BridgeBio Pharma, Inc.

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 star one again. Thank you. Before we begin, I would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities laws, including but not limited to statements about BridgeBio's future operating and financial performance, business plans and prospects and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward-looking statements. For our discussion of these risks and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law. With that completed, BridgeBio, you may begin your conference.

Good afternoon, everyone, and thank you for joining BridgeBio Pharma's second quarter 2025 earnings call. I'm Chinmay Shukla, Senior Vice President of Strategic Finance at BridgeBio. With me today are Neel Kumar, our CEO, Matt Outen, our Chief Commercial Officer, and Tom Trimarchi, our President and Chief Financial Officer. During today's call, we will cover our strong and accelerating launch of a Truby. We will provide updates on our late-stage pipeline, including the three key phase three trials in ADH1, LGMD2I, and Acon Reclasia. Following our prepared remarks, we will open the call for questions. For the Q&A session, we'll also be joined by Anant Sridhar, Justin Tov, and Christine Shue, who lead our phase three programs. Before we begin, I would like to remind you that this call will include forward-looking statements based on current expectations. These statements represent our judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially. With that, I'll turn it over to Neel.

Thanks to everyone on the line for the time. Welcome to our Q2 earnings call. As always, this is a forum whereby we can communicate to you both on salient results and business strategy. A key aspect of that is ensuring we are communicating the data you feel is important and that we're doing it in a way that's clear. On our last call, we spent a lot of time talking about how we make decisions internally and focused on an NPV-led characterization of our business. Your feedback, which is important, suggested that we spend less time on that and more time on the commercial, medical, and scientific performance of the business. We're excited to do that today because there's much to talk about as the business continues to deliver with the performance of a true beat and as it positions itself for three phase three readouts in the coming months across ADH1, LGMB2I, and achondroplasia. The continued star of the show is a true beat. The first and most important way we've monitored this launch to date is by the number of unique patient prescriptions, which now sits at an absolute number of 3,751, coupled with 1,074 unique prescribers. We're seeing growth in both the number of new prescribers as well as the depth of prescribing at their practices. For those following -by-week status, we've seen over 30% growth in weekly scripts. That acceleration is even greater than our internal projections, given that this was the first full quarter with three players in the ATTR cardiomyopathy market. This prescribing ties to about 100% revenue growth that we've seen in Q2, around $78 million in global sales and 71.5 million in U.S. net sales. And of course, all of these numbers connect to the most important set of facts here. First, a true beat is now positively impacting thousands of patient lives. Second, given the fact that all three bands in this space are growing, we are collectively doing a better job of identifying patients. And third, we offer what we feel is a -in-class clinical and data package in the ATTR cardiomyopathy space. As discussed before, we have the responsibility to distribute a true beat as widely as possible so it can be used by any patient that needs it. And to that end, we continue to have the most generous access programs in this space and are proud that the programs we've pioneered are now being rolled out across the industry to improve access for patients. A second key aspect of our responsibility is to further investigate the existing data and perform novel clinical studies to better understand how a true beat can maximally help specific patient profiles. In any disease category, it is precisely this type of cell population analysis that allows physicians to deploy the right drug for the right patient. In the case of a true beat, over the last quarter, we've published three seminal results, one of which deals with the scientific underpinnings of the disease and two of which touch on important cell populations. The first of these publications further strengthens the connection between ever better stabilization and ever better clinical outcomes. Recall that prior to the attribute CM study, this connection had already been observed in three ways. First, by looking at the discrepant outcomes between 80 mcgaf, which is a 50% stabilizer, and 20 mcgafaminase, which is a 35% stabilizer. Second, by looking at the genotype-phenotype of the disease and the associated rescue mutations. And third, through a small study that had been conducted by academics at BU, suggesting that ever higher tetrameric stabilization as measured by serum TTR levels correlates to better clinical outcomes. A broad analysis of the attribute dataset for the first time isolates the connection between ever higher levels of stabilization as measured by serum TTR levels, which in turn are easily measurable in the clinical context and downstream clinical outcomes in both the wild type and variant context. Importantly, as more at all show in a published paper recently, every one make per deciliter increase in serum TTR leads to a 5% decrease in risk of mortality. Recent work published by authors in Europe, Menervini et al, also observes this correlation at a quantitative level, and they extend from it the recommendation that serum TTR be used to stage patients with cardiomyopathy. All of this is especially important given that patients who switch from defamatous to aparamatous in the context of the attribute OLE all experience significant increases in serum TTR with an average rise of 3.4 makes per deciliter. Moving to key subpopulation analysis, the first subpopulation we wanted to look at was the variant subtype. As KOL's Anac have published, patients with the most common cardiomyopathic variant, D122I, have a 50% probability of survival as compared to even wild type ATTR cardiomyopathy patients. As some of you on the call may remember, aparamatous has a superior binding profile compared to other stabilizers, not only in wild type patients, but also in the variant population, as suggested by two prior publications and reinforced by an upcoming paper that has been submitted for publication that details both biochemical and clinical outcome advantages of Atruby as compared to other stabilizers in the variant population. Once