BridgeBio Pharma - Earnings Call - Q2 2025

Transcript

Speaker 5

Good afternoon. I will 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 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 Pharma'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 Pharma's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio Pharma 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 Pharma, you may begin your conference.

Speaker 2

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 Neil Kumar, our CEO, Matt Houghton, our Chief Commercial Officer, and Thomas Trimarchi, our President and Chief Financial Officer. During today's call, we will cover our strong and accelerating launch of Atrubi. We will provide updates on our late-stage pipeline, including the three key phase 3 trials in ADH1, LGMD2i, and achondroplasia. Following our prepared remarks, we will open the call for questions. For the Q&A session, we'll also be joined by Ananth Sridhar, Justin To, and Christine Siu, who lead our phase 3 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 Neil.

Speaker 0

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 Atrubi and as it positions itself for three phase 3 readouts in the coming months across ADH1, LGMD2i, and achondroplasia. The continued star of the show is Atrubi. 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 week-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-CM 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. Of course, all of these numbers connect to the most important set of facts here. First, Atrubi 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. Third, we offer what we feel is a best-in-class clinical and data package in the ATTR-CM space. As discussed before, we have the responsibility to distribute Atrubi as widely as possible so it can be used by any patient that needs it.

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 Atrubi can maximally help specific patient profiles. In any disease category, it is precisely this type of population analysis that allows physicians to deploy the right drug for the right patient. In the case of Atrubi, 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 subpopulations. The first of these publications further strengthens the connection between ever-better stabilization and ever-better clinical outcomes.

Recall that prior to the Atrubi CM study, this connection had already been observed in three ways. First, by looking at the discrepant outcomes between 80 mg tafamidis, which is a 50% stabilizer, and 20 mg diflunisal, which is a 35% stabilizer. Second, by looking at the genotype-phenotype of the disease and the associated rescue mutations. 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 Atrubi 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 Maurer et al.

show in a published paper recently, every 1 mg per deciliter increase in serum TTR leads to a 5% decrease in risk of mortality. Recent work published by authors in Europe, Mannarino et al., also observes this correlation at a quantitative level, and they extend from it a recommendation that serum TTR be used to stage patients with cardiomyopathy. All of this is especially important given that patients who switch from diflunisal to acoramidis, in the context of the Atrubi OLE, all experience significant increases in serum TTR, with an average rise of 3.4 mg per deciliter. Moving to key subpopulation analyses, the first subpopulation we wanted to look at was the variant subtype. As KOLs at the NAC 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, Atrubi 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 Atrubi 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, CVH or ACM, that is associated with a p-value of 0.011. To our knowledge, this is the greatest degree of risk reduction that has 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 outside of our studies in ATTR-CM. Indeed, more than 50% of the population within Atrubi had AFib, allowing us to ask the following questions: Does treatment with Atrubi 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 CVH 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 effects, 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 complemented 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 TTR associated with Atrubi and the three-month separation on CVH and ACM has been demonstrated as a critical aspect of our drug's differentiation. We'll continue to publish on this, Atrubi's rapid action, and we'll have more to say about it at this year's ESC conference.

The sum of this ever-evolving corpus of clinical research, coupled with our efforts in the field, should be increasing scientific share of voice, which in turn should drive treatment-naive share growth, with treatment-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 Atrubi, BridgeBio Pharma is now poised to become a diversified, fully integrated biopharma company with the delivery of up to three novel, best-of-person class assets in high unmet need areas. Each of these high unmet needs represents 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 drive all of the downstream morbidity associated with this condition. BridgeBio Pharma is developing, in its phase 3, 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, easy-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. 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 underdiagnosed condition. Today, we believe that there are some 3,000 diagnosed patients in the U.S. 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 U.S. 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 nonsurgical hyperparathyroidism space have consistently identified, quote, "missing ADH1 patients" to the tune of 20% to 25%. Further, our experience in TTR, where the overall marketplace was also about one-fifth diagnosed, suggests tactics around education and awareness that we believe are applicable to this launch. The results of this phase 3 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 indications for encaleret, specifically in this case in hyperparathyroidism. We plan to present at ASBMR compelling data suggesting the promise of encaleret in chronic hyperparathyroidism. In a cohort of 10 patients, encaleret 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. Third, it might avoid potential downstream bone-associated resorption issues that could require bisphosphonates. Turning now to limb-girdle 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 FARP, salient HP opportunity for encaleret based on data published, and the time value of money.

