BridgeBio Pharma (BBIO) Q2 2026 earnings call transcript

Good afternoon, everyone, and thank you for joining Bridge Bio 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 Outen, our Chief Commercial Officer, who will provide additional detail on our 2B and our launch readiness, and Tom Trimarki, our President and CFO, who will review our financial results. During today's call, we will cover another quarter of consistent growth for a truebie, along with new data reinforcing its clinical differentiation, including the first evidence of direct kidney protection in ATTRCM.

We will then turn to the pipeline, where this quarter, all three of our late stage programs move from data into being with the FDA, with our first producer date now set for November 27. And we will review our financial position, including the billion dollar preferred equity financing completed on July 1, 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 Anant Shreder, Christine Shoe, and Justin Do, who lead our programs with Incalorette, BBB418, and Instagram respectively.

With that, I'll 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 Bridge BIO, 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 Bridge BIO'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 Transform, 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 a true V. I believe we will start to see significant commercial fruit from this in the six to nine month range and beyond judging from analogues. 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 NDA's for LG MD2I, ADH1, and Acondiplasia have been submitted with LG MD2I and ADH1 garnering priority review and are hoping that Acondiplasia might too. Our commercial readiness work is on track, even ahead of what we were able to do with ADTR cardiomyopathy, given our relatively lean resourcing at the time to deliver strong launches.

Third, our chronic hypoperathyroid phase three, 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 the space.

Finally, we anticipate novel trials in areas like Turner and Hypocondiplasia for Infogradinib, a new trial in a two-beat disclosed high-pooten earth, orphan kidney disease for acoramities, 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 a substrate for well over $10 billion in risk-adjusted revenue, with 8 billion of that being post-phase three to day. In addition, our interest in earlier, but still advanced genetic medicine R&D within our gondola pipeline, continued 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 the TRUBI. First and most importantly, we observe continued commercial momentum this quarter, with the TRUBI being the fastest growing brand in the space at 23%. And this growth does not account for the impacts of cardiac transform, our kidney data, and most of the real-world evidence data to date since that 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 transforms important results.

Indeed, we observed a slight down tick 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 growth in it 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.

A true, the strongest tailwind, however, is it's 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 Suracart Failure on Acramanis 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 a truebie 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 a truebie in terms of clinical outcomes, helping to explain this early impact. Furthermore, and intriguingly, the magnitude of the acute dip in EGFR on a truebie is actually important and suggestive of downstream benefit.

More specifically, comparing Acramanis versus placebo subgroups with acute EGFR dips greater than or equal to the median of 4.89 millimeter per 1.73 meter squared, favored Acramanis for all cosmortality or cardiovascular related hospitalization with a whopping hazard ratio of 0.42 with an associated p-value of 0.006.

And 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 in other kidney protective cardiac treatments like SELT2 inhibitors.

In a recently held meeting of nephrologists and cardiologists, one KOL explained to me, it looks like you have a kidney drug here. Building on that, as referred to above, we intend to further interrogate this 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 to pace. 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-wild performance. The most storied of these analogs is likely the eliquist or alto marketplace. Calling back to last quarter, there was an independent propensity-score matched analysis presented at SCAI and since published, which continues to resonate with physicians.

That analysis associated a true beat with a 37% reduction in composite cardiovascular events and a 34% reduction in hospitalizations at six months relative to defamities, with an effect deepening at nine months. Remarkably, there was no observed clinical outcome that did not favor a true B versus Vindamax in all measures except for dizziness and syncopey with statistical significance of less than 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 today pre-print analysis that parenthetically has been downloaded more than 400 times now, showing again a true B out performance as compared to Vindamax. Importantly, in this study, a 34% reduction in diuretic intensification, heart failure, hospitalization, and mortality was observed, again statistically significantly, 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 the true beat continues to perform well there, and that then these several RWE studies will form the basis for decision-making and guideline updates.

The growing body of research supporting a true beat 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 cardiac transforms studying a Plongerson in ATTR cardiomyopathy readout, and the study did not meet its 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 to today null from a trial data perspective. Given the similar degrees of knockdown between a Plongerson and Fertissa-Ran, 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 observe from a true beat at 30 months? And two, does monotherapy knockdown actually not outperform a partial stabilizer into famidus as we actually observed in Helios B? Recall, of course, that in addition to the real-world evidence I just cited, everywhere we looked in our Tribute Trial, Acoramidus outperformed to famidus.

