BridgeBio (BBIO) Q4 2025 Earnings Call Transcript

Image source: The Motley Fool.

DATE

Tuesday, Feb. 24, 2026, at 4:30 p.m. ET

CALL PARTICIPANTS

• Chief Executive Officer — Neil Kumar
• President and Chief Financial Officer — Thomas Trimarchi
• Chief Commercial Officer — Matthew Outten
• Senior Vice President, Strategic Finance — Chinmay Shukla
• Encaleret Program Lead — Ananth Sridhar
• BBP‑418 Program Lead — Anna Wade
• Infigratinib Program Lead — Justin To

Need a quote from a Motley Fool analyst? Email pr@fool.com

TAKEAWAYS

• Total Revenue -- $154.2 million for the quarter, consisting of $146 million from Atruby net product revenue, $5.3 million from royalty revenue, and $2.9 million from license and service revenue; compared to $5.9 million in total revenue for the same period last year.
• Total Net Product Revenue—Atruby -- $362.4 million for the year and $146 million for the quarter.
• ATRUBY Net Patient Prescriptions -- 7,804 unique patient prescriptions written by 1,856 unique prescribers as of Feb. 20.
• Atruby NBRx Share -- Exceeded 25% as of Dec. 31, 2025; "commercial momentum has continued" into 2026, according to management.
• Q4 QoQ Net Product Revenue Growth -- 35% quarter over quarter for Atruby, per Outten.
• Full Year Revenue -- $502.1 million in 2025, up from $221.9 million in 2024; increase primarily due to Atruby revenue ($359.5 million increase YOY).
• Total Operating Costs and Expenses -- $293.7 million for the quarter; annual total of $1 billion, a $210.6 million annual increase driven by $242.3 million higher SG&A, partially offset by a $54.9 million R&D decrease, mainly from post-approval reductions for Atruby and Biotra.
• Cash Position -- $587.5 million in cash, cash equivalents, and marketable securities at year-end; bolstered by $632.5 million convertible note issue in January 2026.
• Cash Burn -- $446.0 million for the full year; sequentially declining in the quarter, attributed to rising revenues and improved operating leverage.
• Late-Stage Pipeline Profit Projection -- Management projects more than $600 million in profit from four post–Phase 3 assets in 2028, with transition to cash flow generation forecasted to begin in late 2027.
• ATRUBY Clinical Efficacy -- Data cited: "near-complete stabilization, rapid clinical benefit," and a 3 mg/dL increase in serum TTR for patients switching from tafamidis, suggesting a 15% relative risk reduction in mortality at 30 months.
• Market Research—Infigratinib -- Management claims "base case achievable market share" has risen above 65% peak share and references analysis that introduction of an oral expands the market by 170% over five years.
• LGMD2I Readout (BBP‑418) -- Positive top-line Phase 3 data reported; full study dataset to be presented at the Muscular Dystrophy Association Conference; commercial launch readiness in place.
• ADH1 Patient Finding—Encaleret -- 1,700-plus unique patients identified in claims data; supportive pre-NDA communications with the FDA reported.
• Launch Timing Guidance -- Anticipated launches of Encaleret and BBP‑418 set for late 2026 or early 2027.
• PRV Eligibility -- Three programs have Rare Pediatric Disease designation and are expected to be eligible for Priority Review Vouchers: limb-girdle, infigratinib for achondroplasia, and the Canavan gene therapy program.
• Tafamidis IP Position Commentary -- Management states: "our strategy does not depend on tafamidis IP," and regardless of a generic tafamidis scenario, they "do not believe a less efficacious product would undermine the role of a clinically differentiated therapy."
• R&D Efficiency -- Programs advanced from preclinical to Phase 3 at under $300 million, sometimes substantially less, noted as improving probability of technical success versus industry average.

SUMMARY

BridgeBio Pharma (NASDAQ:BBIO) reported a sharp increase in revenue on continued commercial momentum for Atruby, supported by growing prescriber adoption and persistency data. Management highlighted the achievement of three successful late-stage trial readouts, expanding the company's transition potential to a cash-generative multi-product business by 2028. The size and speed of Atruby’s market share gain was attributed to its "near-complete stabilization" profile and rapid onset of action, which are considered key differentiators in treating ATTR cardiomyopathy. Financial discipline was underscored by a declining cash burn trajectory, while new capital secured via 2033 convertible notes extended the operational runway for additional pipeline launches. IP risks surrounding tafamidis were directly addressed, with leadership emphasizing confidence in Atruby’s clinical differentiation and deemphasizing competitive impacts of generic entry.