In summary, BridgeBio Pharma 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, with the capabilities in place across its ecosystem to do even more.

Speaker 1

Thanks, Neil. I'm pleased to report that Atrubi has achieved exceptional performance in the second quarter of 2025, generating $71.5 million in net product revenue, representing 100% growth over quarter one, essentially a doubling of net product revenue. The launch of Atrubi has accelerated with new patient adds now at around 120 patients per week versus 100 patients per week previously. The uptick has been driven by momentum in treatment-naive patients. This strong launch trajectory is driven by more patients starting therapy, along with an increasing number of prescribers choosing Atrubi for their patients. We are operating in a large and fast-growing market. The ATTR-CM category is expanding rapidly and is expected to reach $15 to $20 billion at peak. This strong tailwind provides a significant runway for continued growth and reinforces our conviction in Atrubi becoming a category-defining therapy.

In addition to the significant unmet need in ATTR-CM and the compelling value proposition of Atrubi versus our competitors, our clinical data continues to demonstrate Atrubi's remarkable efficacy. As Neil outlined, we are continuing to generate evidence reinforcing Atrubi's position as a standard of care for ATTR-CM patients, especially in the treatment-naive setting. Let me touch on a few key highlights underlying our commercial performance in the second quarter. Atrubi has a strong and expanding prescriber base. COEs and community HCPs continue to prescribe Atrubi at steady rates, with new prescribers initiating therapy each week. Those who have written in the past continue to do so, and new adopters continue to expand. Atrubi has strong momentum with new starts, capturing share from patients initiating ATTR-CM therapy for the first time and shows strong momentum against peak market share expectations of 30% to 40%.

This is leading to increased demonstrated demand across segments. Fill rates remain robust, well above industry averages, with Atrubi's white-glove patient support programs pulling through the increased prescriptions. Further, days of inventory on hand decline from Q1 to Q2, consistent with increasing familiarity and comfort among specialty pharmacies and distributors with our just-in-time supply model. Why are new prescribers writing, and why do current prescribers write more Atrubi? The number one reason is differentiated efficacy. Atrubi stands out as the only medication with near-complete stabilization in the label, having a near-complete stabilizer and a welcome addition to the market versus a partial stabilizer and a partial knockdown. Beyond choosing efficacy as a primary reason to start Atrubi, HCPs are worried about affordability. Atrubi continues to be the least expensive medication in the ATTR-CM category, with most patients paying $0 out of pocket, reinforcing BridgeBio Pharma's commitment to accessibility.

In fact, in Q2, almost 90% of all Atrubi patients paid $0 for Atrubi. Additionally, we have seen that patients on Atrubi tend to stay on Atrubi and refill prescriptions on time each month. This is likely due to two factors. First, our access and support programs. Our generous assistance programs continue to make Atrubi accessible, seamless, and simple for patients and providers. Secondly, favorable IRA policies have significantly improved out-of-pocket costs for oral medications. ATTR-CM patients are on average on seven to eight other medications, with a typical out-of-pocket for oral drugs being between $0 to $2,000 max annually. This often means that patients add Atrubi for no additional cost, as I had already mentioned. To close, I want to note that the success of this launch reflects our ability to effectively translate strong science into real-world impact and commercial success.

This performance not only reinforces confidence in Atrubi's future but also gives us conviction in our ability to execute future rare disease launches with similar excellence across BridgeBio Pharma's portfolio. As we've discussed, BridgeBio Pharma has three additional potential launches coming over 2026 and 2027. The launch of Atrubi has allowed BridgeBio Pharma to build a strong commercial infrastructure. This includes top industry talent, but also the basis for the programs and launch plans that we'll use to execute these launches. Each of these launches has peak sales potential of more than $1 billion in the U.S. market alone. We look forward to updating you on our commercial readiness in future calls. Now I'll turn it over to discuss our corporate strategy and give an update on our pipeline programs.

