035 I think it's important to note, though, that we feel like the tafamidis IP debate is a little bit of a sideshow. It doesn't really matter for Attruby's uptake. you know, you guys heard today from Neil and Matt and everyone else about the tremendous momentum which we are seeing for Attruby. You know, the patient weeks, number of patients per week continues to increase as we go forward in our launch and continues to accelerate. I think that's driven by the differentiated clinical data which we have for Attruby. Even in a scenario where a generic tafamidis enters the market, we just don't believe that a less efficacious product will displace a clinically superior therapy in a serious progressive disease. I think it's important to note, though, that we feel like the tafamidis IP debate is a little bit of a sideshow. i think it's important to note though that we feel like the tafamidis ip debate is a little bit of a sideshow It doesn't really matter for Attruby's uptake. you know, you guys heard today from Neil and Matt and everyone else about the tremendous momentum which we are seeing for Attruby. it doesn't really matter for attruby's uptake you know you guys heard today from neil and matt and everyone else about the tremendous momentum which we are seeing for attruby You know, the patient weeks, number of patients per week continues to increase as we go forward in our launch and continues to accelerate. you know the patient weeks number of patients per week continues to increase as we go forward in our launch and continues to accelerate I think that's driven by the differentiated clinical data which we have for Attruby. i think that's driven by the differentiated clinical data which we have for attruby Even in a scenario where a generic tafamidis enters the market, we just don't believe that a less efficacious product will displace a clinically superior therapy in a serious progressive disease. even in a scenario where a generic tafamidis enters the market we just don't believe that a less efficacious product will displace a clinically superior therapy in a serious progressive disease We've seen this pattern, by the way, play out in multiple therapeutic areas such as PH, statins, prostate cancer, where differentiated second to market molecules continue to grow even after the first to market post-generics. We feel good about the long-term value of Attruby, and I think that we look forward to continuing to execute against that. We've seen this pattern, by the way, play out in multiple therapeutic areas such as PH, statins, prostate cancer, where differentiated second to market molecules continue to grow even after the first to market post- generics. we've seen this pattern by the way play out in multiple therapeutic areas such as ph statins prostate cancer where differentiated second to market molecules continue to grow even after the first to market post- generics We feel good about the long-term value of Attruby, and I think that we look forward to continuing to execute against that. we feel good about the long-term value of attruby and i think that we look forward to continuing to execute against that

Speaker 5: Great. Thanks so much. Just a quick follow-up. How do you see the use of serum TTR in clinical practice in the real world evolving and your perspective there, and how that could potentially show differentiation for physicians? Thanks. Great. great Thanks so much. thanks so much Just a quick follow-up. just a quick follow-up How do you see the use of serum TTR in clinical practice in the real world evolving and your perspective there, and how that could potentially show differentiation for physicians? how do you see the use of serum ttr in clinical practice in the real world evolving and your perspective there and how that could potentially show differentiation for physicians Thanks. thanks

