Prepared remarks
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. 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 a discussion of these risks and uncertainties, please refer to the disclosures 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 2026 earnings call. I'm Chinmay Shukla, senior vice president, strategic finance. With me today are Neil Kumar, our CEO who will walk through our commercial pipeline and business updates; Matt Outten, our chief commercial officer, who will provide additional detail on Attruby and our launch readiness; and Tom Trimarchi, our president and CFO, who will review our financial results. During today's call, we will cover another quarter of consistent growth for Attruby, along with new data reinforcing its clinical differentiation, including the first evidence of direct kidney protection in ATTR-CM. We will then turn to the pipeline where this quarter all three of our late-stage programs moved from data into being with the FDA, with our first PDUFA date now set for November 27, 2026. And we will review our financial position including the $1 billion preferred equity financing completed on July 1, 2026, and how it supports the three launches ahead of us. Following our prepared remarks, we will open the call for questions. For the Q&A session, we will be joined by Ananth Sridhar, Christine Siu, and Justin To, who lead our programs with encaleret, BBP-418, and infigratinib, respectively. With that, I will turn it over to Neil.
Thanks, Chinmay, and thanks, everyone, for joining today. As always, these calls are where we communicate relevant aspects of our business to investors and so we welcome your questions and feedback. In sessions past, we've had occasion to marry comments on the portfolio with comments regarding financing and strategy. Today, however, I want to focus entirely on the portfolio itself and the progress being made across research, development, and commercial. I'm going to do so because I believe, as I hope you might appreciate at the end of my somewhat lengthy comments, that this is an important transition point for BridgeBio. One in which if we continue executing at a high level, sets us up well for delivering substantial returns for patients and investors alike. Put more simply, it feels like we're at t equals zero in BridgeBio's next chapter. I don't say this glibly, but rather due to the following and overlapping advances. First, as we will discuss, the combination of learnings from CARDIO-TTRansform, our own unique kidney protective data, and extraordinary real-world evidentiary results come together to provide the basis of what I'm calling Launch 2.0 for Attruby. I believe we will start to see significant commercial fruit from this in the six- to nine-month range and beyond judging from analogs. We think the market is shaping up to be a stabilizer-first market with a constrained number of competitors and one in which we have increasing numbers of proof points that our near-complete stabilizer is superior to Pfizer's partial stabilizer. Second, all three NDAs for LGMD2I/R9, ADH1, and achondroplasia have been submitted, with LGMD2I/R9 and ADH1 garnering priority review and we are hoping that achondroplasia might too. Our commercial readiness work is on track, even ahead of what we were able to do for ATTR cardiomyopathy, given our relatively lean resourcing at the time, to deliver strong launches. Third, our chronic hypoparathyroid Phase 3, which we believe is overlooked, has commenced and will read out in the next 18 months, with potential to provide a differentiated efficacy and safety profile, as we will discuss, in addition to being the only oral in this space. Finally, we anticipate novel trials in areas like Turner and hypochondroplasia for infigratinib, a new trial in a to-be-disclosed high-proteinuria orphan kidney disease for acoramidis, and the advancement of a potentially best-in-class TTR antibody into the clinic in the coming 12 to 18 months. All of this activity together provides the substrate for well over $10 billion in risk-adjusted revenue with $8 billion of that being post-Phase 3 today. In addition, our interest in earlier but still advanced genetic medicine R&D within our GondolaBio pipeline continues to bear fruit. So this is a company with no dearth of pragmatic ideas that can drive a continued flux of important medicines on a risk-adjusted basis for the next decade or more to come. I'll begin my portfolio comments with Attruby. First and most importantly, we observed continued commercial momentum this quarter, with Attruby being the fastest growing brand in the space at 23%. And this growth does not account for the impacts of the cardiac, our kidney data, and most of the real-world evidence data to date since those occurred after the quarter end. We've always said that the most important thing commercially and medically in this whole space is diagnosing new patients. To that end, we were heartened to see the substantial overall market growth of 19% this quarter, representing a 51% increase year on year and substantially outstripping the market growth observed in the last three quarters. Consistent with these numbers is the growth in frontline patients, where stabilizers have dominated share, a trend that we think will strengthen as we learn more from CARDIO-TTRansform's important results. Indeed, we observed a slight downtick in numbers of second-line patients in the second quarter. We believe our share in frontline has grown some two to three percentage points although it's hard to tell precisely given some of the inventory dynamics from our competitor, Pfizer. Our gross-to-net also remains within the 30% to 40% that we have indicated previously. Going forward, we expect that the first-line market will continue to grow and we intend to continue growing our share in it, which should translate into continued steady sales growth. Attruby's strongest tailwind, however, is its continually growing clinical differentiation story, driven for the most part by the expanding body of real-world evidence, as well as the now documented renal protective effect. In July of this year, we published in Circulation: Heart Failure that acoramidis is driving the first-ever early and sustained direct kidney protective effects in ATTR cardiomyopathy, including chronic eGFR slope improvement and urinary albumin-to-creatinine ratio reduction. The upshot of this is that Attruby may protect the heart and the kidney simultaneously in ATTR patients, a hemodynamically mediated effect, which we do not observe with other ATTR cardiomyopathy medicines, either knockdowns or other stabilizers. Critically, as pointed out in the paper, the dynamics of this effect mirror the early separation uniquely observed with Attruby in terms of clinical outcomes, helping to explain this early impact. Furthermore, and intriguingly, the magnitude of the acute dip in eGFR on Attruby is actually important and suggestive of downstream benefit. More specifically, comparing acoramidis versus placebo subgroups with acute eGFR dips greater than or equal to the median of 4.89 mL/min/1.73 m² favored acoramidis for all-cause mortality or cardiovascular-related hospitalization, with a whopping hazard ratio of 0.42 with an associated