Speaker 7

Thank you, Matt, and good afternoon, everyone. I'll now discuss our financial results for the second quarter of 2025. Please note that our commentary in today's call will focus on GAAP financials unless otherwise indicated. Total revenues were $110.6 million in Q2 2025, consisting of Atrubi net product revenue, royalty revenue, and life system services revenue, compared to $2.2 million for the same period last year. The $108.4 million increase in total revenues was primarily due to a $71.5 million increase in net product revenue from our commercial product Atrubi, driven by strong demand across all major prescribers and patient segments. We also recorded $1.6 million in royalty revenue from ex-U.S. net sales of Viagra in Europe and Japan.

Life system services revenue increased by $35.3 million, largely due to the $30 million regulatory milestone recognized under the license agreement of Lexian, final pricing approval of Viagra by the National Health Insurance in Japan in May 2025. Total operating costs and expenses for the second quarter of 2025 were $244.8 million compared to $177.7 million in the same period in the prior year. The $67.1 million increase in operating costs and expenses is primarily driven by a $69.6 million increase in SG&A expenses, partially offset by a $3.5 million decline in R&D expenses. This reflects our continued investment in the Atrubi brand awareness and ongoing investments in our late-stage clinical programs. Included in our total operating costs and expenses was $37.7 million of stock-based compensation expense compared to $21.5 million in the second quarter of 2024.

We expect operating expenses to remain stable through year-end with continued revenue growth driven by Atrubi. Turning to our balance sheet, we ended the second quarter with a strong cash position of $756.9 million in cash, cash equivalents, and marketable securities. This includes proceeds from our strategic modernization of Viagra to European royalties for $300 million, which has significantly strengthened our financial flexibility together with our proceeds from Atrubi sales. Looking ahead, we expect our cash runway to extend through multiple value-creating milestones. In closing, our commercial launch of Atrubi is accelerating, and our pipeline has never been stronger. We look forward to the data-rich months ahead, with top-line results from ADH1 and LGMD2i at the fall 2025 and contemplated in early 2026, and continuing our mission to serve patients and create lasting value for our stakeholders. With that, I'll turn the call back over to Chinmay.

Thank you, Neil, Matt, and To. Operator, please open the line for questions. Thank you.

Speaker 5

Thank you. At this time, I would like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. We ask that you please limit yourself to one question to allow everyone an opportunity to ask a question. We'll go first to Salim Saeed at Mizuho.

Hey, guys. Thanks for the question and congrats on the quarter. I guess one from us on the 120 patient adds per week. Obviously, that's faster than the 109 patient adds if we use the April and February numbers that you guys provided. I'm just curious if you can break that down a little bit more, what you think is driving that patient add number, and specifically, if you can, how you would envision that number changing in the third and fourth quarter of this year. Also, Neil, I don't know if you can comment on this, but I think it's, or Matt, I think it's one of the more important metrics if you can provide it. Just what % of naives coming into the marketplace do you think you got in the second quarter? Thank you.

Speaker 2

Hey, Salim. Thanks for the question. I'm going to pass it on to Matt to talk about the first piece, and then Neil to comment about the second piece.

Speaker 1

Sure. Thanks for the question. I guess to respond to the first half of your question, we're seeing strength in treatment-naive starts and continued switch activity. The market itself is expanding, driven by increased screening and awareness. We're seeing that over a quarter. Unique patient starts and prescriber counts are both increasing. This has resulted in BridgeBio Pharma becoming the partner of choice for healthcare professionals. In addition, the Atrubi profile really resonates. Both patients and doctors are drawn to it. Benefits as soon as three months and a 50% reduction in hospitalization rates. That's across subgroups and across patients switching from other therapies, as Neil mentioned in his opening comments. I think it's a combination of excellent data, an ever-expanding market, and the best team in the industry. Neil, if you want to address the second part.

Speaker 0

Yeah, it's hard to tell, Salim, exactly what the MVRF share is just because we don't precisely know where the knockdowns stand in terms of that. You know, best guess, it's somewhere in the 18% to 20% range, and it's been growing pretty healthily. Just to add to Matt's point, I mean, I think just from being out in the field, a couple of things are starting to drive, I would say, our commercial momentum. The first is better and better access. The second, I think, critically, is increasing scientific share of voice. I think that serum TTR paper actually did a lot of work for us this quarter, and we can build on that. The fact that ever-increasing amounts of stabilization, or in this case, with every additional mg per deciliter increase in serum TTR, you're getting that 5% decrease in mortality.