The conclusions of this important study run by AstraZeneca and ION is we believe will likely reinforce the case for stabilizers first. And if the monotherapy benefit, again, lags in time, this is observed with Bertissa-Ran, and in magnitude of effect as compared with the true beat, we believe this begins to make an even stronger case for using a true beat first.

First, in the second line setting. Now, I'd like to discuss the three pipeline programs that are moved into regulatory review this quarter, and which we are preparing to launch. For BVP-418, our LG MD2I program, the FDA accepted our NDA on May 27th with priority review. The PDUFA date is November 27th, 2026, and there is no advisory committee plan. We continue to have positive interactions with the agency.

This is in mind to be the next approval on our portfolio, and it would be the first approved therapy for LG MD2I, a devastating condition affecting a little more than 1,000 patients in the U. S. alone with significant unmet need. There's really no displace incredible 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 LG MD space, and perhaps the broader muscular dystrophy space, given the 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 the 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 nonambulatory 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 LG MD or background 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 a calculate for EH1, the FDA accepted our NDA on July 22nd, with a PDUFA target action date of May 8th, 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 27th, and it is under review. In Colorado, it would be the first therapy approved for EH1 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, and it's been driven by genetic testing, awareness education, use of the ICD 10 code, and bridge bios supported family testing events.

We have also completed an enrollment in the first of four cohorts in our pediatric ADH1 study and are preparing to open cohort 2. But ADH1 approval is the beginning of the calories potential, not the end. Chronic upper parathyroidism affects some 200,000 patients in the US and EU, a blockbuster opportunity in and of itself, whereas discussed last quarter, we see a real appetite for an oral option that corrects both hypocalcemia and hypercalciria. I want to spend a minute on this opportunity because I think it's been overlooked significantly 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 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 CHP patients actually being hypercalciria. 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, that many individuals would prefer an oral medicine.

I think some may have discounted this opportunity based on likely probability technical success. That I believe is a mistake. First, the path of mechanism here is well-described. Recall first that the hypercalciria in chronic HP arises from three independent contributors. One, loss of calcium reabsorption at the distal methron, 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 in calories action on the calcium sensing receptor has been shown to increase pericellular reabsorption of calcium in the thick ascending limb. By reducing clodin 14 expression, which in turn decreases the amount that integrates into the clodin 1619 complex, which acts as a calcium urea promoting poor blocking component. This mechanistic rationale helps to explain the observation from our proof of concept phase two, where 80% of post-surgical parathyroid patients administered within calories achieve 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-time setting that exists for these drugs, namely the extensive data from the legacy clinical development program of and calorie in osteoporosis participants, expressing wild-type calcium sensing receptor, like the chronic upper parathyroidism population that we intend to study in the reclaimed HP trial.

And recall that in that osteoporosis study, the drug demonstrated dose proportional increases in serum calcium at daily doses of 15 milligrams 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 sites for the reclaimed trial, our global phase three, and a begun screening with FBI imminent, and a trial read out expected in the next 18 months.

Okay, finally, I'll come to Infograd NIB, our oral treatment for A-Contraplasia, where we presented our phase three propel three results at the International Conference on Children's Bone Health on June 30th, and simultaneously published them in the New World Journal of Medicine. The only A-Contraplasia program with phase three results in the New World Journal. Following that publication, I'm excited to announce we've submitted our NDA, and we are targeting an M&A submission in Q4 this year. We hope to see NDA acceptance and ideally, priority review in Q4 of 2026 with approval following in mid-2027.

Approval would make Infograd NIB the first FGFR three targeted oral therapeutic for A-Contraplasia. And on top of its oral dosing advantage, it remains the only therapy with efficacy measures beyond annualized high velocity demonstrated in a placebo controlled setting at 52 weeks, including proportionality. Adding to this, we demonstrated a clear and functional differentiator in our phase three results with a statistically significant 0.37 standard deviation improvement on arm span with a p-value of less than 0.001.

This is the first ever placebo controlled arm span benefit in an A-Contraplasia trial. We look forward to presenting more data in the second half of this year and continuing to build Infograd NIB'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 team 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 A-Contraplasia 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 Gondola Bio, where bridge bio 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 EOP2 meeting with the agency, we will be initiating a Phase 2B3 study in Q3 of this year.

