BridgeBio Pharma, Inc. (BBIO) Q1 2026 Earnings Call

0:00 Hear the whistle blowing. I can hear the mighty roar. I can hear the horses prancing in the postures of the lord. Oh, the train is coming, My baby's

4:45 coming back now on the next train. I can hear the whistle blowing. I can hear the mighty roar. I can hear the horses prancing in the pastures of the lord. Oh, the train is coming, Good afternoon. I will be your conference operator today.

5:35 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. Thank you. Before we begin, I would like to remind everyone that today's call may contain forward looking statements within the meaning of the federal securities laws, including, but not limited to, statements about BridgeBio's future operating and financial performance, business plans and prospects and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward looking statements. For a discussion of these risks and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings.

6:25 All statements made here are based on information available to BridgeBio as of today, 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 first quarter twenty twenty six earnings call. I'm Chunai Shukla, senior vice president, strategic finance. With me are Neil Kumar, our CEO Matt Alton, our chief commercial officer and Tom Trimarkey, our president and chief financial officer. On today's call, Neil will walk through our commercial pipeline and business updates, with Matt providing additional commercial detail and Tom covering financials.

7:11 Following our prepared remarks, we will open the call for questions. For the q and a session, we will be joined by Anand Shreedhar, Anna Wade, and Justin To, who will lead our programs with Encaladec, BBIO four one eight, and entiragatinib, respectively. With that, I'll turn it over to Neil. Thanks, Shimee, and thanks everyone for joining us today. As always, this is a forum in which we communicate salient aspects of our business that are of interest to investors, and we welcome your questions and feedback along the way. I wanna spend the bulk of my time today talking about three things. The first is the Atruvio franchise, and I wanna talk about our continued commercial momentum there and how we think about clinical differentiation. Importantly, these two things, plus the economics associated with the Part D orphan drug channel, underpin our confidence that it truly will continue to grow even past 2032.

8:01 The second thing I wanna discuss is launch readiness against the three exciting first in class or best in class brands we have in AVH1, LGMD two eye, and achondroplasia. Although there are no major near term clinical catalysts for any of these brands, there is a tremendous amount of activity going toward ensuring expeditious and high quality approvals and launches. In its history, BridgeBio has demonstrated across now three approved products with hopefully three more to come, the ability to take on post phase three regulatory submission activities at very high quality, and we intend to build on this tradition with these new brands. I'll end my comments by addressing the current gap between our intrinsic value and where our shares trade today. I've heard from investors in the past that too much NPV talk is not what people turn into these calls to hear. But at this point, it is my responsibility to discuss matters related to capturing the value that investors who have been in our stock for a long time have helped create.

8:55 Our focus at BridgeBio has always been on long term value creation and on reliably being able to take in money to do more work over time. And by the way, our activities across the BridgeBio ecosystem show that there are many more of these r and d opportunities out there. But this model is reliant on capturing the value of the work for investors, which is why today I'll be discussing a share buyback program that will commence immediately. Let me begin my comments by talking about Atruvio. As many of you have read in the press release, we've had a 186 we've had a $180,600,000 of Atruby sales in US Atruby net product revenue this quarter, which represents a 24% growth from the last quarter and a 392% growth year on year, and is consistent with the brand globally becoming a blockbuster in 2026.

9:41 Our focus continues to be on winning in the frontline, while we believe a 95% stabilizer that preserves the native tetramer is not only the optimal solution, but even against combinations, is the only solution one should start with, as it provides the highest degree of management of TTR monomer deposition, provides impact more quickly, and is consistent which is consistent with the pharmacokinetics of TTR stabilization, and ultimately achieves all of this in a cost efficient and easy to access manner. Parenthetically, our data suggests a tripling in combo use with Atruvi with the various knockdowns, suggesting that the message that one should reach for a better stabilizer even in combination is resonating. As it relates to the frontline, our major competition continues to be Pfizer, and our best understanding of our share is that it has grown from the NBRx share I quoted at the JPM talk of 25% even furthermore, but still remains behind what Pfizer has been able to accomplish in the frontline.