The fact that that just got confirmed by a European group, I think two days ago, the Mannarini paper came out as well. That's starting to become a really salient feature of both staging patients and deciding which therapy to put them on. I think that coupled with the variant data and coupled with the AFib data, that'll continue to drive momentum here. We just got to continue to educate.

Speaker 5

We'll move next to Tyler Van Buren at TD Cowen.

Hey, guys. Thanks and congratulations on the progress. Last quarter, you all noted the lower than expected utilization of the 28-day free trial and the patient assistance programs. Gross to net modestly boosted net revenue per patient. Could you discuss those three components and how the trends evolved in the second quarter compared to the first quarter, and how you expect them to trend moving forward as we head into the second half of the year?

Speaker 2

Hey, Tyler. Thanks for the question. We did indeed see normalization on all of those three fronts, the 28-day free trial, the back utilization, and the gross to net. Let me turn it over to Neil to give more commentary on what we saw and what we expect to see going forward.

Speaker 0

Yeah, I don't have much to add, as Chinmay said. We did see normalization there. Maybe I'll talk a little bit about why this is so important to us. Obviously, with the variant data, the highest risk reduction shown in the V122i population and the broad variant population. We'll have another publication out on that in the coming months, coupled with statistical significance, which is the first we've seen of that. It's really important for us to be able to serve the underpenetrated populations here with ATTR cardiomyopathy. These programs are a really important feature of that. Maybe less important at the COEs, which is probably where we had initial momentum, and much more important as you drive out into the community and drive out into communities that have historically been underserved.

I'm aware of kind of some of the narrative around, "Oh, man, you guys, you know, look at the L-Nylon launch. It's at double the cost. Like, why didn't you price where you priced? Why didn't you guys have a generous access program and suite, et cetera, et cetera?" Look, I think long term, when you look at any category, I've honestly never seen a drug with better point estimates and a lower price not ultimately do really well in terms of end market share. We're in this for the long game. Honestly, these generous access programs where we price the product, the continued education, and I think the price and these access programs will stand us in good stead long term. I think you should expect to see the GTM stay normalized over the longer course of time and not go back to what we saw initially.

Speaker 5

We'll move next to Biren Amin at Piper Sandler.

Yeah, hi, guys. Thanks for taking my questions. It seems, you know, gross per day in the third quarter accelerated compared to the prior period while you guys face a new competitor. Can you just maybe talk about, you know, community versus academic market share for Atrubi? Maybe a question on the pipeline. What are your thoughts on infigratinib's potential market share in achondroplasia? How are you positioning the hypochondroplasia program given the recent preclinical data? Thanks.

Speaker 2

Hey, Baron. Thank you for your question. I'm going to pass it on to Matt to talk about what's driving the acceleration in the launch and specifically in the treatment-naive segment, both in the COEs and in the community setting. I'll pass it on to Justin to talk about the NC program.

Speaker 1

Yeah. I mean, I think it's the overall data package combined with the unmet need. Patients either are not being treated effectively and are looking for something else. That's one patient profile. There's also patients who are newly diagnosed and are seeking something that can work very fast and hit all the endpoints that they're trying to hit. I think regardless of the type of patients coming in, and then that can be even then split into more subgroups. We have variant populations. You have patients with AFib. Everybody's looking for something that can work quickly and for a long time. I think that is what has gotten us off to such a fast start. The question is, how do you keep that momentum going? The market itself keeps growing every quarter. That's because more and more people now are looking for the disease and finding it.

More patients sort of show up even without us doing anything in that regard. When they do show up and they find the information that we have, whether it's online or from their physician themselves, I think then they're impressed and want to try Atrubi.

Speaker 0

Maybe just to build on that and addressing the specifics that you applied to, it's still a majority in the COE or COE-capitated practices. Recall that 65% of cardiovascular practices are capitated or JV'd in some way with a major provider in their space. We are seeing a pickup in the community. I think that has to do with a lot of the awareness stuff that we and others are doing. It's still a majority in COE or COE-capitated practices, but I expect it'll continue to disperse over time. I don't know. Justin, on this piece?