Speaker 9: Yeah, great question, Ellie. I'd say first and foremost, you probably saw the recent two JACC papers that came out, you know, looking at serum TTR elevation and correlating it with downstream relative risk of mortality reduction. Both of those were associated with tafamidis, but they reiterated the point that our publication last year made, which is that ever higher levels of serum TTR are associated with ever lower levels of downstream mortality, and that roughly, you could imagine every 1 mg/dL increase, leading to about a 5% relative risk reduction, in downstream mortality. That's exciting. Obviously, the studies that Pfizer did had significantly higher levels of variant patients in them. Yeah, great question, Ellie. yeah great question ellie I'd say first and foremost, you probably saw the recent two JACC papers that came out, you know, looking at serum TTR elevation and correlating it with downstream relative risk of mortality reduction. i'd say first and foremost you probably saw the recent two jacc papers that came out you know looking at serum ttr elevation and correlating it with downstream relative risk of mortality reduction Both of those were associated with tafamidis, but they reiterated the point that our publication last year made, which is that ever higher levels of serum TTR are associated with ever lower levels of downstream mortality, and that roughly, you could imagine every 1 mg/ dL increase, leading to about a 5% relative risk reduction, in downstream mortality. both of those were associated with tafamidis but they reiterated the point that our publication last year made which is that ever higher levels of serum ttr are associated with ever lower levels of downstream mortality and that roughly you could imagine every 1 mg/ dl increase leading to about a 5% relative risk reduction in downstream mortality That's exciting. that's exciting Obviously, the studies that Pfizer did had significantly higher levels of variant patients in them. obviously the studies that pfizer did had significantly higher levels of variant patients in them You're going to see a similar serum TTR rise as you saw in our studies, but that's just basically rigged up so that you can see a higher increase because you've got many more variant patients. If you normalize for variant to wild-type patients, even in cross-trial studies or cross-study comparisons, you can see that we have a significantly higher serum TTR elevation. I think that the most interesting data from that standpoint were literally the same patients going from tafamidis on to acoramidis in the context of our OLE and ATTRibute, where you saw, as I mentioned earlier, that 3 mg/dL increase when going from a partial stabilizer to a full stabilizer. You're going to see a similar serum TTR rise as you saw in our studies, but that's just basically rigged up so that you can see a higher increase because you've got many more variant patients. you're going to see a similar serum ttr rise as you saw in our studies but that's just basically rigged up so that you can see a higher increase because you've got many more variant patients If you normalize for variant to wild- type patients, even in cross-trial studies or cross-study comparisons, you can see that we have a significantly higher serum TTR elevation. if you normalize for variant to wild- type patients even in cross-trial studies or cross-study comparisons you can see that we have a significantly higher serum ttr elevation I think that the most interesting data from that standpoint were literally the same patients going from tafamidis on to acoramidis in the context of our OLE and ATTRibute, where you saw, as I mentioned earlier, that 3 mg/ dL increase when going from a partial stabilizer to a full stabilizer. i think that the most interesting data from that standpoint were literally the same patients going from tafamidis on to acoramidis in the context of our ole and attribute where you saw as i mentioned earlier that 3 mg/ dl increase when going from a partial stabilizer to a full stabilizer I think now we can say, and I remember, Ellie, having this debate with you a long time ago, even just like, what is the shape of that response curve in terms of ever higher levels of stabilization, leading to ever better outcomes? I think here at least we can say it's roughly 5% per mg/dL. You know, it's about a 15% relative risk reduction in terms of mortality going from taf to acoramidis, putting aside the earlier onset of action and some of the other advantages. I think serum TTR will become ever more important, based on these, this bevy of publications. Let's see, it's not, it's not broadly used. I don't know, Matt, if you disagree right now, but I think, you know, our hope is on a go-forward basis, it'll become an ever more important marker of drug action and also therapeutic choice. I think now we can say, and I remember, Ellie, having this debate with you a long time ago, even just like, what is the shape of that response curve in terms of ever higher levels of stabilization, leading to ever better outcomes? i think now we can say and i remember ellie having this debate with you a long time ago even just like what is the shape of that response curve in terms of ever higher levels of stabilization leading to ever better outcomes I think here at least we can say it's roughly 5% per mg/ dL. i think here at least we can say it's roughly 5% per mg/ dl You know, it's about a 15% relative risk reduction in terms of mortality going from taf to acoramidis, putting aside the earlier onset of action and some of the other advantages. you know it's about a 15% relative risk reduction in terms of mortality going from taf to acoramidis putting aside the earlier onset of action and some of the other advantages I think serum TTR will become ever more important, based on these, this bevy of publications. i think serum ttr will become ever more important based on these this bevy of publications Let's see, it's not, it's not broadly used. let's see it's not it's not broadly used I don't know, Matt, if you disagree right now, but I think, you know, our hope is on a go-forward basis, it'll become an ever more important marker of drug action and also therapeutic choice. i don't know matt if you disagree right now but i think you know our hope is on a go-forward basis it'll become an ever more important marker of drug action and also therapeutic choice

Speaker 5: Great. Thanks for the color. Great. great Thanks for the color. thanks for the color

Speaker 9: Yeah. Yeah. yeah

Speaker 4: Thanks, Ellie, for the question. Thanks, Ellie, for the question. thanks ellie for the question

Speaker 10: Your next question comes from the line of Andrew Tsai from Jefferies. Your line is live. Your next question comes from the line of Andrew Tsai from Jefferies. your next question comes from the line of andrew tsai from jefferies Your line is live. your line is live