10:36 We believe that in this quarter, total new patient starts in the category were in excess of 6,100 new patients, and we believe that for the first time, we are convincingly the second brand by volume in this space. There's more work to be done, but all of these trends continue to be in the right direction for us. So how do we pour some gasoline on these growing sales? The obvious way to do that in our mind is through clinical differentiation. We began to see reasonable inclines in the second derivative of our growth as the serum TTR story began to evolve in the marketplace, with multiple papers suggesting the higher levels of serum TTR associated with lower levels of mortality at thirty months. As a reminder, every mgdL of incremental increase in serum TTR seems to lead to a five percent decrease in mortality risk at thirty months, meaning a more potent stabilizer, and we do not hear from many physicians quibbling with the fact that Entruby is a more potent stabilizer, it is, should lead to better outcomes for the patients that we serve.

11:34 Building on that, we are now beginning to explore and are confident in the outperformance of acarambitus versus tucambitus in the real world setting. There were only really two real world evidence studies reported to date, survival studies done in Columbia and by doctor Madri that showed outperformance of acoramidis both, but those were comparing our trial data and not at that point we didn't have enough time at that point to be in the market long enough to demonstrate anything in the classic real world evidence setting. That is now changing. At FCAI, an independent real world evidence study presented by the Valley Health System of Nevada, reveals statistically significant outcome improvements associated with acoramidis as compared to defamidis. Building on this, we have a study in MedRxiv that we will publish shortly in a major journal showing that Atruvio reduces diuretic intensification by forty three percent as compared to tafamidis.

12:25 We intend to continue studying and publishing on Atruvio's differentiation in the real world setting and are glad to see the cardiology community doing so independently. Interestingly, one of the benefits of Acoramidis that was identified in the independent real world evidence study was a lower incidence of acute kidney injury. As I mentioned in my JPMorgan talk, we are driving toward what we believe will be a seminal publication with potential impact for patients, physicians, and even on our label as it discusses an observed rapid hemodynamically mediated renal protective effect, which is unique to Atruvio as opposed to the other stabilizers and knockdowns in the space. We continue to present and publish on acroamidis at major medical meetings as well. At ACC recently, we presented long term efficacy and safety data from our Phase III open label extension showing sustained clinical benefit from acromegaly at month fifty four, including a remarkable statistically significant risk reduction of forty five percent in all cause mortality with a P value of less than 0.0001 and a forty nine percent reduction in cardiovascular mortality, again, with a similar p value versus placebo to afaramidis.

13:34 All right. I'd to turn to the rest of the pipeline now. On LGMD2I, as I alluded to in my earlier comments, our team was able to go from top line unit to NDA submission in one hundred and fifty five days, consistent with our ethos that every minute counts and the fast pace that we have previously set with regard to our TTR regulatory submissions. We continue to work closely with the agency and foreign regulators to bring this medicine as expeditiously as possible to the patients who need it. I had the opportunity to attend a top line result presentation recently in Orlando at the NDA meeting. It was a trip I won't soon forget. I was struck by the excitement of our data that our data generated, not only within the LGMD2I community, but more broadly, given the striking results associated with BPP four eighteen, suggest that functional improvement is possible when targeting well described conditions at their source.

14:24 Given the already 500 or so genetically confirmed patients in The United States to date, the highly engaged patient community, and physician education being conducted by the team, all of this augurs well for a positive launch dynamic. Moving to ADH one, I'll be leaving from here to a very similar gathering, a top line presentation of our CALIBRATE phase three data at the European Congress of Endocrinology in just a matter of days. Here again, we'll be looking to drive excitement into the broader physician community and to educate the patient community and establish a base of data that together with our publication of our Phase III data can ensure market building exercises can continue with high fidelity. Importantly, BridgeBio has been supporting via grant family genetic testing events in The United States that continue to identify new patients with relatively high yield.