p value of 0.006, and for cardiovascular-related hospitalization alone with a similarly impressive hazard ratio of 0.34 with an associated p value of 0.002. Intriguingly, within the placebo arm, eGFR dips portended worse outcomes. So something initially thought to be a crutch has now been shown to be an important differentiator for our product. The observed effect compares favorably to what we see with other kidney-protective cardiac treatments like SGLT2 inhibitors. In a recently held meeting of nephrologists and cardiologists, one KOL explained to me, 'It looks like we have a kidney drug here.' Building on that, as referred to above, we intend to further interrogate the signal by conducting clinical studies in an orphan kidney indication. More information on that in the weeks to come. Meanwhile, the generation of real-world evidence continues apace. When one looks at analogs in the cardiovascular space, where double-blind head-to-heads were not immediately possible, real-world evidence sets the bedrock of ultimate commercial outperformance. The most storied of these analogs is likely the Eliquis-Xarelto marketplace. Calling back to last quarter, there was an independent propensity-score-matched analysis presented at SCAI, since published, which continues to resonate with physicians. That analysis associated Attruby with a 37% reduction in composite cardiovascular events and a 34% reduction in hospitalizations at six months relative to tafamidis, with an effect deepening at nine months. Remarkably, there was no observed clinical outcome that did not favor Attruby versus Vyndamax; in all measures except for dizziness and syncope, which reached statistical significance of p<0.01 with an n just shy of 600 patients. Building on this data, we have our own now-soon-to-be-published and available-online preprint analysis that, parenthetically, has been downloaded more than 400 times now showing again Attruby outperformance as compared to Vyndamax. Importantly, in this study, a 34% reduction in diuretic intensification, heart failure hospitalization, and mortality was observed, again statistically significant, and separation is again observed as early as 30 days and continues to improve over time. These types of analyses are what the community has been asking for. Importantly, a large-scale independent EHR-based analysis will be coming at HFSA. Our hope is that Attruby continues to perform well there, and that these several RWE studies will form the basis for decision-making and guideline updates. The growing body of research supporting Attruby clinical differentiation will take place alongside evidence from other studies in this rapidly evolving field of ATTR cardiomyopathy. Last month, as you all know, the top-line results for CARDIO-TTRansform studying eplontersen in ATTR cardiomyopathy read out, and the study did not meet the primary efficacy endpoint with no benefit observed with combination therapy. At this point, we mostly want to acknowledge that this is a blow to the patients who participated in the trial and their families and the investigators, and we feel for them as part of the ATTR cardiomyopathy community. The case for combination therapy seems today null from a trial data perspective. Given the similar degrees of knockdown between eplontersen and vutrisiran, we'll be interested to see how the knockdown performs in two settings. Number one, does the monotherapy relative risk reduction continue to underperform what we observed from Attruby at 30 months? And two, does monotherapy knockdown actually not outperform partial stabilizer tafamidis, as we observed in HELIOS-B. Recall, of course, that in addition to the real-world evidence I just cited, everywhere we looked in our ATTRibute-CM trial, acoramidis outperformed tafamidis. The conclusions of this important study run by AstraZeneca and Ionis, we believe, will likely reinforce the case for stabilizers first. And if the monotherapy benefit again lags in time, as observed with vutrisiran in magnitude of effect as compared with Attruby, we believe this begins to make an even stronger case for using Attruby first in the second-line setting. Now I'd like to discuss the three pipeline programs that have moved into regulatory review this quarter and which we are preparing to launch. For BBP-418, our LGMD2I/R9 program, the FDA accepted our NDA on May 27, 2026, with priority review. The PDUFA date is November 27, 2026, and there is no advisory committee planned. We continue to have positive interactions with the agency. This is in line to be the next approval in our portfolio, and it will be the first approved therapy for LGMD2I/R9, a devastating condition affecting a little more than 1,000 patients in the U.S. alone with significant unmet need. There's really no displacing credible competition in this space with gene therapy really the only other pipeline approach, and it suffers from safety and efficacy issues, coupled with the fact that too much FKRP is toxic, so dosing might well be an issue. I'll remind everyone as well that the data generated by our program are easily the most profound ever in the LGMD space and perhaps the broader muscular dystrophy space, given that biochemical improvements tied strongly to functional and statistically significant improvements in ambulation, breathing, and other outcomes, and that the drug promoted improvements as opposed to ever-worsening observations on placebo. From a clinical perspective, our goals are, number one, to educate broadly on already established data and two, to reinforce our observations in the non-ambulatory and severe patient population that may initially be reluctant to try anything. Recall, we observed remarkably consistent benefit in our trial across ages, degree of severity, and the homozygous and compound heterozygous populations. Building on that, we'll be analyzing whether our established functional impacts also marry with some cardiovascular benefit, which affects many patients on the severe end of the spectrum. Our plan is to cut that data and present the results at World Muscle Society in late September/early October, so we are hopeful for a good outcome for the patients we serve there. As we prepare for launch, our neuromuscular commercial and medical field teams are hired, trained, and in the field, and market access is engaging with payers in a pre-approval information exchange. There are approximately 500 genetically confirmed patients today in the United States, with many who remain unidentified and misclassified within the broader LGMD or Becker muscular dystrophy space. Our goal is to find every patient who can benefit and be ready the moment we're able to reach them. Turning to encaleret for ADH1, the FDA accepted our NDA on July 22, 2026, with a PDUFA target action date of May 8, 2027, and no advisory committee planned. At the end of July, the agency granted priority review, and we have announced that today. We have also submitted our MAA to the EMA on July 27, 2026, and it is under review. Encaleret would be the first therapy approved for ADH1 in both the United States and EU, and we are excited to serve this patient population. Speaking of that population, our patient-finding efforts continue, and more than 2,200 patients have been