• Atruby’s clinical mechanism, supported by "superior enthalpic binding mode" and increases in serum TTR, may drive further mortality benefit, as management claims a potential 15% risk reduction when switching from tafamidis.
• Commercial scale-up efforts for LGMD2I and ADH1 were detailed, with new commercial teams onboarded and patient identification progress cited as a foundation for late 2026 to early 2027 launches.
• Company expects the launch of an oral therapy in achondroplasia to significantly expand the market, referencing third-party analysis that predicts up to 170% market growth over five years.
• Pipeline strategy intends to prioritize organic R&D expansion, with capital allocation decisions linked to cost of capital and the ongoing outperformance of the internal discovery engine.
• Expectations for Priority Review Voucher eligibility provide further potential for non-dilutive capital generation as additional rare disease assets approach regulatory approval.

INDUSTRY GLOSSARY

• NBRx: New-to-brand prescription; measures new patients initiated on a specific therapy within a given time period.
• FGFR: Fibroblast Growth Factor Receptor; a target class for pharmaceutical intervention, relevant to achondroplasia and other growth disorders.
• LGMD2I: Limb-Girdle Muscular Dystrophy type 2I, a genetic disorder included in BridgeBio Pharma's development pipeline.
• ADH1: Autosomal Dominant Hypocalcemia Type 1; a rare endocrine disorder targeted by the company's Encaleret program.
• PRV: Priority Review Voucher; a transferable regulatory incentive awarded for the approval of drugs targeting rare pediatric diseases, providing expedited FDA review.
• TTR: Transthyretin; a protein involved in ATTR cardiomyopathy, targeted by BridgeBio Pharma's therapies.
• SG&A: Selling, General, and Administrative expenses; company operating costs excluding R&D and cost of goods sold.

Full Conference Call Transcript

Chinmay Shukla: Good afternoon, everyone, and thank you for joining BridgeBio Pharma, Inc.'s fourth quarter 2025 earnings call. My name is Chinmay Shukla. I am the Senior Vice President of Strategic Finance at BridgeBio Pharma, Inc. With me today are Neil Kumar, our CEO, who will provide opening remarks and discuss overall corporate performance; Matthew Outten, our Chief Commercial Officer, who will provide more details about our commercial performance, particularly the continued success of Atruby; and Thomas Trimarchi, our President and CFO, who will review our financial results. During today's call, we will review our continued strong commercial execution in Atruby'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 Pharma, Inc., marked by positive top-line Phase 3 results for Encalarec NADH1 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 life cycle 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 Encalarec, BBP-418, and infigratinib, respectively.

With that, I will turn it over to Neil. Thanks, everyone, for taking the time today.

Neil Kumar: This is our first earnings call since we reported the results of our Phase 3 study with Infograt, which delivered a successful outcome for the community we serve in achondroplasia. Altogether with ATTR cardiomyopathy, this brings us to four large post–Phase 3 programs, and 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.

But before I get into that, I want to take a moment to paint the picture of what the overall economic productivity of our post–Phase 3 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 $446,000,000 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.

Similarly, 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 Etrubee revenue. That is 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 will distinguish us in the 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 3 assets, which we believe in 2028 will generate more than $600,000,000 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 have been able to advance programs from the preclinical stage through Phase 3 at under $300,000,000, 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 3s 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 have 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 Pharma, Inc. 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 derisking of LGMD2I, our patient finding progress in ADH1, and the clearly differentiated infogratinib readout in achondroplasia, we believe our intrinsic value has increased and its error bars have narrowed.

With over a billion dollars 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 readout. 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 will begin with our recent Phase 3 readout in achondroplasia.