Speaker 7

Yeah. Infigratinib, just as a reminder, when we started this program, we had two key criteria, right? The first was to have a daily oral treatment option for families who are tired of injections. The second is to have deeper levels of efficacy by not only hitting the MAPK pathway, but also STAT1. Our best-in-class HB data and proportionality data from our phase 2 validates our hypothesis, and most importantly, with the convenience factor of a daily oral. Now, we've consistently done market research that shows an oral with similar efficacy as CMPs would take about 60% of the market in a three-way market. Why? Because clinicians and families all view an oral as better than either a daily or weekly injectable. This market research has been done by others across indications as well, back to data.

We know BioMarin shared some data yesterday on its long-acting CMP, which doesn't change our expectation here. We actually know from their existing phase 2 data that the efficacy on HB and cGMP at 6% plateau above their go-ahead commercial dose. A program that achieves higher levels of CMP here does not really matter. If anything, it makes it even more important to have a therapy that impacts STAT1 since it looks like it affects MAPK down here. Now, on hypochondroplasia, we're really excited about our recent data that we just published in the Journal of Mineral and Bone Research that shows infigratinib has low single-digit in vitro potency against the most common hypochondroplasia mutations and similar efficacy across hypochondroplasia mouse models as it is compared to achondroplasia mouse models. Given that, we expect a similar best-in-class efficacy profile in our hypochondroplasia program as well. More to come there.

Speaker 5

We'll take our next question from Corey Kazimow at Evercore.

Hey, good afternoon, guys. Question for you on encaleret. I'm curious kind of what your market research is suggesting would be considered a meaningful win in the upcoming phase 3 CALIBRATE trial. Thank you.

Speaker 2

Hey, Corey. Thanks for the question. I'm going to pass it on to Ananth, who leads the program, to talk about it.

Speaker 1

Yeah, thanks, Corey. For this program and ADH1 in particular, we see any successful study as a win, really a home run for this community. As we've discussed in the past and as the investor community is familiar, the available conventional therapy or standard of care, to our knowledge, offers pretty meager benefit on the composite endpoint, which we're evaluating in our phase 3, which is concomitant normalization of both blood and urine calcium, which are both important biomarkers in terms of biochemistry for the condition. What we see as a step change for this community is really we can see a majority of patients achieving those criteria on encaleret. We see it as both clinically meaningful and a statistically significant, likely statistically significant benefit achieved for this study and for the patient population.

As a reminder, Corey, if we looked at our phase 2 cohort on these same criteria at the same time point, we saw 9 out of 13, around 69% of our study participants able to achieve that on encaleret. In that same group, none or 0% were able to achieve that criteria on standard of care.

Speaker 5

We'll take our next question from Manny Funrar at Larinc Partners.

Hey, guys. Thanks for taking the question. Congrats on the quarter. I've got a couple, and I'm going to follow Baron's lead by starting on a pipeline and then going to commercial. For LGMD2i, can you lay out, based perhaps on your table conversations and your interactions with the regulators, what the bar is in terms of TFT and biomarker thresholds for potential approval based on the upcoming interim data? I have a commercial question to follow up.

Speaker 2

Sure. I'll pass it on to Christine to talk about LGMD2i.

Speaker 4

Hi, Manny. For the top-line data that we're expecting later this fall, we're going to look for a few different things in the data that would represent a win for us, both in terms of being clinically meaningful as well as supporting a regulatory approval on an accelerated basis. First, we're going to look for a really robust effect on the biomarkers. The primary endpoint is glycosylated alpha disruptant glycan, and what we're hoping to see there would be consistent with our phase 2 results where we saw an elevation in glycosylated alpha disruptant glycan. We think anything 5% or more there would be clinically meaningful. In addition, we're going to look to see a robust reduction in CK of about 40% or more.

On the functional endpoint, what would be considered a win there is a trend in one or more of those outcome measurements. It is important to note that we do not expect full significance at the 12-month time point. The trial was not powered to show it, and the FDA has indicated that it is not a requirement for accelerated approval to see statistical consistency of the clinical outcome. Again, just looking for trends in one or more of the functional outcomes. The third thing we'd like to see is a well-tolerated safety profile consistent with our phase 2 results. I think if we saw all of those, we'd be quite encouraged. Keep in mind, there's really no available treatments today for this indication, so we're pretty excited about the opportunity to have a first-to-market, safe and oral therapy for this indication.