Critically, given the 80-plus percent magnitude of PP9 reduction coupled with the quick onset of action and safe profile, the agency suggested that the 2B could form the basis of registration if PP9 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-1A E-Tripsin, Neurofibrotosis Type 1, and CMT-1A. 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 2027-28 timeframe.

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'll pass it over to Matt.

Thanks, Neal. Q2 was another strong quarter to demonstrate a consistent growth in the treatment naive segment for a truebie as physicians are increasingly starting and keeping patients on a truebie. That 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 for 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 fourth vindicill 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. 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 walks 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, the physicians and with payers, the sponsor generated data does not. We expect additional independent real world work to read out over the balance of the year. On cardio transform, 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 a true V 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 Acoramities to reach blockbuster 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 Acoramities, which includes Beyond Trust sales recorded by our partners outside of the United States. It is not a forecast for the U. S. at Ruby net product revenue.

For the balance of my time, I want to focus on the three approvals ahead of us. The atroovy 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 bridge bios history.

Let me take them an expected order of approval. First, BBP418. LGMD2IR9 has never had an approved therapy. Approval would mark the first for LGMD2IR9 and the first for any form of Lindgirdle 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 teams 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, incalorate in ADH1. At the end of July, the FDA granted priority review for incalorate. The PDUFA target action date is May 8th, 2006, and no advisory committee meeting is 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 sensor receptor, which causes low serum calcium, low or inappropriately normal PTH, and it won't pronounce increase in urine calcium. Then hypo-parathyroidism generally.

Incalorate 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 BVP418, we are engaged early with payers, so that the clinical rationale is well understood before a decision.

Third, infogratinid in a contraplasia. We have submitted the NDA and we anticipate approval in mid-2027. Unlike the other two launches, infogratinid enters a 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 infogratinid is high. The ability to give this medicine as a small, once daily capsule is about 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. Infogratinid 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 shops. 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 pre-specified three to eight-year-old subgroup. Operationally, our commercial infrastructure continues to build, and 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 Accondroplasia community over the past seven years is underpinning how we are approaching this launch.

In short, we are on track across all three programs. With that, I'll turn the call over to Tom.

Thank you, Matt. Good afternoon, everyone. I'll now walk to our financial results for the second quarter of 2026. Our commentary will focus on gap financials, once otherwise noted. Global revenues for the second quarter of 2026 were $243.7 million compared to $110.6 million in the same period in 2025. The $133.1 million increase was primarily driven by a $159 million increase in a truly net product revenue.

A truly net product revenue in the quarter was $222.4 million compared to $71.5 million in the same period last year. Royalty revenue increased to $15.4 million compared to $1.6 million in the same period last year, primarily earned from net product sales of Deontra in the EU in 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 election agreement following pricing approval in Japan. Total operating expenses for the second quarter of 2026 were $335.7 million compared to $241.2 million in the same period last year.

A $94.5 million increase was like deliberate and disciplined investment in the true and 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, and it proved that $27.2 million were approximately 20% year over year.

Now onto the balance sheet. As of June 30, 2026, our cash equivalents and marginal securities were $720.2 million. Subsequent to the quarter end, on July 1, 2026, we closed the $1 billion preferred equity investment led by 6th Street, with participation from healthcare royalty, putting our cash balance at approximately $1.7 billion as of July 1, 2026. We believe our current cash position provides us with a significant runway to fund our operating activities, execute on three potential launches for the next 12 months, and continue to invest in a true, these commercial growth, all while maintaining the financial discipline we've demonstrated the date.

With that, I'll turn the call back over to Chimway. Thank you, Neil, Matt, and Tom.

I'm sorry, I'm going to pass down to my comment on the commercial dynamics and then I'll pass on to me if he wants to add things on cardio transform expectations that you see. Okay, thanks for the question, Tyler. I think there's two interesting components here. There's the reason that a true be has done so well today, namely how quickly a true be 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 today 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 transform.

And this is going to add on to the earlier messaging and continue to push share forward in the future.

And I'll let you add on with the cardio transform helps. Yeah, I guess I just say, I mean, 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 transform data set. So just be a larger pool. And in that pool, I think, you know, the mass point will continue to differentiate. And I think we're going to see the fruit that I mentioned in my comments on the real world evidence, keeping differentiation.