As many of you know, we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile infogratinib. This 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 centimeters per year. In key secondary endpoints, infogratinib also demonstrated the first statistically significant improvement in body proportionality in achondroplasia, with a least squares mean difference of minus 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 prespecified 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 infogradinib. Infogradinib was also well tolerated with no discontinuations or serious adverse events related to study drug. Three cases, or 4% on active, of hyperphosphatemia were mild and transient, with no cases requiring either dose reduction or discontinuation, and no adverse events associated with the inhibition of FGFR1 or FGFR2—for example, retinal or corneal adverse events.

As a reminder, infogratinib’s differentiated oral route of administration and its mechanism, which uniquely targets this well-described condition at its source, produced Phase 2 efficacy and safety results that were highly differentiated. Our Phase 3 data have confirmed those efficacy and safety profiles. And 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 in 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 have seen when orals enter markets as diverse as Fabry, migraine, hereditary angioedema, and in many other categories. In fact, recent analysis done at our Revenue Institute in partnership with MIT suggests that across indications, the launch of an oral product expands the market by approximately 170% over five years from launch of the first oral product. With regards to our efforts in LGMD2I, we are excited to be presenting the full dataset from our study at the upcoming Muscular Dystrophy Association Conference where Doctor Katherine Matthews 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. 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, Encalorate, 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 Encalorate 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 preannounced the fourth quarter Atruvi net product revenue of $146,000,000, which corresponded to greater than 25% NBRx share as of 12/31/2025. Over the last few weeks, Atruby’s commercial momentum has continued. As of February 20, we have seen 7,804 unique patient prescriptions written by 1,856 unique prescribers.

You will 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 Atruby’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/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 3 study that patients increased their serum TTR by 3 mg/dL when moving from tafamidis to acaramidis.

This suggests a whopping 15% relative risk reduction in mortality when moving from tafamidis to acaramidis. Let me also address the recent stock volatility, which is largely centered on questions regarding Vyndamax IP and the potential for generic entry. First, it is important to separate two things: the legal process around tafamidis and the fundamental strength of Atruby. Our confidence in Atruby 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. Atruby 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 cardiomyopathy. In short, we remain confident in Atruby’s positioning today and in the years ahead. I will now turn it over to Matt to speak more specifically about the commercial momentum we are seeing.

Matthew Outten: Thank you, Neil. Consistent with what we highlighted at JPMorgan in January, we believe 2025 reflected strong commercial momentum for Atruby, 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 $502,100,000 in total revenue and $154,200,000 in quarter four. Of this, the net product revenue for Atruby was $362,400,000 and $146,000,000, 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 Atruby 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 Etruebe, 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 at a competitive disadvantage, but our expectations are that Atruby 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 have 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 vutrisiran 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 vutrisiran. The fact that these risks had been omitted but are now stated at the end of each commercial—hopefully all promotional materials and messaging will correct and highlight for patients and healthcare professionals some things to consider with vutrisiran 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 Atruby, there are several driving factors.

First, the number of prescribing HCPs continues to grow, but of equal importance, HCPs who start using Atruby continue using Atruby. 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 Atruvio'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, Atruby has also demonstrated the fastest time to separation to date—a attribute that matters as physicians seek therapies that can deliver meaningful benefit quickly.

Importantly, persistency and adherence for Etrube 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 have continued to build on that foundation with targeted hiring of top talent, including the recent expansion of the Atruvio sales team. Overall, Q4 reflects continued progress across key metrics including growth in patients on therapy and ongoing use by prescribers, and 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 BVP-418, Encalorit, and in fagratinib, 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, bringing much-needed therapies to families and patients in need of care. Building on the successful launch of Etrube, 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.

Thomas Trimarchi: Thank you, Matt, and good afternoon, everyone. I will now discuss our financial results for the fourth quarter and full year 2025. Please note that our commentary on today's call will focus on GAAP financials unless otherwise indicated. Total revenues were $154,200,000 in Q4 2025, consisting of $146,000,000 of Atrivio net product revenue, $5,300,000 of royalty revenue, and $2,900,000 of license and service revenue, compared to total revenues of $5,900,000 for the same period last year.

The $148,300,000 increase in total revenues was primarily driven by a $143,100,000 increase in net product revenue from Atruby, 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 $5,100,000 in royalty revenue from ex-U.S. net sales of BEYONDRA in Europe and Japan. For the full year 2025, total revenues were $502,100,000 compared to $221,900,000 for the full year 2024.