Speaker 2: Hey, good afternoon. Thanks for taking my question. Just wanted to stick on the theme of cash burn and near-term profitability. What are your guidance expectation on Priority Review Vouchers for non-dilutive capital? I think they're going for $200 million and $300 million apiece right now. Which of your pipeline drugs, or even which indication per drug, could be eligible for PRVs, and when do you expect to receive them? Thank you. Hey, good afternoon. hey good afternoon Thanks for taking my question. thanks for taking my question Just wanted to stick on the theme of cash burn and near-term profitability. just wanted to stick on the theme of cash burn and near-term profitability What are your guidance expectation on Priority Review Vouchers for non-dilutive capital? what are your guidance expectation on priority review vouchers for non-dilutive capital I think they're going for $200 million and $300 million apiece right now. i think they're going for $200 million and $300 million apiece right now Which of your pipeline drugs, or even which indication per drug, could be eligible for PRVs, and when do you expect to receive them? which of your pipeline drugs or even which indication per drug could be eligible for prvs and when do you expect to receive them Thank you. thank you

Speaker 9: Yeah, good question. I didn't factor that into my earlier comments, but, Tom, you want to take that? Yeah, good question. yeah good question I didn't factor that into my earlier comments, but, Tom, you want to take that? i didn't factor that into my earlier comments but tom you want to take that

Speaker 11: Yeah, sure, I'll take that. First, absolutely thrilled to see that program has been reauthorized. It's been a hugely successful incentive for BridgeBio and companies like us in being able to responsibly invest in diseases that affect very few patients and otherwise would be at risk of being left behind. Really happy that that's been extended. We actually have three programs that have already received Rare Pediatric Disease Designation and we expect to be eligible to receive a PRV upon approval. Those are 418 for limb-girdle, infigratinib for achondroplasia, our Canavan gene therapy program. As you rightly pointed out, the pricing of these is not only held in but risen over the last few months. There's significant asset value there already within our portfolio. Yeah, sure, I'll take that. yeah sure i'll take that First, absolutely thrilled to see that program has been reauthorized. first absolutely thrilled to see that program has been reauthorized It's been a hugely successful incentive for BridgeBio and companies like us in being able to responsibly invest in diseases that affect very few patients and otherwise would be at risk of being left behind. it's been a hugely successful incentive for bridgebio and companies like us in being able to responsibly invest in diseases that affect very few patients and otherwise would be at risk of being left behind Really happy that that's been extended. really happy that that's been extended We actually have three programs that have already received Rare Pediatric Disease Designation and we expect to be eligible to receive a PRV upon approval. we actually have three programs that have already received rare pediatric disease designation and we expect to be eligible to receive a prv upon approval Those are 418 for limb-girdle, infigratinib for achondroplasia, our Canavan gene therapy program. those are 418 for limb-girdle infigratinib for achondroplasia our canavan gene therapy program As you rightly pointed out, the pricing of these is not only held in but risen over the last few months. as you rightly pointed out the pricing of these is not only held in but risen over the last few months There's significant asset value there already within our portfolio. there's significant asset value there already within our portfolio Looking out more broadly to the Bridge ecosystem, many of the programs we work on over at Gondola Bio affect children. I would expect there to be many more PRV-eligible programs in the ecosystem around Bridge. Great day for patients and biotech companies like us that are focused on rare disease communities. Looking out more broadly to the Bridge ecosystem, many of the programs we work on over at Gondola Bio affect children. looking out more broadly to the bridge ecosystem many of the programs we work on over at gondola bio affect children I would expect there to be many more PRV-eligible programs in the ecosystem around Bridge. i would expect there to be many more prv-eligible programs in the ecosystem around bridge Great day for patients and biotech companies like us that are focused on rare disease communities. great day for patients and biotech companies like us that are focused on rare disease communities

Speaker 2: Thanks. Thanks. thanks

Speaker 10: That concludes our question and answer session for today. I'll now hand it back over to the company. That concludes our question and answer session for today. that concludes our question and answer session for today I'll now hand it back over to the company. i'll now hand it back over to the company

Speaker 4: Thank you, investors, for joining us on our call today and for the analysts to ask the questions. We look forward to updating you on our next quarterly call in a few months. Thank you. Thank you, investors, for joining us on our call today and for the analysts to ask the questions. thank you investors for joining us on our call today and for the analysts to ask the questions We look forward to updating you on our next quarterly call in a few months. we look forward to updating you on our next quarterly call in a few months Thank you. thank you

Speaker 10: That concludes today's meeting. You may now disconnect. That concludes today's meeting. that concludes today's meeting You may now disconnect. you may now disconnect