BridgeBio - Q4 2025

Transcript

Operator (participant)

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.

Chinmay Shukla (SVP of Strategic Finance)

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.

Neil Kumar (CEO)

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.

Matt Outten (Chief Commercial Officer)

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.

Tom Trimarchi (President and CFO)

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.

Chinmay Shukla (SVP of Strategic Finance)

Thank you, Neil, Matt, and Tom. We will now turn the call over to the operator, who will open the line for questions. Thank you.

Operator (participant)

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.

Speaker 12

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.

Neil Kumar (CEO)

Thanks, Bennett. Maybe I'll turn it to, Matt to answer that question.

Matt Outten (Chief Commercial Officer)

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.

Neil Kumar (CEO)

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.

Speaker 12

All right. Thank you.

Operator (participant)

Your next question comes from the line of Mani Foroohar from Leerink Partners. Your line is live.

Mani Foroohar (Senior Managing Director and Biotechnology Analyst)

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?

Neil Kumar (CEO)

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.

Mani Foroohar (Senior Managing Director and Biotechnology Analyst)

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?

Neil Kumar (CEO)

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?

Mani Foroohar (Senior Managing Director and Biotechnology Analyst)

Thank you. Absolutely. Congrats again on a good quarter.

Neil Kumar (CEO)

Thanks, Mani.

Operator (participant)

Your next question comes from the line of Tyler Van Buren from TD Cowen. Your line is live.

Tyler Van Buren (Managing Director and Senior Biotech Equity Research Analyst)

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?

Neil Kumar (CEO)

Yeah, thanks, Tyler. Maybe I'll ask Matt and Tom to comment on that.

Matt Outten (Chief Commercial Officer)

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.

Tom Trimarchi (President and CFO)

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.

Operator (participant)

Your next question comes from the line of Biren Amin from Piper Sandler. Your line is live.

Biren Amin (Managing Director and Investment Analyst in Life Sciences)

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.

Neil Kumar (CEO)

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.

Biren Amin (Managing Director and Investment Analyst in Life Sciences)

Great.

Neil Kumar (CEO)

Did I answer your question, Biren?

Biren Amin (Managing Director and Investment Analyst in Life Sciences)

Yep. Perfect, well.

Operator (participant)

Your next question comes from the line of Cory Kasimov from Evercore ISI. Your line is live.

Adi Jayaraman (Senior Managing Director)

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.

Neil Kumar (CEO)

Thanks for the question. Yeah, Justin, you want to take that?

Justin To (CEO of Skeletal Dysplasias)

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.

Operator (participant)

Your next question comes from the line of Eliana Merle from Barclays. Your line is live.

Eliana Merle (Senior Biotech Equity Research Analyst)

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.

Neil Kumar (CEO)

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.

Chinmay Shukla (SVP of Strategic Finance)

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.

Eliana Merle (Senior Biotech Equity Research Analyst)

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.

Neil Kumar (CEO)

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.

Eliana Merle (Senior Biotech Equity Research Analyst)

Great. Thanks for the color.

Neil Kumar (CEO)

Yeah.

Chinmay Shukla (SVP of Strategic Finance)

Thanks, Ellie, for the question.

Operator (participant)

Your next question comes from the line of Andrew Tsai from Jefferies. Your line is live.

Andrew Tsai (Managing Director)

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.

Neil Kumar (CEO)

Yeah, good question. I didn't factor that into my earlier comments, but, Tom, you want to take that?

Tom Trimarchi (President and CFO)

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.

Andrew Tsai (Managing Director)

Thanks.

Operator (participant)

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

Chinmay Shukla (SVP of Strategic Finance)

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.

Operator (participant)

That concludes today's meeting. You may now disconnect.