The $280,200,000 increase in total revenues for the full year was primarily due to a $359,500,000 increase in net product revenue for Atruby and an $11,200,000 increase in royalty revenue from sales of Beyond, partially offset by a $90,500,000 decrease in license and service revenues versus the prior year. Total operating costs and expenses for Q4 2025 were $293,700,000 compared to $231,900,000 in the same period in the prior year. The $61,800,000 increase in operating costs and expenses was primarily driven by a $63,300,000 increase in SG&A expenses, partially offset by a $13,900,000 decrease in R&D, primarily due to decreased R&D activities related to Atruvian Biotrio following regulatory approval.

For the full year 2025, total operating costs and expenses were $1,000,000,000 compared to $814,900,000 in the prior year. The $210,600,000 increase was primarily driven by a $242,300,000 increase in SG&A, largely reflecting the company's investments to support the commercial launch and ongoing activities for Atruvio. This increase was partially offset by a $54,900,000 decrease in R&D expenses, primarily due to decreased R&D activities related to Atruvio and Biotra following regulatory approval. Turning to our balance sheet, we ended the year with a cash position of $587,500,000 in cash, cash equivalents, and marketable securities.

We completed the issuance of $632,500,000 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 multiproduct business. With that, I will turn the call back over to Chinmay.

Chinmay Shukla: 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: At this time, I would like to remind everyone, in order to ask a question, press star and the number one on your telephone keypad. Your first question comes from the line of Salim Syed from Mizuho. Your line is live. Hi, guys. This is Bennett for Salim.

Bennett (for Salim Syed, Mizuho): Thanks for taking our question, and congrats on another quarter of continued patient growth. If I may, could you comment on why Atruvio continues to show consistent growth even as competitors' growth seems to be slowing down? Can you comment what are the key drivers behind it? And what is the feedback that you feel is resonating more with docs and patients now that we are several quarters in.

Operator: Thank you.

Neil Kumar: Thanks, Bennett. Maybe I will turn it to Matt to answer that question.

Matthew Outten: Sure. Thanks. I think it is multifaceted, but a big part is the field team that we have at BridgeBio Pharma, Inc. The right team makes or breaks a launch, and that is across both commercial and medical. And then, of course, there is the data. No one has been able to show better data or near-complete stabilization. Only Atruby. I think the time to separation is a big factor, and you heard some of that in the earlier comments. And I think finally, we have stayed disciplined and focused on what is important for patients and HCPs. We have category-leading efficacy and safety with consistent results across all patient types.

So a great team and a great medicine, I think, is hard to slow down.

Neil Kumar: Maybe I will just build on that. 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 is sort of rare if you look and model most launches where you see kind of a burst of activity and then typically you see a slowing. So that really portends one of two things. One is obviously rapid patient identification, which I think we are seeing in the field. And secondly, it is really a second wave of prescribers that are starting to wake up to some of the messages that we are putting forth.

So that, I think, is an exciting profile generally for a launch this early in. And, you know, couple that with nearly 1,200 new scripts since I gave my JPM talk, that is a very, very exciting trajectory right now.

Bennett (for Salim Syed, Mizuho): Alright. Thank you.

Operator: Your next question comes from the line of Mani Foroohar from Leerink Partners. Your line is live. Congrats on continuing to show volume growth.

Mani Foroohar: You have talked a lot about the commercial differentiation and differences in your growth trajectory versus competitors; lots of different pieces of data go into that. But I want to look past out into just what the timeline is into whenever tafamidis and discussed generics and beyond about clinical differentiation, which you have 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 will have significant incremental real-world data, longer-term data, from acaramidis to establish that difference in clinical benefit that you guys are hanging that growth tail on.

Neil Kumar: Great question, Mani. Thanks for it. 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. But as you know from these clinical trials and a lot of the real-world evidence, early CVH is extremely common.

