BridgeBio Pharma, Inc.

We'll be going live in five, four, three. 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 the number one on your telephone keypad. If you would 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 Bridge Bio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. With that completed, Bridge Bio, you may begin your conference.

Good afternoon, everyone, and thank you for joining BridgeBio Pharma's fourth quarter 2025 earnings call. My name is Chinmay Shukla. I'm the Senior Vice President of Strategic Finance at BridgeBio. With me today are Neil Kumar, our CEO, who will provide opening remarks and discuss overall corporate performance. Matt Outen, our chief commercial officer, who will provide more details about our commercial performance, particularly the continued success of Atruby, and Tom Tremarchi, 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, marked by positive top-line Phase III results for Encallerit in ADH1, BBP418 in LGMD2I, as well as positive top-line data for infagratinib and 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 Anant Sridhar, Anna Wade, and Justin To, who lead Incalerate, BBP418, and Infogratnib, respectively. With that, I'll turn it over to Neil.

Thanks everyone for taking the time today. This is our first earnings call since we reported the results of our phase three study with infogratinib, which delivered a successful outcome for the community we serve in achondroplasia. Altogether with ATTR cardiomyopathy, this brings us to four large post-phase three 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, though, 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 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. 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 Atruby 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 27 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 3 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 three 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 threes, 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 tefamidus 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 infragratinib 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 infogratinib 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'll begin with our recent phase three readout in achondroplasia. As many of you know, we were privileged to generate data alongside the achondroplasia community that suggests a differentiated profile for infragratinib. 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 centimeters per year. In key secondary endpoints, infragratinib 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 8 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 infogratinib. Infogratinib was also well-tolerated with no discontinuations or serious adverse events related to study drug. Three cases or 4% on active of hyperphosphatemia considered 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. As a reminder, infragratinib'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 JP Morgan talk to an excess of 65% peak year share. In addition, that preliminary market research suggests not only differentiated peak year share, but also significant market expansion, similar to what we've seen when orals enter markets as diverse as Fabry, migraine, hereditary angioedema, and in many other categories. In 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. Catherine Matthews from the University of Iowa will give the keynotes. 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, Incalorate, 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 Incalorate and BBP418 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 Atruby net product revenue of $146 million, which corresponded to greater than 25% NBRX share as of December 31st, 2025. Over the last few weeks, Atruby'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're continuing to interrogate the importance of the cardiorenal access, 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 J.P. Morgan, which suggests that binding enthalpy best predicts the conformational stabilization imparted by kinetic stabilizers, as opposed to binding affinity, Kd, or Gibbs free energy. As we have shown through ITC experiments and as we published in Miller et al., we have a vastly superior enthalpic binding mode than does defamitis, which in concert with superior binding kinetics continues to reinforce Atruvi'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 deciliter 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 mg per deciliter when moving from tefamidus to acaramidus. This suggests a whopping 15% relative risk reduction in mortality when moving from tefamidus to acaramidus. Let me also address the recent stock volatility, which is largely centered on questions regarding Vindamax IP and the potential for generic entry. First, it's important to separate two things, the legal process around tefamidus 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 Vindamax equivalent product was unexpected. That said, it did not materially change how we view the EU market given Vindamax's orphan drug exclusivity in wild-type ATTR cardiomyopathy patients. through 2030, which is now and how we have always consistently modeled that geography. In the US, 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 tefamidus IP. Atrubi has demonstrated near-complete stabilization, rapid clinical benefit, and meaningful differentiation in ATTR cardiomyopathy. It is already priced at a discount to Vindamax 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 tofamidus, 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 Atrubi's positioning today and in the years ahead. And with that, I'll turn it over to Matt to speak more specifically about the commercial momentum we're seeing.