identified in the ICD-10 claims between October 2023 and June 2026. That is an increase of about 300 since the first quarter; it's been driven by genetic testing, awareness education, use of the ICD-10 code, and BridgeBio-supported family testing events. We have also completed enrollment in the first of four cohorts in our pediatric ADH1 study, and are preparing to open cohort two. But ADH1 approval is the beginning of encaleret's potential, not the end. Chronic hypoparathyroidism affects some 200,000 patients in the U.S. and EU, a blockbuster opportunity in and of itself, where, as discussed last quarter, we see a real appetite for an oral option that corrects both hypocalcemia and hypercalciuria. I want to spend a minute on this opportunity because I think it's been significantly overlooked by investors. First, there may be a belief that PTH replacement is the beginning and end of the game here, with advances around dosing, for instance, going from daily to weekly, being the only salient dynamic for patients. But that overlooks a couple of key facts. First, the benefits of existing therapy do not importantly extend to normalization of urine calcium, with some 40% of patients not normalizing and some 50% of chronic hypoparathyroidism patients actually being hypercalciuric. Two, there's a well-documented decrease in efficacy of PTH replacement over time, suggesting that other approaches may be important here. Third, perhaps most importantly, there is a need for a drug that spares the impact of PTH-mediated bone issues, especially considering that in a recent survey of 160 patients, 48% of them had osteoporosis or osteopenia. And fourth, many individuals would prefer an oral medicine. I think some may have discounted this opportunity based on likely probability of technical success. That, I believe, is a mistake. First, the pathomechanism here is well described. Recall first that the hypercalciuria in chronic hypoparathyroidism arises from three independent contributors: one, loss of calcium reabsorption at the distal nephron — that's PTH driven; second, decreased calcium reabsorption in the thick ascending limb — that's calcium-sensing receptor driven; and third, obviously exacerbation by conventional therapy. Analogous to PTH activity in the kidney to mediate reabsorption of calcium, encaleret's action on the calcium-sensing receptor has been shown to increase paracellular reabsorption of calcium in the thick ascending limb by reducing claudin-14 expression, which in turn decreases the amount that integrates into the claudin-16/19 complex which acts as a calciuria-promoting pore-blocking component. This mechanistic rationale helps to explain the observation from our proof-of-concept Phase 2 where 80% of postsurgical hypoparathyroidism patients administered encaleret achieved both normal blood and urine calcium within five days. Okay, so we understand how negative allosteric modulation of the calcium-sensing receptor can mechanistically raise serum and lower urine calcium even in a wild-type setting. But for those of you who don't want to bet on mechanism, recall also there's clinical evidence in the wild-type setting that exists for these drugs, namely the extensive data from the legacy clinical development program of encaleret in osteoporosis participants expressing wild-type calcium-sensing receptor like the chronic hypoparathyroidism population that we intend to study in the RECLAIM-HP trial. And recall that in that osteoporosis study, the drug demonstrated dose-proportional increases in serum calcium at daily doses of 15 mg or above. So we believe, given the endpoints of serum and urine calcium normalization, with all that we've seen and know and the stability of those endpoints statistically, that we have a high probability of technical success trial on our hands. Secondly, investors may believe that the opportunity is not near term. But this is a relatively quick trial given the aforementioned endpoints and the rapidity of onset of our drug. And as mentioned in our press release, we have already activated our first site for the RECLAIM trial, our global Phase 3, have begun screening with first patient in imminent, and a trial readout expected in the next 18 months. Okay. Finally, I'll come to infigratinib, our oral treatment for achondroplasia, where we presented our Phase 3 PROPEL 3 results at the International Congress of Children's Bone Health on June 28 and simultaneously published them in the New England Journal of Medicine — the only achondroplasia program with Phase 3 results in the New England Journal. Following that publication, I'm excited to announce we submitted our NDA, and we are targeting an MAA submission in Q4 of this year. We hope to see NDA acceptance and ideally priority review in Q4 2026 with approval following in mid-2027. Approval would make infigratinib the first FGFR3-targeted oral therapeutic for achondroplasia. And on top of its oral dosing advantage, it remains the only therapy with efficacy measures beyond annualized height velocity demonstrated in a placebo-controlled setting at 52 weeks, including proportionality. Adding to this, we demonstrated a clean functional differentiator in our Phase 3 results with a statistically significant 0.37 standard deviation improvement on arm span with a p value of <0.0001. This is the first-ever placebo-controlled arm span benefit in an achondroplasia trial. We look forward to presenting more data in the second half of this year and continuing to build infigratinib's scientific story through the pre-approval period. On the commercial front, our regional sales directors and medical affairs personnel are onboarded, and the field medical team is fully built. Our RSDs are building teams for meaningful share of voice in a market where two competitors are already present, and where we see a real gap, especially in the U.S., between kids confirmed to have achondroplasia and those on treatment. We continue to think our peak achievable share in this space is above 65%. Finally, I also want to make mention of the critical work occurring off our balance sheet at GondolaBio, where BridgeBio shareholders retain exposure via our ownership stake and ongoing operational support. Our program in EPP announced positive Phase 2a data in June, and following a productive End-of-Phase-2 meeting with the agency, we would be initiating a Phase 2b/3 study in Q3 of this year. Critically, given the over 80% magnitude of PPIX reduction with the quick onset of action and safety profile, the agency suggested that the Phase 2b could form the basis of registration if PPIX lowering was met statistically and other functional trends lined up with it from the point-estimate standpoint. Meanwhile, the rest of the pipeline continues to progress, with some 17 programs and indications including ADPKD, alpha-1 antitrypsin, neurofibromatosis type 1, and CMT1A. In total, the activity has potential to yield five additional INDs by the end of this year, with some eight clinical proof-of-concept readouts to come in the 2027-2028 time frame. Of course, despite all of this, we continue to stay focused on delivering our important medicines to patients in the commercial setting. And for more information on that, I will pass it over to Matt.