again, we've been able to establish the advantage of that greater stabilization in this subpopulation, and we're able to publish a 59% hazard reduction in time to first event, CBH or ACM, that is associated with a p-value of 0.011. To our knowledge, this is the greatest degree of risk reduction that's been observed in the variant population with the highest degree of statistical significance in the field. Finally, we've published on another important subpopulation, namely patients with cardiac arrhythmic involvement. It turns out that this population is likely more common than certainly I would have thought at the outside of our studies in HDR cardiomyopathy. Indeed, more than 50% of the population within a tribute had AFib allowing us to ask the following questions. Does treatment with Atruby reduce the consequences of AFib, and might it even stave off the occurrence of AFib? It turns out importantly that it is able to do both. We observed a 43% reduction in risk of CBH associated with cardiac arrhythmia, and a 17% reduction in the onset of AFib. Again, we believe this is the best data in the AFib subpopulation published, where other stabilizers appear to have had some effect, and where knockdowns, to our knowledge, based on published AE tables, appear not to have had benefit on AFib occurrence. All of this research is complimented by our ACT Early Trial. In discussions with clinicians and healthcare policy leaders alike, I've been struck by the enthusiasm associated with this courageous trial that seeks to marry what's known about the pathomechanism of this mass action disease, with a bold strategy that extends service to patients beyond the acute phase of disease to potential prevention. What ACT Early reinforces is that the earlier we find patients, and the more quickly we can act on disease, the better off patients are. That's why we also believe that the rapid onset of stabilization and the associated escalation of serum TPR associated with Atruvi, and the three month separation on CVH and ACM as has been demonstrated, is a critical aspect of our drug's differentiation. We'll continue to publish on this, Atruvi's rapid action, and we'll have more to say about it at this year's ESC conference. The sum of this ever evolving focus of clinical research, coupled with our efforts in the field, should be increasing scientific share of boys, which in turn should drive treatment in naive share of growth. With treatment in naive populations being the most important battle we believe to win for patients. Matt will have more to say on the specifics of our launch in some moments. As I mentioned in my opening comments, beyond all of the activity around Atruvi, BridgeBio is now poised to become a diversified, fully integrated biopharma company, with the delivery of up to three novel, best or first in class assets in high unmet need areas. Each of these high unmet needs represent the potential for our drugs to serve additional tens of thousands of patients, and each individually represents billion plus dollar opportunities. Turning to the first of these important readouts in autosomal dominant hypocalcemia type 1, or ADH1. As a reminder, this condition, which has no available pharmaceutical therapies to date, is one that arises uniformly from gain of function mutations in the calcium-sensing receptor, and leads to low serum calcium and high urine calcium levels, which in turn drives all of the downstream morbidity associated with this condition. BridgeBio is developing, in its phase three, a negative allosteric modulator of the calcium-sensing receptor, with the goal to show statistically significant normalization of urinary and serum calcium levels as compared to current standard of care. Given the lack of available pharmaceutical therapy, or really anything reasonable for these patients, our base case expectation for the trial is simply to deliver statistically significant normalization as compared to standard of care, with a safe, -to-take oral drug. The upside expectation, which is certainly consistent with both the biology and what we've seen in the clinic to date, would be response rates at 50% or greater for the patients that we serve. That would be a truly disruptive result. And who are these patients? How many are there? As with many conditions, a lack of pharmaceutical therapy means that this is a poorly characterized and under-diagnosed condition. Today, we believe that there are some 3,000 diagnosed patients in the US alone, but a recent paper we have released, and that's consistent with observations others have made in large genetic databases, indicates that the genetic prevalence is up to 12,000 patients in the US alone. The good news here is that we know where to look to find these patients. As we've discussed before, sequencing efforts in the non-surgical hyperparathyroidism space have consistently identified, quote, missing ADHD1 patients to the tune of 20 to 25%. Further, our experience in TTR, where the overall marketplace was also about 1 fifth diagnosed, suggests tactics around education and awareness that we believe are applicable to this launch. The results of this phase three are anticipated this fall. Importantly, and by the way, this is the case for all of our three late stage medicines, there is substantial promise in follow-on medications for incalorant, specifically in this case, in hyperparathyroidism. We plan to present an ASBMR compelling data suggesting the promise of incalorant in chronic hyperparathyroidism. In a cohort of 10 patients, incalorant normalized urine and serum calcium levels in 80% of patients within five days of dosing. Importantly, this drug brings differentiated promise to the HP community across at least three potential dimensions. First, it's oral. Second, it potentially normalizes urine calcium, the cause of downstream kidney conditions. And third, it might avoid potential downstream bone associated resorption issues that could require bisphosphonates. Turning now to lindneral muscular dystrophy type 2I. This is the second of our first in class products addressed to a deleterious condition that has no available pharmaceutical therapies. Here again, we focused at the intersection of being both safe and highly efficacious. Employing again, a small molecule approach to target this well described condition at its source. This condition uniformly arises from loss of function mutations in an enzyme called FKRP, salient HP opportunity for incalorant based on data published and the time value of money. In summary, BridgeBio stands at the doorstep of transforming itself from a company that is predominantly defined by one asset to a company that is serving a multiplicity of important genetic disease markets. And with the capabilities in place across its ecosystem to do even more.