15:12 Although we have been we're launching at a time when a vast majority of patients with eighty eight one have not been identified yet, the combo of genetic testing, ICD-ten codes, and broad disease awareness education, our belief that we will be able to find ever more patients in need of this compelling drug product. Furthermore, our Phase III in chronic hyperparathyroidism will be commencing this summer and is bolstered by recent published work that illuminates the central role that the calcium sensing receptor in the kidney plays in regulating calcium metabolism. Finally, moving to achondroplasia, the results from this trial came after LGMD2I and ADH1, but I suspect given the strength of the results, prominence of the condition and the remarkable KOLs we're privileged to partner with that the Phase III manuscript will be forthcoming in a major medical publication, and we anticipate presenting the full PROPEL three data set at a medical conference in the second half of twenty twenty six.

16:08 Early commercial research here suggests unaided awareness in excess of forty percent amidst the prescribing physician community, which for those of you who have commercialized spreads know is a very high starting point and certainly higher than we've seen before in our own portfolio. Finally, I wanna touch on the share repurchase program that we announced today. To do so, I'd like to go back to BridgeBio's founding principles. The company was built on two things, to help as many patients as possible and to establish a corporate and financial model that creates and captures value in predictable, responsible ways. That value capture has always been part of the mission, while we talk about NPV, while we anchor to intrinsic value, while we try to make the right economic decision at every fork. The reason for that is because of the capture value, more capital flows into drug development over time, and more patients get served by us and others employing our decentralized diversified model.

17:00 Unfortunately, at this moment, we have not adequately captured value from the investors we serve given the large disconnect between our NPV per share and our firm's intrinsic value. Even with the revision of Indamax's entry from 2035 to mid-two thousand and thirty one or early two thousand thirty two, our intrinsic value remains markedly higher where we've been able to get the shares to trade to today for investors. To that end, the Board has authorized a $500,000,000 share repurchase program. These repurchases should allow our shareholders to concentrate their ownership in a portfolio whose risk profile has fundamentally improved. Of note, we have employed this technique in the past some six times some six times. In aggregate, even accounting for the pre part a buyback, we have driven substantial returns for investors with our share repurchases. While we have this lever, we still believe in putting capital into our launches and advancing our clinical trials.

17:51 Repurchases are additive and opportunistic, not substitutive, and are a direct result of our strong balance sheet. On the balance sheet point, we will always size deployment such that we preserve full flexibility to finance every creditable program and activity in our portfolio. Plenty of liquidity and the ability to easily service our liabilities is a requirement before we deploy dollars into the buyback. Okay. With that, I'll turn the call over to Matt to talk more about our commercial efforts. Thank you, Neil, and good afternoon, everyone. Q one was another strong quarter for Atruvi, delivering an impressive 24% increase in net sales from Q4 and a 392% year over year increase from Q1 twenty twenty five. Growth was driven by our existing and expanded sales teams accelerating new patient starts and first line share gains.

18:42 There are several factors which contributed to these results. Market momentum has remained strong. New to brand market share hit its fastest quarter over quarter growth since Q1 twenty twenty five, and first line patients have increased each and every month of the launch. Bill rates, cap rates, gross to net, compliance, and persistency all continue to remain in line with expectations. Insurance author reauthorization dynamics has been a topic of industry discussion this quarter, and I want to address them directly. Atruvi did not experience reauthorization disruptions for two reasons. Part D as in David is a continuous plan based model, which avoids the annual renewal friction of Part B as in boy. That structural advantage matters.

19:28 In addition, in 2025, the average co pay for attributed patients was only $190 for the entire year, making many patients pay only $0 out of pocket as well. Our field teams executed with exceptional discipline to keep patients on therapy without interruption. We hire exceptional people, and those people make sure that any patient who wants a near complete stabilizer can get a Truvy and importantly can stay on Truvy. Turning to our pipeline, we are encouraged by early indicators across our three anticipated near term launches in LGMD2 IR9, ADH1 and achondroplasia. In LGMD2 IR9, we are entering a disease area where no approved therapy exists. We've onboard the commercial leadership team and have set up a specialized patient identification and field reimbursement infrastructure.