Thanks, Neil. Q2 was another strong quarter that demonstrated consistent growth in the treatment-naive segment for Attruby as physicians are increasingly starting and keeping patients on Attruby. Net product revenue was $222.4 million, marking another quarter of $35 million or more of sequential sales increase. I want to spend a moment on the composition of that growth because that is the part that matters most — how we think about the franchise from here. The engine is the first line. Our first-line share stepped up again in Q2 on a first-line market that held roughly steady quarter over quarter and new patient starts were consistent with the first quarter. That is the durable driver of this franchise and it is what we are building against. The second-line or switch segment is behaving differently and I want to be clear about it. The forced Vyndaqel switching that inflated that pool in the fourth and first quarters has now largely been worked through. At roughly 18 months post launch, the switch opportunity is settling into a lower and more normalized steady state. What changed there is the size of the pool, not our performance within it. So the shape of our growth is evolving: continued first-line strength partially offset by a smaller switch market. That is the mix we would expect going forward and it is the mix we are planning around. Neil covered the clinical differentiation data so I want to speak to what it is doing commercially, because this was a meaningful quarter on that front. The endpoints Neil walked through are the ones practicing cardiologists manage week to week, such as hospitalizations, diuretic escalation, and kidney function. And because much of that work was conducted independently of us, it carries the credibility with physicians and with payers that sponsor-generated data does not. We expect additional independent real-world work to read out over the balance of the year. On CARDIO-TTRansform, the outcome was disappointing for patients who had hoped combination therapy would improve on stabilizer monotherapy. What it did do is reinforce stabilization as the first-line standard of care. As the only near-complete stabilizer available, we believe Attruby is well positioned in that setting. That said, the first line remains competitive, and we expect it to stay that way. Our job is to keep earning share on the strength of the data quarter by quarter. Neil noted last quarter that we expected acoramidis to reach block status in 2026, and we remain on track for that. To be precise about what sits inside of that number, we are referring to worldwide sales of acoramidis, which includes BEYONTTRA sales recorded by our partners outside of the United States. It is not a forecast for the U.S. Attruby net product revenue. For the balance of my time, I want to focus on the three approvals ahead of us. The Attruby launch gave us much of the infrastructure any future launch requires, and we have been hard at work making sure each of these goes as well as that one did. These would be the fourth, fifth, and sixth launches in BridgeBio's history. Let me take them in expected order of approval. First, BBP-418. LGMD2I/R9 has never had an approved therapy. Approval would mark the first for LGMD2I/R9 and the first for any form of limb girdle muscular dystrophy. We have submitted a brand name and have conditional acceptance of a proposed proprietary name from the FDA, which we will announce at approval. Our field medical team, sales leadership, and sales team are hired and in field. More than 95% of the sales team has prior neurology experience, with an average of nine years in rare disease. These patients are diagnosed and managed by neurologists and neuromuscular specialists working with a multidisciplinary team so our target universe is concentrated — roughly 700 institutions and 5,300 target specialists with priority reach against approximately 150 parent MDA centers. Ahead of any approval, the team is focused on disease state education and genetic testing awareness, and we continue to build a scalable patient-identification engine that has already identified eligible patients. We are also engaged with payers through pre-approval information exchange, so they understand the value story ahead of the decision, and we will bring the same patient support programs that have supported our prior launches. Second, encaleret in ADH1. At the end of July, the FDA granted priority review for encaleret. The PDUFA target action date is May 8, 2027, and no advisory committee meetings are currently planned. We have built an equally strong field team here with nearly 90% bringing rare disease experience. ADH1 is a genetically distinct condition driven by gain-of-function mutations in the calcium-sensing receptor, which causes low serum calcium, low or inappropriately normal PTH, and a more pronounced increase in urine calcium than hypoparathyroidism generally. Encaleret is designed to target that receptor directly with the potential to address both serum and urine calcium. If approved, it would be the first therapy specifically indicated for adult and adolescent patients with ADH1. As with BBP-418, we are engaged early with payers so that the clinical rationale is well understood before a decision. Third, infigratinib and achondroplasia. We have submitted the NDA, and we anticipate approval in mid-2027. Unlike the other two launches, infigratinib enters the market where competitors are already established. We have delivered against that kind of setup before. What we hear consistently from families, from our HCP and community steering committees, and from market research, is that there is real anticipation for an oral option and awareness of infigratinib is high. The ability to give this medicine as a small once-daily capsule is considerably more than convenience. Aversion to injections is one of the primary barriers keeping families from starting treatment at all, one of the leading reasons they discontinue, and a persistent burden on daily routines and family dynamics. Infigratinib can be swallowed, or the capsule can be twisted open and sprinkled over food. No refrigeration. No reconstitution. No working out how to travel with it. No injection site reactions, and no shots. Families and physicians also see the differentiation as more than the capsule. They consistently point to the efficacy in the PROPEL 3 program, and in particular, the proportionality data in the prespecified 3- to 8-year-old subgroup. Operationally, our commercial infrastructure continues to build. We are being deliberate here because this community is unique and requires a different kind of support when families are weighing whether to start therapy. Our partnership with the achondroplasia community over the past seven years informs how we are approaching this launch. In short, we are on track across all three programs.