So you want to get patients on the drug that can take action as early as possible. Not only for that reason, but obviously, this is an ongoing mass action in deleterious disease, so you want to be on the drug that has the earliest impact. The second is the AF data that we put forth. Nearly 60% of patients in this space suffer from AF or cardiac arrhythmic events. I think the most important piece of data that we put forth when we showed forth the 70% reduction as published last year is that we are having an equivalent effect on or off AF in the AF subpopulation.

And so, 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 have seen in terms of both reduction in downstream outcomes of 43% and reduction in AF itself of 17%. So 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. And then finally, it is the variant population, the sickest by far of the subpopulations.

They do deserve a better drug, and that 0.41 hazard ratio that we presented with statistical significance is even more impressive given the fact that less than 10% of our patients on ATTRIVUE were 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 have articulated, which is differentiated against tafamidis. So those would be 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 are interrogating, number one, are real-world evidence, which you should see by the end of this calendar year, and the second is the cardiorenal axis work that we are doing. 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. So that is what I would say on that front.

Mani Foroohar: I have a quick follow-up more on firm-wide strategy. You guys have talked about the transition to 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 longer term about use of cash—where and how to put that incremental free cash flow to work? I am not saying call for a dividend, buyback, etc., BD, but how you guys think about your strategy and where that capital should go in a 2028, 2029, 2030, etc., free-cash-flow-generating BridgeBio?

Neil Kumar: Totally. I would say at the very highest level, and as we have been talking about, I think a little bit more over the last couple of months, we are 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 probability of technical success. And as we talked a little bit about a few months ago, Mani, 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.

So given all of those things, with cash flow, we would intend—as long as we could beat our cost of capital—to continue to reinvest into R&D and in some cases in partially owned assets that we have access to through Gondola, and bring those forward into the highly efficient operating model that we have established in mid- to late-stage development and ultimately in the commercial setting. Obviously, the stock is not trading where we would like it to trade, and it is trading quite a ways off intrinsic value.

There are opportunities to do other things with cash flows, namely share buybacks and dividends, if indeed we do not feel we can capture the NPV of fully financed assets as they move into the marketplace. So 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. And then that, we hope, would get us going in terms of growth in the R&D sector. That answer your question?

Mani Foroohar: That is good. Absolutely. And congrats again on a good quarter.

Operator: Thanks, Mani. Your next question comes from the line of Tyler Van Buren from TD Cowen. Your line is live.

Tyler Van Buren: Hey, guys. Thanks for taking the question. So following the three successful Phase 3s 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: Yes. Thanks, Tyler. Maybe I will ask Matt and Tom to comment on that.

Matthew Outten: Sure. Hey, Tyler. I think we are going to follow the same rigor as what we did for the Atruvio launch. I think one of the big differences is this time we will be launching on a global basis. And as a part of that, we are building in the U.S., but also ex-U.S. as well. We will have more on that towards the end of the year, in terms of both additional revenue for Atruvi that will be coming rest of world, but also our prep and buildout for the three additional launches in the U.S. and the rest of the geographies as well. But I think what is important—you have seen the recent data readouts.

We are setting or resetting the standard of care for each and every one. For LGMD2I and ADH1, it is going to be a first- and best-in-class story. And for ACON, it is going to be resetting the standard with best-in-class data.

Thomas Trimarchi: I will take the question on burn. As we have discussed, we have seen over the last several quarters our cash burn has been on a downward trajectory, driven first and foremost by the strong ramp of Atruvi and the gross profit that it provides. But I will also say that it has 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. We continue to see an expanding operating margin provided by the Atruvio brand.

Thanks for the question, Tyler.

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

Biren N. Amin: Congrats on the quarter. I have a high-level question. As you have demonstrated impressive productivity and outlined BridgeBio way as a sustainable development model, which is highlighted in the Drug Discovery Today manuscript recently in January, with that in mind and as we look beyond 2025, what are the key drivers of momentum for the company and when should investors expect new assets under the pipeline?

Neil Kumar: Yes. Thanks, Biren. Thanks for the question. A little bit overlapping with some of my comments against Mani’s question as well. But maybe I will just say, near term, our focus continues to be obviously making sure that these drug products that we just registered successful Phase 3s on are approved and ultimately launched correctly. That is 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 Encalorate, and hypocon and some of the other height disorders that Justin has talked about in the past associated with infigratinib.