20:18 Our goal is simple, find every patient who can benefit and be ready to serve them from day one of approval. In ADH-one, our claims analysis has already identified nearly two thousand patients in The U. S, and that number continues to grow. We've built a dedicated sales leadership team and patient infrastructure tailored to this community. ImpellerAd would be the first medication to target the disease mechanism correctly and it's orally administrated. Physician excitement is high and we're ready to move immediately at approval. In achondroplasia, we are preparing for a global launch with a truly differentiated clinical profile. Infogratenib is the first medication to demonstrate statistically significant improvement in body proportionality, not just improvements in average height velocity and the only oral option in the category.

21:07 For families seeking an alternative to injectables or returning to treatment after a negative experience, the clinical profile and route of administration of impregretinib is very compelling. To summarize, Q1 continues to reflect a durable growth trajectory for TrueBio and proof of the commercial capability we've built at BridgeBio, an organization that knows how to launch, scale and build franchises. We remain focused on execution for patients, for families, for prescribers and for long term value creation. I'll now turn the call over to Tom. Thank you, Matt, and good afternoon, everyone. I'll now walk through our financial results for the first quarter of twenty twenty six. Our commentary will focus on GAAP financials unless otherwise noted. Total revenues for the first quarter of twenty twenty six were $194,500,000 compared to $116,600,000 for the same period of 2025.

22:01 The $77,900,000 increase was primarily driven by a $143,900,000 increase in Intruby net product revenue. Intruby net product revenue in the quarter was $180,600,000 compared to thirty six point seven million dollars for the same period last year. Royalty revenue increased by $9,300,000 to $9,500,000 primarily earned from net product sales of BBIONTRA in Europe and Japan. License and services revenue was $4,400,000 compared to $79,700,000 for the same period last year. The decline reflects the recognition of $1,750,000 regulatory milestone from the prior year. Total operating expenses for the first quarter of twenty twenty six were $290,500,000 compared to $218,400,000 for the same period last year.

22:51 The $72,100,000 increase reflects deliberate and disciplined investment in TrueBio and preparations for our three upcoming launches. SG and A expenses were $163,900,000 an increase of $57,500,000 compared to the same period last year, reflecting measured investment in our commercial activities. R and D expenses were $126,600,000 an increase of $15,200,000 driven by investments in medical affairs and CMC in support of our next few launches. Turning to the operating line. In the first quarter, we recorded a $106,000,000 operating loss. Over the last five quarters, our loss from operations has narrowed by more than 50% due to OpEx discipline and with strong execution on Intrusion.

23:38 Looking at the quarterly trend, if we back out one time milestone payments, we've seen an improvement in the operating line every quarter since Intrusion launched. Looking ahead, we expect the trend in loss from operations to flatten over the next two quarters as we ramp up launch readiness activities for the next three products and continue narrowing toward the end of this year to 0.67 as we transition to a P and L breakeven, followed by cash flow positivity which we expect to be sustainable from that point on. Turning to the balance sheet. We ended the first quarter with $940,200,000 in cash, cash equivalents and marketable securities compared to $587,500,000 at the end of last year. We believe our current cash position provides us with significant runway to fund our operating activities, advance our three late stage programs for the approval of launch and continue to invest in truly growth, all while maintaining financial discipline we have demonstrated to date. With that, I'll turn the call back over to Chairman. Thank you, Neil, Mike, and Tom. Operator, please open the line for questions now.

24:36 Thank you. Ladies and gentlemen, we will now begin the question and answer session. In the interest of time, we kindly ask everyone to limit themselves to one question only. Thank you. Our first question comes from the line of Tyler Van Buren with TD Cowen. Please go ahead. Hello, this is Sam on for Tyler. Thanks very much for taking our questions and congrats on another strong quarter. I was just wondering, you guys talk about what's driving the continued Ichthruvi acceleration and specifically what you're seeing in those treatment naive patients?

25:25 Thank you very much. Hey. This is Matt. I'll I'll take that one, and thanks for the question. We're definitely excited about the continued performance of Ichthruvi. I think the acceleration you're referring to is being driven by a few things. The first is physicians' desire to use the only near complete stabilizer on the market. Stabilization is the backbone of therapy in ATTR Centimeters, and near complete stabilization, along with the Truvy speed and showing separation from placebo, is attractive to patients and HCPs. They want something that's going to work quickly, and Truvy has shown that it can do that. And recently, as you heard from Neil in his original remarks, the real world evidence has backed all of these points up for both the treatment naive patients and the switch patients, and that's helping to drive our share upwards.