Up here, really, by kind of like half a year from now or so, if you look at analogs, it generally takes about 69 months to pull through some of this data, obviously also dependent on what each essay was like in terms of the independent RWE analysis. But it kind of continues to go the way of a true be.

I mean, you know, as you well know, it's sort of like, as you start to, as you start to connect all the docs from. By chemistry to serum TTR, I mean, big per deciliter is a 5% decrease in mortality risk in 30 months.

To, you know, all of the real world evidence against both survival, at least we'll see that HSA. We saw some hints of that with the mozzery and independent more data around the time that we launched and hospitalization 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 get to continue to hit. I mean, my expectation would be that we really hit a positive second derivative here and continue to grow pretty aggressively in the front line.

Over the coming 12, 18 months. So let's see.

Thank you. Yeah, that's a question that maybe I'll start and you can add on, you know, I say it's a little early for us to get feedback from payers on the KOL side for sure. I mean, we've been hearing, I think a bit of surprise, honestly, and. You know, there are there are folks that can be convinced with biochemistry and biophysics, but I think a large trial like this convinced a lot of folks and might be changing folks mind. So I do think stabilizer will be an increasing, increasingly large part. They already are a large part, but an increasing large part of the front line. And I think that's where the reaction will be in this category.

I'd say, you know, the three things that we're looking for with regard to cardio transform. I do think a Plonderson and food have a very similar knockdown profile. We have to look at the particle kinetics and see whether a Plonderson is slightly superior to to boot to food. Obviously, it's a long time to get to its mean max knockdown, but that'll be the first thing that we'll be intriguing to look at. And then within the context of the clinical data.

You know, first and foremost, what's the 30 month data look like, is anyone getting to 3 42 50. And to mass point, 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 you know, that basically a truly will look superior 30 months, but if there's no early separation, it really starts to suggest that you ought to be using a true beat. In that switch setting, just given both magnitude of benefit and the early onset now well described by this kidney data that we put out and we'll continue to elaborate on.

I think the second super intriguing point will be to see whether or not monotherapy knockdown actually outperforms a partial stabilizer. You know, people sometimes I know you and I have chatted about this, but you know, people sometimes forget that in Gileos D. And that would tell us that all Jack Baker that we didn't significantly outperform tap, which was a bit of a head scratcher to me based on the toxic monomer hypothesis. Until you look at the pharmacokinetics and a year again, if if a knockdown doesn't outperform a partial stabilizer, recall we've got a stabilizer that outperformed tap and every single part of the attribute trial that we looked at in all major rw studies. And so again, starts to establish, I think, a true V as a superior efficacious agent as compared to both not towns and and the partial stabilizer of Pfizer.

So I'll do the second big thing we're looking for. Yeah.

No, I mean, that's, that's 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 is the backbone of therapy. And again, you're coming to think on the partial stabilizer versus a near complete stabilizer. That's kind of kind of where we are. And I don't think anything with the ESC is going to change that based on the initial results.

Yeah. That's an important question. I mean, I think we'd like clinical differentiation to continue to carry the day here week. There's no way that we could respond and meet positive rebates. If they're going to be aggressive in a channel, no, I think we need to. I think we've had productive discussions with our partners all the way through basically the channel. Understand what we're trying to accomplish in terms of clinical differentiation in terms of the added reduction in hospitalization.

Here's where the real world evidence really comes at handy. I mean, a 35% or 34% in an independent study reduction in hospitalization as compared to TAF. That's super meaningful. These are patients that are quite, quite expensive. And there's some untoward things that can also happen when you favor one brand over the other. So I think long term, these brands will be in parity generally in terms of access. And then I think clinical differentiation will be where we went. So we do not intend to take one down the rabbit hole of trying to play near term price dynamic games.

I'm going to let Matt handle all the kidney data being received by KLLs. Yeah, I mean, I think first thing to know, this is new. So up to this point, it's been about the 34250. As Neil mentioned, it's about early separation and that's not only how fast a true B works, but how well it works, how many people it keeps out of the hospital, how soon you see the curves separate. So 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 that, to me, is probably 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.

Yeah, and just to bet on that. And then there are five reasons for it, right? I think the first is a true B is gonna create a differentiator. You put a lot about that on the call today. That is driving the strength and treatment. I mean, for us and I think it's going to keep driving the strength there. The second, which I think is less understood by folks is that they call it economics in this market, especially BSPs. They don't largely support a preference for genetics.