Great. Hopping over to commercial, I guess a little bit of a composite question. LNylon talked a lot about on their call about, you know, adding patient volume for MVUTRA in both switch and new to market therapy patients. Pfizer talked on pricing, how net price had evolved, and they had been doing more contracting to maintain share. For each of these competitors, what are you seeing in terms of impact on your own contracting and pricing? Also, in terms of volume, are you seeing more impact, more impact, and more competitive and sort of more active competition on the switch side? Is it primarily competitive intensity for new to therapy patients? How should we interpret both of those commentaries from those separate calls and how they inform how we think about the competitive dynamic in what is now a multiplayer market?

Speaker 2

Hey, Manny. Thanks for the question. As we noted in our PR, most of our growth came from the treatment-naive section and increasing share there, where we've seen it grow month over month. Let me pass it on to Neil to talk in more detail about these things as he's been out of the field.

Speaker 0

Yeah, thanks, Manny. I mean, I guess I'd say first and foremost, where we're seeing more pressure from the Harvard lockdown is in the switch category, obviously, for us. We were 100% in the switch here prior to, so obviously, you're going to be under pressure there. Recall, there's a couple other modes by which they're getting patients on drug. Initially, one is combination. Actually, hardly, we're seeing a lot of combo when people do reach for the combo. We are seeing people try to use the best stabilizer coupled with the knockdown agents. We've got some combo stuff there, as does, obviously, the boost plus TAV combo. They had the bolus, right? They had their patients that rolled over. We didn't have that because you obviously gave away free drugs for life. They've got what they've got in the naive population.

Honestly, we're not seeing a ton of competition there from Alnylam. We're seeing much more of it from Pfizer. Turning to what Pfizer's doing, we're also not seeing like a ton of race to the bottom, GTN, and contracting type activity in this space. We've made it very clear that we stand on this price. We came in where we came in. We think it's the right thing and the ethical thing for the patient population, but there's not a whole lot of backdoor games that we're playing at all, and we're not seeing it from competition either. Outside of the buy and bill dynamic associated with the knockdowns, we're not seeing a whole lot of competition in that vein. The competition is much more so around clinical differentiation and efficacy. Did that answer your question?

Yeah, thanks. That's really helpful.

Speaker 5

We'll move next to Greg Harrison at Scotia Bank.

Hey, thanks for taking the question and congrats on another quarter of success with the launch and uptake of Atrubi. I wanted to ask, where you have identified areas for growth within the Atrubi launch? Separately, what is BridgeBio Pharma excited about executing on for the remainder of the year?

Speaker 2

Hey, Greg. Thanks for the question. Maybe I'll first pass it on to Neil and then to Matt to talk about what we're excited about in terms of Atrubi and the company. Neil?

Speaker 0

I think as it pertains to Atrubi, I'm excited about a lot of different things, but I'd start with the continued clinical and efficacy differentiation that we've been working on. I really like the way that we've started to port the story from overall, how does this work in the population to specific subpopulations? I think the AFib story or the cardiac arrhythmia story is a really powerful one and certainly opened my eyes to the power of these types of things, be it a variant story, be it a cardiac arrhythmia story, be it someone who has renal involvement story, on and on, etc., etc. I think that's thing number one that gets me excited. Thing number two that gets me excited is the concept of early impact and efficacy.

I think for the longest time, we sort of regarded this as kind of a static picture as soon as things were diagnosed. Obviously, the earlier we go, the better we do in terms of all of the clinical trials. Now we're running this prevention study, and we have drugs that I think leave patients either unprotected for long periods of time, like you see knockdown go from 60% to 82% over the course of 22 months, or you have prompt resolution of destabilization like you do in the case of Atrubi, where you're almost immediately stabilizing that protein and getting the serum TTR levels up by day 28. We look forward to continuing to elaborate on that early action through publications on a go-forward basis. I would say that's one thing. The second thing has to do with access.

Obviously, given the fact that the knockdowns are already there in polyneuropathy, given the fact that TAV is already out there, our new to market EDs are just coming off. We're working really hard with local ISPs to make sure that it's as easy to prescribe Atrubi as it is anything else. We're working with new technologies that allow us to work through forms that are provider-centric, and we're working carefully with Panther and Orsini to have this sort of white-glove service for patients. I think if that revs up over a long period of time, this is going to be a really nice suite of programs and support for patients. I don't know, Matt, if you'd add anything.