Good afternoon, everyone. I'll now walk through our financial results for the second quarter of 2026. Our commentary will focus on GAAP financials unless otherwise noted. Total revenues for the second quarter of 2026 were $243.7 million compared to $110.6 million for the same period in 2025. The $133.1 million increase was primarily driven by a $150.9 million increase in Attruby net product revenue. Attruby net product revenue in the quarter was $222.4 million compared to $71.5 million in the same period last year. Royalty revenue increased $15.4 million compared to $1.6 million in the same period last year, primarily earned from net product sales of BEYONTTRA in the EU and Japan. License and services revenue was $5.8 million compared to $37.4 million in the same period last year, which included a one-time $30 million regulatory milestone recognized under the Alexion agreement following pricing approval in Japan. Total operating expenses for the second quarter of 2026 were $335.7 million compared to $241.2 million for the same period last year. A $94.5 million increase reflects deliberate and disciplined investment in the Attruby preparations for three upcoming launches. It was primarily driven by scale-up of sales, marketing, medical affairs, and pre-commercial product-supply-related activities. Turning to the operating line: in the second quarter, we recorded a $107.1 million loss from operations compared to a $134.3 million loss in the same period last year — an improvement of $27.2 million or approximately 20% year over year. Now on to the balance sheet. As of June 30, 2026, our cash, cash equivalents, and marketable securities were $720.2 million. Subsequent to the quarter end on July 1, 2026, we closed a $1 billion preferred equity investment led by Sixth Street with participation from HealthCare Royalty. Our cash balance was approximately $1.7 billion as of July 1, 2026. We believe our current cash position provides us with significant runway to fund our operating activities, execute on three potential launches over the next 12 months, and continue to invest in Attruby's commercial growth, all while maintaining the financial discipline we have demonstrated to date.
Thank you, Neil, Matt, and Tom. Operator, please open the line for questions now.
Questions and answers
Thank you. We will now begin the question-and-answer session. If you have dialed in and would like to ask a question, please press 1 on your phone. If you would like to withdraw your question, simply press 1 again. We ask that you please limit yourself to one question to allow everyone an opportunity to ask a question. We'll go first to Tyler Van Buren at TD Cowen.
Hey, guys. Good evening, and congratulations on another strong quarter. It's great to see the more than $35 million sequential U.S. revenue that Attruby added again this quarter. But as the release specifically calls out Attruby growth led by the treatment-naive segment as physicians increasingly start and keep patients on Attruby, can you discuss what is driving that consistency in the first line? And perhaps most importantly, given competitive developments, why those drivers are durable? And perhaps could also layer that in with expectations for the potential impact that the CARDIO-TTRansform failure and upcoming data at ESC could have on Attruby's treatment-naive share as well?
I'm sorry. I will pass on to Matt to comment on some of the commercial dynamics, and then I'll pass on to Neil if he wants to add things on CARDIO-TTRansform expectations at ESC.
Okay. Thanks for the question, Tyler. I think there's two interesting components here. There's the reason that Attruby has done so well to date — namely how quickly Attruby separates from placebo along with the incredible reduction in hospitalization rates — and then there's the new data that Neil discussed today. The performance you've seen to date has been rooted in the clinical differentiation story. Now we can add to that with compelling insights from the real-world evidence, kidney data, and CARDIO-TTRansform, and this is going to add on to the earlier messaging and continue to push share forward in the future. I'll let Neil add on with the CARDIO-TTRansform thoughts.
Yeah. Thanks, Tyler. I guess I'd just say, we have to see what the data looks like, but by and large, I would expect that stabilizer frontline will do nothing but gain from the CARDIO-TTRansform dataset, so just be a larger pool. And in that pool, I think, to Matt's point, we'll continue to differentiate and I think we're going to see the fruit that I mentioned in my comments — of the real-world evidence and kidney differentiation — really by about half a year from now or so. If you look at analogs, it generally takes about six to nine months to pull through some of this data. Obviously, also dependent on what HFSA looks like in the independent RWE analysis, but if everything continues to go the way of Attruby — as you start to connect all the dots from biochemistry to serum TTR, a 1 mg/dL is a 5% decrease in mortality risk in 30 months, and all of the real-world evidence against survival — I think we'll see strong results at HFSA. We saw hints of that with independent data around hospitalizations and ODI as we mentioned today. I think all of that comes together to say we have a superior stabilizer, and that's really the message we have to continue to hit. My expectation would be that we hit a positive second derivative here and continue to grow aggressively in the frontline over the coming 12 to 18 months. So let's see.