I think you can also see that by just being successful and defining other franchises. And I think that there's a potential for some outside because if five of the top promoting posture, we backward increase relative share of voice for a true B. I think if you look at all of this and you look at all the analysis on analogs, which I know you and Bennett have some time on it.

I think that we expect that even as opposed to markets, let's put in stabilizers, both generic and they're completely stabilized in order to keep growing.

So can I just build on one point that that that that make that the kidney data is super fresh. So, you know, we're going to have to see in the next six to that month kind of how it changes. First part of the behavior, but first and foremost, I think it's important because the actual mechanism of turning down toxic monomer, you wouldn't expect to pick up impact as early as 28 days or one month. So here now you have a viable mechanism by which you have this early onset of efficacy. And, you know, as I mentioned in my in my remarks, I hinted at like it was previously sort of considered a harmful piece of our label.

But I think now what you see is the greater that give you nation early, the better off you are later in terms of both part of as for hospitalization and death. So that's also a profound suggestion here that I think will be very important on a go forward basis. And you have to remember like 50% of the patients close to 50% of patients. So they have some sort of kidney involvement. So this is an important, this protective signature is going to be an important piece. We believe the emerging story here, you know, and potentially an interesting piece of the story as I think we can move to be into novel indications.

Sure. I'm happy to take that. I mean, I think first and foremost, as you probably know in the rare disease setting, kind of the gold standard is the ability to run in RCT, a solid RCT with a placebo arm. And we've been able to do that across all three indications here and demonstrate the found functional benefit. So, you know, I think one of the one of the senior administrators at the agency once said that that will kind of the poster child of what one tries to do, at least in the rare disease setting. It's not obviously always going to be the case, for instance, in the can of entities, we may not be able to run in analogous travel.

Certainly for these three data sets with the D values where they are with the safety where it is. I mean, you know, people forget that would be small molecules. We've been able to provide an exquisite safety profile. So the risk benefit is pretty straightforward as well. So yeah, based on all of that, we've had productive discussions with the agency today. You know, we look forward to getting to engage them on that front. And similarly, I'd say in Europe as well. There hasn't been a dichotomy between the tenor of our conversations area.

We're going to bust on to Christine to talk about doesn't go to launch. Hi, Adam. This is a reminder. This is an opportunity where we think it's a $1 billion peak sales opportunity. We think there's 7,000 patients in the US and EU with two to 3,000 in the US. In the US, in terms of launch readiness, we do benefit from having a concentrated prescriber base with the majority of patients treated about 150 NBA centers.

So, as we mentioned, we do have a dedicated sales force that's been fully hired and trained in this field now. Really focused on using 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 also focused on using awareness and increasing the awareness of genetic testing. And that's been key for driving increasing patient ID and genetic testing. On the patient side of things, we have identified the over 1500 patients who are genetically confirmed. That's actually grown over the course of the year and we would expect it to actually continue growing. We have seen that genetic testing rates have also increased over the past nine months. And that is a set of key to increasing the number of patients that are identified, including the fact that we now have dedicated sales force as well as MSLs in the field of driving awareness.

There's also a new dedicated ICD-10 code specific for LGM-D2I slash R9. And that's also going to help with tracking patients in just greater visibility as we commercialize CT4.8.

On the payer side of things, this is an area of strength for this launch where we can really maximize access and price.

The market research with payers has been consistently positive. They've been quite receptive to the strength of our data and the on that need on the patient side. They view the closest price analog as the exome skipping D and D drugs as a comparable patient population for them. And I guess the ones that have it here, they even acknowledge that we have much stronger data because we actually have the functional data. It's not just based on biomarkers. And so that's an area of strength for us to launch.

John, thanks for the great question. Over 2200 patients uniquely coded under the dedicated, ICD-10 code, which is E20.810 for autosomal dominant hypokalctemia. What we see is about 70 patients per month have been diagnosed and coded according to that code in the claims databases and it's suggestive of what we would have anticipated, which is the availability of promising and positive. Clinical data, driving awareness and suspicion to test for each one of the clinic.

And between now and to do as one way expect, we're investing further and. Enraging the state awareness and we have our medical team.