Speaker 1

I'd just echo maybe one of the comments that you made. You know, making sure that anyone who wants Atrubi can get it is sort of our primary driver right now. How do we work through any access challenge that might appear? The new to market edits coming off, we've been on the market, I guess, a little over seven months now. Just right in that sweet spot when you start to see all of those things happening, and we are seeing that now. That's going to continue.

We keep talking about how we believe in HCP choice, and I think we've set ourselves up, as you can see from the many programs and different things that we're doing, to try to make sure that it truly is one of those choices and making sure that the physicians have access to the right therapy for each patient without any unnecessary barriers.

Speaker 5

We'll go next to Anupam Rama at JPM.

Hey, guys. Thanks so much for taking the question. For Atrubi, just thinking about prescribing metrics here, it looks like you grew 300+ unique docs quarter over quarter. Just wondering, you know, what's resonating with both new prescribers as well as repeat prescribing dynamics, and where you're seeing the most growth in terms of academic versus community practices. Thanks so much.

Speaker 2

Hey, Anupam. Thank you for the question. I'm going to pass it on to Matt to talk about it.

Speaker 1

Sure. Thanks for the question. First, I think when HCPs try Atrubi and they see how quickly it works, it reinforces the decision that they made to prescribe Atrubi. One prescription just naturally turns to two and so on. Patients and HCPs talk about their experience, not just with a doctor-patient relationship, but also within the patient and physician communities. Their experience with the efficacy of Atrubi, but also with all of our support programs that we've made available, I think has made a tremendous impact. You mentioned community versus COEs, but I think this kind of an impact is equally important in both settings, maybe for potentially different reasons. HCPs who haven't written, they write. They see this, we're out there with our field teams, and they go ahead and make that decision.

Once they've written and those who have written, they continue to write more Atrubi while we do our best to make it easy each and every time. I would expect that you'll see these numbers continue to grow both in the academic and the community centers every quarter.

Speaker 5

We'll take our next question from Paul Choi at Goldman Sachs.

Hi. Good afternoon and congratulations on all the progress. I wanted to turn maybe back to the pipeline for a moment and talk about encaleret and ADH1 and the potential lateral to hypoparathyroidism. Can you maybe speak to your level of conviction as to how success in ADH1 could translate to hypoparathyroidism? Maybe a little more specifically, how you're thinking about responder rates might compare to some of the existing or clinical stage therapies with regard to use of supplements or decreasing use of supplements specifically. Thanks for taking the question.

Speaker 2

Hey, Paul. Thank you for the question. I'm going to pass it on to Ananth to talk about this.

Speaker 1

Sure. Paul, that's a really astute question, especially thinking that ADH1 is the most common genetic subset of hypoparathyroidism. There really is a strong read-through that you're alluding to. A positive study in ADH1 would technically de-risk a lot of the further evaluation that we can and will endeavor to do in chronic hypoparathyroidism broadly. I think the key aspects that I think would be important on the read-through are, one, importantly, a rapid and durable benefit on blood and urine calcium. If we see that in the ADH1 population, it will certainly be encouraging. That is a critical unmet need and a clinical need for the hypoparathyroidism community. The other is going to be on the safety aspect. The broad exposure of the doses we're evaluating in ADH1 will also be an important de-risking signal for the chronic hypoparathyroidism development program.

In terms of the response rates, I'll point the community to our presentation of our sentinel study of encaleret in chronic hypoparathyroidism, which we intend to present at the American Society of Bone Mineral Research meeting, which is taking place next month. In that cohort, we resolved that within five days of dosing initiation with encaleret, 80% of study participants were able to normalize both blood and urine calcium concomitantly. This study did not evaluate whether patients could come off standard of care. That will be evaluated in a longer-term study. Importantly, this is a key differentiating element, which Neil touched on in the earlier remarks, which encaleret could differentiate in this patient population with three critical elements. One, it's oral. Two, it may have a benefit on urine calcium, on 24-hour urinary calcium excretion, to the extent that other therapies have not yet shown to date.

Three, it could avoid long-term bone resorptive effects that may have been seen and may continue to be seen with long-term PTH replacement therapy.

Speaker 5

We will take our final question today from Andrew Sy at Jefferies.