So that would be the sort of second category of growth. But I think you are asking the right question. 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 are finding starting points all the way from the clinic back to early-stage discovery where we are probably most adept. And that is highlighted in the ever-growing pipeline at Gondola, which obviously BridgeBio Pharma, Inc. shareholders partially own.

So I would think over the course of time, if indeed we are able to correct our cost of capital and trade closer to intrinsic value, number one, and number two, we are 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 through the great infrastructure that we have already set up here—namely, mid- and late-stage development, regulatory, and the ability to put them in the hands of a great commercial team—to do all of that efficiently in terms of time and cost. That is kind of the high-level answer.

I do not have anything specific on a specific asset that we would bring in 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 do not need to take on given the fact that we are getting to INDs in less than $10 or $15 million and through Phase 1/2s in less than $100,000,000.

So unless we run out of ideas internally, I do not think we would be aggressively moving toward M&A for growth in the next three to five years.

Neil Kumar: Great. Did I answer your question, Biren?

Biren N. Amin: Yep. Definitely.

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

Adi (for Cory Kasimov, Evercore ISI): Hi. This is Adi on for Cory. I wanted to ask on entegraslib. Now with the Phase 3 data in hand, how are you thinking about the competitive landscape across not just the NP pathway therapies, but also other FGFR-targeted programs which are more specific to FGFR3? Thank you.

Neil Kumar: Thanks for the question. Justin, do you want to take it?

Justin To: Yes, again, thanks for the question. We really believe the balance of efficacy and safety shown in BELL3 proved that infigratinib is not just best in class, but potentially last in class in achondroplasia. On the efficacy side, we had a plus 2.1 centimeter per year change from baseline AHV and the first and only statistically significant improvement in proportionality. Most importantly, we normalize absolute AHV, bringing back kids with achondroplasia to wild-type growth levels of 6 centimeters per year. Across every single measure of efficacy, whether it be in animal models or in the clinic, we have set a new bar here.

On the safety side, we had a home-run outcome, with basically no change in mean phosphate levels between the placebo and treatment arms, and no signs of FGFR1 or FGFR2-associated toxicity. Really, I think the other molecules being developed in the space, whether it be CMPs or FGFR3 inhibitors, have two issues. One, on the efficacy side, you actually do not want to overshoot 6 centimeters per year too much. We have heard from clinicians that the skeletons and bones in achondroplasia are not 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 CMP class, such as vasodilation. Now the other FGFR3 inhibitors in development trade off selectivity for FGFR1 and FGFR2 for significant VEGFR3 liabilities. There are two issues related to that, and they are not just theoretical risks. The first is on spermatogenesis, and because of this, enrollment in trials is 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 fruquintinib.

So net-net, we are really happy with where we have 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 we think there is no need to in achondroplasia given that we have gone back to wild-type levels of growth. I hope that answers your question.

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

Eliana Merle: Hey, guys. Thanks for taking the question. Thanks for all the color so far. 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 are thinking about it, and can you elaborate on why this does not matter for Atruby? And then I have a follow-up question. Thanks.

Neil Kumar: Eliana, thanks for the question. We tend not to comment on the IP situation for our competitors, but obviously it has been a big story for the stock here. Let me turn it over to Chinmay to take a crack, and I am happy to elaborate on it.

Chinmay Shukla: Happy to take that. Eliana, thanks for the question. Maybe I will talk about it in two ways. As Neil mentioned, we try not to talk about our competitors’ IP, especially when the competitor is, as we believe, not as potent as our molecule. But I think let us talk a little bit about what we think will happen on the trial and maybe a little bit on strategy for why this does not really matter. I will start quickly on the autops and I know you had some questions there.

It is important to note that Pfizer withdrew its patent there, and so that is going to limit the precedential value of this ruling for related parties in other jurisdictions. As Neil highlighted in his prepared remarks, our base case for Europe has always been generic entry in 2030, and that is based on ODE for wild-type ATTR cardiomyopathy. That is still our assumption. There are two more patents in Europe which protect Pfizer, so there may be some upside there.