Meeting with institutions and providers amplifying the state awareness efforts in growing familiarity with our evidence. And between now and to do as well, we will continue to engage with our pair audience to date. The interactions have been quite positive. The anticipation for a new and first modality directly targeted to treat ADHD one has been quite well received amongst the pair audience and we anticipate a constructive dialogue as we approach people more closely. And then to your second question regarding reclaim, it's a really exciting update today as we share that. Screen activities have started for that phase 3 study.

We anticipate deliver top line results from that day in about 18 months or so. And it might be a great opportunity for us to grow the clinical utility of the calories into the broader chronic hypo parathyroid population. We see around 200,000 individuals in the US and Europe to be afflicted with chronic hypo parathyroidism. If we're successful at this indication, we see another blockbuster opportunity for us to grow into.

Yeah, thank you for the question. We're conducting market research and I think that will probably keep it all tomorrow. After the cardio transform results come out more fully at the end. And so at that point, we can more formally talk about what we expected. I think as Neil mentioned in his subject remarks, we do think that the case for combo therapy scientifically is quite now. And so I think that that does benefit and I think the stabilizers should also remain frontline as we discussed. So we expect those things to be positive, but we don't have new market research to share at this point. It would be a bit preliminary to the board.

So micro conference and half in positions of a chance to digest all of it. Great question.

I'm going to pass it on to just to talk about the Instagram program. Yeah, thanks so much for the question. Yeah, I think we've been really pleased that what we've heard the last few weeks from both bomber and vendors. I think there's a lot of favorable tailwinds for our upcoming launch. You know, on the Byron side of things, they continue to increase the treatment rate and build the market globally and largely in the eyes for everyone across all markets. You know, because easier to get a switch than to get a patient who's never been on a trip before. I mean, that's really great to see they're launching. All right, there. Now, based on the recent incentives numbers, you're really valuable to our key assumptions for launch.

The first is that there's really not that much brand ticketed to the space. Now, families want their kids to switch the notion of being option. And when we're on the market, not only will we have a local being option, but by far, I'm not that patient. And so send us having a strong launch here. It's different. If families and HPC think about which and think about new options and ever since the sentence of the group will be ignored to huge uptake and outreach in the HPC. Now, the second key assumption that a sentence is launched validate is that having more than being optionable to expand the market. You know, I think the sentence is being a good chunk of their trip.

And I use groups from families who never won on box over. You can't just do something in the math based on Byron and send it to the marks. And we know from multiple analogs from prior launches that they'll deliver the first month or 10 to expand the market by two at three times. So we think in totality.

Some of the numbers we're seeing for vote, Byron, and the sentence in the remarks is going to be retained while we're on launch.

Hey Jason, it's great to hear from you and thank you for the question. Our framework for any partnership decision always remains. We want to do what is going to be best for patients and shareholders alike. And we want to put the asset in the hands of the person that that is the best owner. I think that we think for these next three launches.

We feel very confident about being able to commercialize them globally on our own. I think we've learned a lot from the truly launch. And I think we're excited to grow our footprint internationally. I think actually serving those countries and KLLs. It's going to help us and do what our development attention to. So that's how we're thinking about it. Obviously with the fact that we have about 1.7 billion of cash in our balance sheets, we're very well capitalized to fund those launches. And I think that the footprint is also going to be light as we discussed before.

So I think that's how we're thinking about it today. But, you know, we're always open to interesting suggestions and ideas. And I'll, you know, evaluate as what are our shareholders and patients that we wish to sort of.

Well, also it's important to control price globally. And I'm a fan world. So that's what we intend to do.

Thanks for the question. So I would say with another quarter behind us, we're increasingly confident in the evolution of the P&L towards a point where we'll start to see breakeven probability and also like cash generation in the in the relative near term. Just to give you a sense for how we think of it. So we look year on year, we're seeing an improvement on the operating line, which is a pretty consistent year on year for the last few quarters.

Quarter on quarter, though, we're pretty much stable. We expect to be stable on the operating lines of the next several quarters where that starts to improve again towards the end of the year and the next year. To break that down a bit further, you've got two pieces really driving this one is a true V, which is in basically the margin expansion mode where.

Off X is relatively stable, but we're seeing obviously sales growth continue to improve the margin. That's pretty much offsetting the investment we're making into the upcoming watches. So we're scaling up all the activities around field medical marketing, as well as expensing pre commercial inventory right now. So as we get to sort of steady state on those activities towards the end of next year, we'll start to see again a trend towards improving the operating line also a great even on the horizon as we look into 27.

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.