We'll go next to Cory Kasimov at Evercore ISI.
Hey. Good afternoon. Thanks for taking my question. Perhaps not surprisingly, I also want to ask a question regarding CARDIO-TTRansform missing the primary endpoint. So now, at this point, we obviously know there was substantial background stabilizer use and putting the silencer on top of it didn't improve outcomes. So I know you touched on some of this in your prepared remarks, but in your view, does this not only cement stabilizers as the first-line backbone here in future treatments? But also, do you have any feedback at this point from your KOLs and payer discussions as to how prescribing and reimbursement of any combination therapy may evolve from here? Thank you.
Yeah. Thanks for the question. Maybe I'll start, and Matt can add on. I'd say it's a little early for us to get feedback from payers. On the KOL side, for sure, we've been hearing a bit of surprise, honestly. There are folks that can be convinced with biochemistry and biophysics, but I think a large trial like this convinces a lot of folks and might be changing minds. So I do think stabilizers will be an increasingly large part — they already are a large part — of the frontline, and I think that's where the real action will be in this category. The three things we're looking for with regard to CARDIO-TTRansform: first, eplontersen and vutrisiran have very similar knockdown profiles, so we have to look at pharmacokinetics to see whether eplontersen is slightly superior to vutrisiran because vutrisiran obviously took a long time to get to its mean max knockdown. Second, within the context of the clinical data, what's the 30-month data look like — is anyone getting to 3, 4, 2, 5? How quickly are folks separating in terms of effect? Because I think if you look at the totality of evidence, my suspicion will be that not only do you get the magnitude of relative risk reduction that makes Attruby look superior at 30 months, but if there's no early separation, it really starts to suggest that you ought to be using Attruby in that switch setting just given both its magnitude and the early onset now well described by this kidney data. The second intriguing point will be to see whether monotherapy knockdown actually outperforms a partial stabilizer. People sometimes forget that in HELIOS-B, monotherapy did not significantly outperform tafamidis, which was a bit surprising to me based on the toxic monomer hypothesis until you look at the pharmacokinetics. If eplontersen doesn't outperform a partial stabilizer, recall we've had a stabilizer outperform tafamidis in every single part of the ATTRibute-CM trial we looked at and in all major RWE studies. Again, that begins to establish Attruby as a superior efficacious agent compared to both knockdowns and the partial stabilizer of Pfizer. So these will be the things we are watching closely.
Well said. I think we're interested in seeing the full data set at ESC, but certainly the results don't appear to support combination therapy, which just then reinforces stabilization as the backbone of therapy. Again, on the partial stabilizer versus a near-complete stabilizer, that's kind of where we are, and I don't think anything at ESC is going to change that based on the initial results that were posted.
We'll go next to Eliana Merle at Barclays.
Guys, thanks for taking the question and congrats on all the progress. So the Pfizer release cited net price erosion from new payer contracts, while your gross-to-net has remained stable within the range you guided to. Given Attruby launched at a list price below tafamidis, do you see any need to respond on price, or is clinical differentiation carrying access and share on its own? Thanks.
Yeah. Thanks, Eliana. It's an important question. I think we'd like clinical differentiation to continue to carry the day here. There's no way that we could respond and meet Pfizer's rebates if they are going to be aggressive in that channel, nor do I think we need to. We've had productive discussions with our partners all the way through the channel. They understand what we're trying to accomplish in terms of clinical differentiation and the added reduction in hospitalizations. And here's where the real-world evidence really comes in handy: a 34% reduction in hospitalizations in an independent study relative to tafamidis is super meaningful. These are patients that are quite sick and quite expensive. Long term, these brands will be at parity generally in terms of access; I think clinical differentiation will be where we win. So we do not intend to chase anyone down the rabbit hole of trying to play near-term price dynamics.
Our next question comes from Salim Syed at Mizuho.
Great. Congrats on the quarter, guys, and thanks for the question. Just one from us on this heart-failure publication data on the kidney protection. Obviously, you know Attruby is better than tafamidis in the real-world curves. Just wondering how this adds into sort of that thinking. When you guys are talking to physicians, how important is this kidney protection? How meaningful is it in terms of how they're prescribing a stabilizer and choosing a stabilizer? If we drag that forward a little bit with the list price already being below TAF, what does this eventually mean for Attruby as the market evolves and when tafamidis goes generic?
Salim, thanks for the question. I'm going to let Matt handle how the data is being received by KOLs and then I will add a comment on the generic dynamics.
I think the first thing to note is this is new. Up to this point, it's been about the three-, four-, two-, fifty and early separation, not only how fast Attruby works but how well it works — how many people it keeps out of the hospital and how soon you see the curves separate. That's what's led us through Q2. I think in terms of the kidney data, it's very important to physicians and you're going to see that impact moving forward, which I think is one of the most exciting things about the call today because the kidney data hasn't been out. It's brand new, so you're going to see that impact now as we move forward over the next couple of quarters.