It is also important to note on that front the really strong treatment-naïve share that Bayer has been achieving, which talks a little bit about how physicians, not just in the U.S. but globally, are recognizing the differentiation of acaramidis. Turning to the U.S., which I think is the market which probably matters a little more, Neil had a bunch of comments in his prepared remarks on how we think about it. Based on publicly available information, a couple of things are interesting to note there in addition to what he said. One is that Apotex, which I think is the lead filer, has considered infringement of the '441 polymorph patent.

The other interesting thing to note is also that the bar for invalidity is much more in the patentee’s favor under U.S. law. So as Neil mentioned in his remarks, IP is always uncertain, so we will keep monitoring it and seeing what happens in the U.S. trial in April. But we feel good about where we are right now, and we do feel like Vyndamax should have protection into the 2030s, potentially up to 2035. It is important to note, though, that we feel like the tafamidis IP debate is a little bit of a sideshow. It does not really matter for Atruby’s uptake.

You heard today from Neil and Matt and everyone else about the tremendous momentum we are seeing for Atruby. The patient weeks and number of patients per week continue to increase as we go forward in our launch and continue to accelerate. I think that is driven by the differentiated clinical data which we have for Atruby. And so even in a scenario where a generic tafamidis enters the market, we just do not believe that a less efficacious product will displace a clinically superior therapy in a serious, progressive disease.

We have seen this pattern, by the way, play out in multiple therapeutic areas such as PAH, statins, prostate cancer—very differentiated second-to-market molecules continue to grow even after the first-to-market goes generic. So we feel good about the long-term value of Atruby, and we look forward to executing against that.

Eliana Merle: Great. Thanks so much. And just a quick follow-up. How do you see the use of 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: Great question, Eliana. I would say first and foremost, you probably saw the recent two JACC papers that came out 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. So that is exciting.

Obviously, the studies that Pfizer did had significantly higher levels of variant patients in them, so you are going to see similar serum TTR rise as you saw in our studies, but that is just basically rigged up so that you can see a higher increase because you have 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.

But I think the most interesting data from that standpoint were literally the same patients going from tafamidis onto acaramidis 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. And I think now we can say—we were having this debate a long time ago—even just what is the shape of that response curve in terms of ever-higher levels of stabilization leading to ever-better outcomes. And I think here, at least we can say it is roughly 5% per mg/dL.

So it is about a 15% relative risk reduction in terms of mortality going from tafamidis to acaramidis, putting aside the earlier onset of action and some of the other advantages. So I think serum TTR will become ever more important based on this bevy of publications. It is not broadly used right now, but our hope is on a go-forward basis it will become an ever more important marker of drug action and also therapeutic choice.

Eliana Merle: Great. Thanks for the color.

Operator: Thanks, Eliana, for the question. Your next question comes from the line of Andrew Tsai from Jefferies. Your line is live.

Andrew Tsai: Hey. Good afternoon. Thanks for taking my questions. Wanted to stick on the theme of cash burn and near-term profitability. What are your expectations on priority review vouchers for non-dilutive capital? I think they are going for $200 to $300 million apiece right now. So 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: Good question. I did not factor that into my earlier comments. Tom, do you want to take that?

Thomas Trimarchi: Sure. I will take that. First, absolutely thrilled to see that program has been reauthorized. That has been a hugely successful incentive for BridgeBio Pharma, Inc.—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. So really happy that has 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 4-1A for limb-girdle, infigratinib for achondroplasia, and then our Canavan gene therapy program. And as you rightly pointed out, the pricing of these has not only held in but risen in the last few months.

So there is 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, and so there will, I would expect, be many more PRV-eligible programs in the ecosystem around Bridge. So great day for patients and biotech companies like us that are focused on rare disease communities.

Operator: Excellent. That concludes our question-and-answer session for today. I will now hand it back over to the company.

Chinmay Shukla: Thank you, investors, for joining us on our call today and for the analysts who asked the questions. We look forward to updating you on our next quarterly call in a few months. Thank you.

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

This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. Parts of this article were created using Large Language Models (LLMs) based on The Motley Fool's insights and investing approach. It has been reviewed by our AI quality control systems. Since LLMs cannot (currently) own stocks, it has no positions in any of the stocks mentioned. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability.

The Motley Fool recommends BridgeBio Pharma. The Motley Fool has a disclosure policy.