26:16 Yeah. Maybe the only thing I'd add there is the CRM TQR story, think, you know, you saw a bevy of papers both from us, but then importantly from others suggesting the numbers that I that I put forth, mid per deciliter increase associating with with pretty remarkable decreases in mortality downstream. And obviously, as a reminder, when we put patients on at Ramadan's following administration of tafamidis coming out of our phase three trial, you saw a three point four mg per deciliter increase. And everyone increased their serum TTR level. So it doesn't really matter how you measure it. You're just getting increases in serum TTR. And the question outstanding was never I don't know if Matt, if you'd agree with this whether or not Agrammaris is a better stabilizer. I think most people can understand that even if they can't understand a specific in vitro assay. And the bigger question was how much more is that buying me in terms of downstream results?

27:06 The serum TTR work was just the first part of that. I think you're going see a lot more of that in the coming twelve to twenty four months, really just because we we have enough patients now with enough duration that we can start to ask and answer those questions. Our next question comes from the line of Manny Faroohar with Leerink Partners. Please go ahead. Hey, guys. Thanks for the question. Congrats on results. In the aftermath of tafamidis IP evolution and some clarity on genericization of CAF, not of acromidis, Walk us through operationally how you think about the development and commercial strategy for Acoramidis into 2031, '32, and beyond. Yeah.

27:52 Hey, Manny. Thanks for the question. So the clarity on Windmass IP is is clearly a meaningful positive for Bridge and Atruby. You know, we now have at least six years of runway before generics, which is more than enough time to reach peak share. And and, obviously, this all materially reduces any tail risk we would have to the NPV of program. I don't think the resolution really changes our commercial strategy. We've always been focused on establishing a Truvia as the treatment of choice in ATTR Centimeters, given its differentiated profile, and we're executing against that. Think you heard both Neil and Max talk about the value of literature that we are producing, as well as all the commercial activities that we are undertaking to really reinforce that differentiation and drive share.

28:38 I guess what I'll say at the end is just, you know, we have shared our belief that a Truvy will be a $4,000,000,000 drug last year in our q one twenty five earnings call. I don't think we've ever been more confident in that estimate. I actually think if anything, there might be some room for potential upside. I think as Neil mentioned in his prepared remarks, our Truvy is likely to keep growing even after 2032, given the ecosystem and channel dynamics that that exists here with Part b. And and so that's kind of what's driving our confidence. So yeah. I think it's a it's a good thing for us. We've introduced the other bars on our evaluation. Yeah. Maybe maybe I'll add to that. I mean, I you know, I personally did think, Mania, we talked about it, that it would be $20.35. So, obviously, I was wrong on that. That is a little bit of a discount, but not not material, as I mentioned in my comments.

29:29 And the bigger thing is, like, you know, all of these differentiating studies that we're running, it is really starting to resonate with clinicians in addition to the fact that that's just programs are are superior. So, you know, I guess what your question is really alluding to is, like, will we run a double blind head to head? We still might. We reserve the we reserve the option to do that. Certainly, we've been excited to do that in the context of either TTR levels or NT proBNP. But but how we size, like, a hospitalization study is is it would be difficult if you look at the number of events. We're gonna have a strong look at the placebo arm of the upcoming aquatrisiran trials to really understand what those event rates look like in the context of clinical trials to see if there are some double blind head to head opportunities.