And just to add on this, we do expect the brand to keep growing even after Vyndamax goes generic in mid-2031 in the U.S. There are five reasons for this. First, Attruby is exponentially differentiated as you've heard today — that is driving strength in the treatment-naive segment. Second, stakeholder economics in this market — the specialty pharmacies — do not largely support a preference for generics. You can also see that Pfizer has been successful in finding other franchises, and there is potential upside because if Pfizer reduces promotion post-ROE, that would increase relative share of voice for Attruby. Looking at all of this and analogs, we expect to continue growing even as the market evolves.
We'll move to our next question from Andrew Tsai at Jefferies.
Congrats on the solid execution. So I think this was a quarter where all three of your pipeline programs moved from the clinic into regulatory phases. You got LGMD submitted within five months of the top line, two priority reviews, and no advisory committees planned. It seems like your relationship with the FDA is quite healthy. Could you talk to us in detail about what your regulatory engagement has been like and how you're feeling about the review timelines from here? I'd also be curious about your ex-U.S. interactions too. Thank you.
Sure. I'm happy to take that. I mean, first and foremost, in the rare-disease setting, the gold standard is the ability to run an RCT — a solid RCT with a placebo arm — and we've been able to do that across all three indications here and demonstrate profound functional benefits. One of the senior administrators at the agency once said that we're kind of the poster child of what one tries to do in the rare-disease setting. It's not always the case, of course, but certainly for these three data sets with the p values where they are and the safety profile, the risk-benefit is pretty straightforward as well. Based on all of that, we've had productive discussions with the agency to date and we look forward to continuing to engage. Similarly, in Europe, there has not been a dichotomy in the tenor of our conversations there yet.
Our next question comes from Anupam Rama at JPMorgan.
Hey, guys. Thanks so much for taking the question. I'm thinking a little bit about the November 27, 2026, PDUFA for BBP-418 in limb girdle muscular dystrophy. Sounds like you guys have made a lot of progress here on the field team being hired, trained, and deployed. Can you walk us through what the near-term focus will be to be ready on your launch readiness? And then how you're going about identifying more patients heading into PDUFA to go beyond that 500 patients you talked about being identified today? Thanks so much.
Thanks, Anupam. We will pass to Christine to talk about the BBP-418 launch.
Hi, Anupam. Just as a reminder, this is an opportunity where we think it's a $1 billion peak sales opportunity. We think there are about 7,000 patients in the U.S. and EU with 2,000 to 3,000 in the U.S. In terms of launch readiness in the U.S., we benefit from having a concentrated prescriber base with the majority of patients treated at about 150 MDA centers. As we mentioned, we do have a dedicated sales force that's been fully hired and trained in the field now, really focused on disease awareness and site profiling before the launch. Our MSLs are also fully trained; they've been in the field for over a month. They're focused on disease awareness and increasing awareness of genetic testing, which has been key for driving increasing patient identification and genetic testing. On the patient side, we have identified over 500 patients who are genetically confirmed. That's grown over the course of the year, and we expect it to continue growing. We have seen that genetic testing rates have increased over the past nine months, which is key to increasing the number of patients that are identified, including the fact that we now have a dedicated sales force and MSLs in the field driving awareness. There's also a new dedicated ICD-10 code specific for LGMD2I/R9 that will help with tracking patients and greater visibility as we commercialize BBP-418. On the payer side of things, this is an area of strength for this launch where we can maximize access and price. Market research with payers has been consistently positive. They've been quite receptive to the strength of our data and the unmet need on the patient side. They view the closest price analog as the exon-skipping DMD drug as a comparable patient population for them, and they acknowledge that we have much stronger data because we actually have functional data, not just biomarkers. That's an area of strength for us to launch.
We'll go next to John Boyle at William Blair.
Congrats on the strong quarter, and thanks for taking our question. I wanted to ask on encaleret. Now that you have priority review, the MAA is submitted and diagnoses are increasing each month with the ICD-10 code, wondering if you could walk us through the launch setup into the May 2027 PDUFA date. And as a follow-up with RECLAIM-HP now screening, could you walk us through how you view the size of that opportunity and how you're viewing it as the next leg of growth for the franchise? Thanks.
Thanks, John. I will pass to Ananth to talk about encaleret.
Sure. John, thanks for the great question. On the setup in advance of our PDUFA date for encaleret in ADH1: as we shared today, we see over 2,200 patients uniquely coded under the dedicated ICD-10 code E20.810 for autosomal dominant hypocalcemia. What we see is about 70 patients per month being diagnosed and coded according to that code in claims databases, which is suggestive of the anticipated impact where availability of promising clinical data drives awareness and suspicion to test for ADH1 in the clinic. Between now and PDUFA, we are investing further in raising disease-state awareness; our medical team is meeting with institutions and providers to amplify disease-state awareness efforts and grow familiarity with our evidence. Between now and PDUFA, we will continue to engage with our payer audience; feedback to date has been quite positive. The anticipation for a new, first-in-modality directly targeted to treat ADH1 has been well received among payers and we anticipate constructive dialogue as we approach decisions more closely. To your second question regarding RECLAIM: it's an exciting update that screening activities have started for that Phase 3 study. We anticipate delivering topline results from that study in about 18 months or so. It could be a great opportunity for us to grow the clinical utility of encaleret into the broader chronic hypoparathyroid population. We see around 200,000 individuals in the U.S. and Europe afflicted with chronic hypoparathyroidism; if we're successful in this indication, we see another blockbuster opportunity to grow into.