Hey, team. Congrats on the launch execution. Thanks for taking my question. I think one of the thematic discussion points is that Atrubi could be differentiated based on a lot of data you've generated over the past few months. Operationally speaking, how do you exactly leverage the data to convince payers and doctors to use Atrubi more in the first-line setting over the coming years? Can you summarize all the additional data sets that you plan to generate over the next, let's just say, 12 to 24 months? Can we get a glimpse of the real-world data on like NT-proBNP, troponin, all the way to hard outcomes data? Really quickly, can you quantify the inventory changes in Q2 relative to Q1? Thank you.

Speaker 2

Sure. Andy, thank you for your question. I'm going to pass it on to Neil to talk about the Atrubi data. Matt and I can talk a little bit about inventory at the end. Let me pass it on to Neil to talk about the differentiation.

Speaker 0

Yeah, thanks, Andy. I guess your first question was, what are the tactics we're using to educate in and around the data that we have produced? Obviously, there are the obvious aspects of this at conferences, publications, et cetera. I think our Medical Affairs team has done a nice job of increasing our scientific share of voice. Obviously, I think we have the highest velocity of publication in this sector so far. It's given us an opportunity to share something new with the physicians that we do see. The second piece of it, honestly, has been conversations to just say, put some fraction of your patients on Atrubi, to Matt's earlier point, and see what the experience is. I think we feel very comfortable, obviously, with the two real-world evidence studies that have been posted to date out of Dr. Mazari's lab and Dr.

Moore's lab that continued outperformance in the real-world setting. We're doing a lot more of this now on the health economic and real-world setting side. Just what do hospitalizations look like with one stabilizer versus the next? What do overall expenses look like with various SPs, et cetera, et cetera? We're doing a lot of that type of work. I think that's another way that we can allow the data to resonate. A summary of the data, I think of the new data that we just put out has to be the variant data, the 59% relative risk reduction with the STAT6, the AFib data, the 70% reduction along with the 43% reduction in CVH-associated hospitalization. The third, and I think honestly the most important, was the connection once again between ever higher levels of stabilization as measured by serum TTR and better outcomes as measured by mortality.

I think those were the salient data pieces to date. On a go-forward basis, you can expect that we, as I mentioned earlier, are going to publish on all of those fronts plus more. One thing we're definitely going to be looking at is the rapidity of response because I think that now that we've got the PK data from the knockdowns, I think that actually is a huge differentiator of the rapidity of response. You should see a lot more publications coming out on that front. I think the second is the real-world experience with these products, both from the standpoint of biomarkers. I think anti-pro, yes, definitely. I think serum TTR, yes, definitely. Then quality of life and hospitalization measures. Health economic parameters as well. It's interesting, if you go over to Europe, there are countries where we're the only brand.

We won the national bid, and there are major hospitals in areas like Germany where Atrubi is frontline. I think we're sort of looking at those types of very dispassionate, but yet still trying to make a choice between these various data sets, analogs, and saying what really resonated with them in that data and how can we bring some of those messages over to the U.S. market. I don't know, Matt or anyone else, if you'd add anything?

Speaker 1

No, I can touch on the inventory question, though, if that works. I just would make a couple of comments. One, the held inventory is lower in Q2 versus Q1 as suppliers get used to our just-in-time model. You can get Atrubi in less than 48 hours. We talk about that for patients all the time, but it's not just patients. Our suppliers can also get Atrubi in less than 48 hours as well. The sort of old way of doing the supply and demand model, which is, hey, I have to hold multiple weeks of inventory or more because I'm worried about running out or not being able to get some, I think we've sort of changed the game a bit in that. Now that people realize that that's true, they don't have to hold these sort of historical larger levels.

You're seeing that play out in the market now. I think that's just due to the confidence that our distributors have in us.

Speaker 2

Yeah, thanks, Ananth. As Matt said, the days went down because of the accelerating patient demand and the model being more familiar to our suppliers. I appreciate your question.

Speaker 5

That concludes our Q&A for today. I will now hand it back to the company.

Speaker 2

Thank you all for joining us on our Q2 earnings call. We look forward to updating you again in our next earnings call. Thank you. Bye.

Speaker 5

This concludes today's conference. Thank you for your participation. You may now disconnect.