30:16 But there's nothing obvious right now, so let's continue doing the real world evidence studies, which I think are the best, honestly, characterization of sort of differential competitive dynamic. Our next question comes from the line of Biren Amin with Piper Sandler. Please go ahead. Yes. Hi, guys. Thanks for taking my questions. Can you walk us through the Board's decision to authorize the $500,000,000 share repurchase program and how you're thinking about balancing that against your investment in new launches and pipeline? And I guess what, if any, considerations are there for additional business strategic initiatives with this share repurchase program now being announced? Thanks. Scott, I can take that off. I mean, I think right now, the focus is on focused execution against the pipeline that we have right now. So we've got, in discussions with investors, ample growth that has not been valued in the context of this company to date. I mean, the LGMD2I launch that I referred to, the eighty eight one launch, the AECOM launch even is totality. Think, you know, we're we're projecting market share numbers well in excess of what typically a third mover gets in that space. And then you think about the consequential additional indications, both in terms of hypocon and importantly in terms of chronic hyperthyroidism that we're kicking off. And then we've got the the Canavan program. So, like, that constellation of activities is is more than more than enough to drive long term growth for any company. And that's kinda what we're

31:46 focused on. Do we can we fully finance all of that comfortably? And we feel like we can. And therefore, beyond that, what all we do with excess capital? And we think the best relative in terms of relative return way that we can deploy capital right now is into our own shares, just given the disconnect between intrinsic value and and where we're trading. So that's really what the discussion came down to. It's hard to you know, I know that I I know the normal way that a biotech would grow is say, well, who cares? Share price is low. Let's go ahead and dilute everyone and just keep going after science that we believe in. But that is not a reliable, sustainable, long term model in my belief, and nor is it one that we we intend to employ here at BridgeBio. Our next question comes from the line of Cory Kasimov with Evercore ISI.

32:39 Hey, good afternoon guys. Thanks for taking the question. Great to see all the ongoing progress. So I want to follow-up on this real world evidence that was referenced in both the press release and the prepared comments that reinforces attribute differentiation versus TAF. Can you kind of unpack what this real world data that you're seeing, how it compares with what was demonstrated in the clinical trial setting? Is anything different now than it was or just more of it? Thank you. Yes. It's pretty different because recall that we had a significant left shift in our clinical trial. Like, there was you know, our our our placebo outperformed the on drug arm of the tract. That so there's kinda no way for us to actually, apple to apples, go across, like, diuretic intensive kits. Oh, and by the way, like, even though with the use of diuresis and resident control meds and, you know, SGLTQI use in population, all of that stuff has changed pretty markedly. So it almost made it impossible, accepting the in trial comparisons we can make between tafamidis and acromidis with all the all of the available caveats there, where I mean, this is a reminder, acronyms outperformed its aminus in all aspects, which you did not see in HELIOS B. But I think real world evidence is the right way to do this within systems or across a constellation of systems that we know have a lot of integrity in terms of clinical studies. And here you're seeing things like, you know, what we've mentioned in terms of diuretic intensification. We certainly didn't look at downstream kidney effects like the, you know, the Nevada system did,

34:10 but but it's all resonant, I suppose, with the with the advantages that we think Atruvio has versus, you in terms of mortality and hospitalization. It's just nice to see it actually play out in in the real world. Our next question comes from the line of Salim Syed with Mizuho. Please go ahead. Hey, guys. Thanks for the question, and congrats on another great quarter. Just one from us maybe on infogratinib and PROPEL3. So since you guys have had that read, I'm sure you must have done some market share work or at least spoken to additional folks in the Aecon community both on the clinician side and family side. Just curious what the feedback has been there.

34:57 How has the additional feedback informed your expectations for the commercial opportunity? I believe you said previously, you sort of think about Aecon as being a $2,500,000,000 TAM and maybe HypoCon the same. Just curious if you have any other color there to offer on the commercial opportunity? Thank you. Yeah, thanks for the question. I think the feedback from the clinician caregivers made has been overwhelmingly positive. HCPs are telling us that they're constantly being asked by families when the oral is coming. Oakland families are on treatment today, but more importantly, those that stayed on the sidelines, which just as a reminder makes up about 70 to 80% of The US market. The consistent best in class profile is continuing to resonate with clinicians. They understand that AHP is best in class, the IT score is best in class, we have the most attractive safety profile, and importantly, proportionality, right? The proportionality data point is the one that's resonating most with clinicians because this is the only product that has a statin's result in proportionality in a three to eight age group population.