We'll move to our next question from Derek Archila at Wells Fargo.
Hey, good afternoon. Thanks for taking the question. So in the past, you mentioned a 30% to 40% peak share for Attruby assuming a four-player market with combo use expanding. How does the failure of CARDIO-TTRansform raise that ceiling? And do you plan to update that assumption anytime soon?
Thank you for the question. We're conducting research, and I think we'll probably share more after the CARDIO-TTRansform results are presented more fully at ESC. At that point, we can more formally talk about expectations. As Neil mentioned in his prepared remarks, we do think that the case for combination therapy is scientifically much weaker now, and so that does benefit stabilizers as the main frontline treatment. We expect those things to be positive, but we don't have new market research to share at this point. It would be premature to update assumptions before the medical conference has happened and physicians have a chance to review the full data.
Our next question comes from Luca Issi at RBC.
Great. Congrats on the progress. Maybe on achondroplasia: BioMarin last week mentioned that 100 patients have switched from Voxzogo to YUVIWEL, or less than 10% of all the Voxzogo patients. They're arguing that such a low number suggests the market is sticky and patients are loyal to Voxzogo. What's your view on that number as we think about the launch of infigratinib potentially next year? Thanks so much.
Thanks, Luca. I will pass to Justin to talk about the infigratinib program.
Thanks so much for the question. I think we've been really pleased by what we've heard recently from both BioMarin and Ascendis. There are a lot of favorable tailwinds for our upcoming launch. On the side of things, they continue to increase the treatment rate and build the market globally, really enlarging the pie for everyone across markets. Because it's easier to get a switch than to get a patient who's never been on treatment before, that's been great to see. Based on recent Ascendis numbers, it really validates two of our key assumptions for launch. The first is that there's not that much brand stickiness in this space. Families want their kids to switch; the notion of being an option matters. When we're on the market, not only will we be an option, but we will be, in our view, the most efficacious. Secondly, Ascendis's launch validates that having a more convenient option will help expand the market. We've noticed a huge uptick in outreach since Ascendis's approval, and having the first oral tends to expand the market by two or three times based on multiple analogs from prior launches. So we think the recent data and activity are favorable for our launch.
Next, we'll go to Jason Zemansky at Bank of America.
Good afternoon. Congrats on the nice quarter, and thanks for squeezing us in. BEYONTTRA royalties just reached $15 million for the quarter and look like they're starting to scale quickly. As encaleret, BBP-418, and now infigratinib move toward European decisions, how are you weighing potential partnership structures like the BEYONTTRA agreement versus commercializing independently ex-U.S.? Is there anything you can extrapolate from your experiences about maximizing value abroad? Thanks.
Hi, Jason. Thanks for the question. Our framework for any partnership decision remains that we want to do what is best for patients and shareholders alike and put the asset in the hands of the best owner. For these next three launches, we feel very confident about being able to commercialize them globally on our own. We learned a lot from the Attruby launch and we're excited to grow our international footprint because serving those countries and KOLs helps improve our development engine too. We are well capitalized with approximately $1.7 billion of cash on our balance sheet to fund those launches, and we believe our commercial footprint can be relatively light. That's how we are thinking about it today, but we're always open to suggestions and will evaluate any opportunity through the lens of what's best for shareholders and patients.
Also, it's important to control price globally in an MFN world, so that's what we intend to do.
And next, we'll move to Danielle Brill at Truist Securities.
Hi, guys. Good afternoon. Thanks for taking the question, and congrats on the really strong execution this quarter. It looks like operating loss improved roughly 20% year over year despite the added investment required to support potentially three new launches over the next 12 months. As Attruby continues to scale and the portfolio transitions to a multi-product commercial business, how should investors think about incremental margins and operating leverage from here? What are the key milestones that ultimately drive Bridge to profitability and sustainable cash-flow generation? Thank you.
Hey, Danielle. Thanks for the question. With another quarter behind us, we are increasingly confident in the evolution of the P&L towards a point where we'll start to see breakeven profitability and ultimately cash generation in the relatively near term. To give you a sense for how we think about this: year on year, we're seeing an improvement on the operating line which has been pretty consistent for the last few quarters. Quarter on quarter, though, we're pretty much stable. We expect to be stable on the operating lines for several quarters before that starts to improve again toward the end of the year into next year. To break it down further, you've got two pieces driving this. One is Attruby, which is in margin-expansion mode where OpEx is relatively stable but sales growth continues to improve the margin. That's largely offsetting the investment we're making into upcoming launches. We're currently scaling up activities around field medical marketing and expensing pre-commercial inventory. As we get toward steady state on those activities toward the end of next year, we'll start to see a trend toward improving the operating line, with ultimate breakeven on the horizon as we look into 2027.
And that concludes our Q&A session. I will now turn the call back over to Chinmay for closing remarks.
Thank you, everyone, for joining us for our second quarter earnings call today. We appreciate your interest and we look forward to seeing many of you at our commercial day in New York on October 8, where we will go deeper on commercial readiness and launch strategy across our three upcoming launches. Thank you.
And this concludes today's conference call. Thank you for your participation. You may now disconnect.