36:00 Which is a demonstration of how directly targeting FGFR3 impacts more than just height here in mental health. And on that note, we will be releasing more data on how Impregranam is benefiting more than just height in some medical conferences later this year, some of which have never been seen before in a fifty two week placebo controlled trial, so stay tuned there. Now ultimately, all this is to show that it really reinforces our belief that we will have a peak market share, actually more than 65% market share, as value of our market research here. Our next question comes from the line of Elimar with Barclays. Please go ahead. Hey guys, thanks for taking my question. Two from me. First on Limb girdle. So you submitted, the Limb girdle NDA very quickly, from our math about one hundred and fifty days from top line, which is very fast compared to average.

36:56 Can you walk us through where you stand on launch readiness and how you're preparing to get this drug into the hands of the limb girdle community from day one? And then a second question on the ATTR space. How are you thinking about what we will see from CardioTransform, specifically pralestepsin and the trial is very well powered, but what's the hazard ratio that you think could be competitive and how are you thinking about that? Hey, Ali, this is Tom. Good to hear from you. So I'm going to pass the one to Anna Wade here and then the CardioTransform Danielle. But first, I wanna say I'm really proud of her team for the quick turnaround on the NDA, and you can expect that level of efficiency from the next two as well. Over to Anna and then Danielle, the CARI to transform answer. Thanks for the question, Ellie, and thanks for the kind words, Tom. So, we're really excited. We have our commercial and sales leadership on board, and we're getting ready to have the sales reps hired later this year. We also now have our medical leadership in place, as well as a seasoned MSL team with neuromuscular and rare disease experience.

37:58 In Q1, our major catalyst was the NDA conference, as Neil mentioned, in March, where Doctor. Kathy Matthews, a leading KOL in the field, presented our Phase III interim analysis data, and we had incredibly positive feedback at the meeting about the compelling data package. Since NDA, we've heard about significant patient outreach to neuromuscular centres, and internally we have received many inbound inquiries from both patients and physicians. Our focus right now is driving awareness of the Phase three data, as well as emphasizing the importance of genetic diagnoses leveraging responsive testing programs that are currently available so that day one of launch we can be ready to get patients on the therapy. Our next question comes I think let let me address her her second question, which I think was on the cardio transform.

38:46 So, yeah, we we agree with you. It's a super well powered trial. I mean, obviously, the against the primary, it was good. And even in the subpopulations, like, if you take the same point estimate from from from Helios b on combo and you and you just take the z score, and then you say how many more patients would you need. It's, like, you know, it's two and a half times more to hit a p value of point o five or less, and they're pretty well powered for that. So I actually expect that they'll hit on almost everything that they're interrogating. And so then it comes back to, yeah, how do I cross drop compare? You know, how do I understand this knockdown technology? Part of that will be how much knockdown they get, and are they able to improve on the PK profile because, you know, I think that the reason that that task, you know, performs similarly to Ambutra or Boot in the Helios b trial has to do with the timing it takes for Boot to get to mean match knockdown. So, you know, it takes a lot longer than than I would have expected. So we'll see if that's the case with with with their drug. I think overall, honestly, cardio transform has more to do with the commercial dynamics with Alnylam than it does with us, especially given the combo data that I just told you about it.

39:54 I think people are gonna reach for stabilizers first line anyway, number one. Number two, I think when they're failing stabilizers, they're gonna want a better stabilizer onboard in in combination. So if that combo arm does hit, I don't see it having a meaningful super meaningful effect for us. Again, I mean, you know, I think from a biochemical standpoint, you always want to preserve the native tetramer. We're seeing more and more information about that. You know, I'm surprised people haven't been looking at the publicly available affairs database and what do things look like when you're knocking things down versus actually stabilizing and all consistent with the two twenty five thousand plus patient studies that we've seen out there suggesting the higher levels of serum TPR are better for you. But but I understand that in a short trial, those those signals aren't necessarily resolvable. But I think over the longer period of time, stabilizers will continue to be frontline. And then in combination, I think we'll we'll have a we'll have a pretty good stay there too. But that's kind of that's how we're thinking about it. We do think cardiotransform will be positive just given the patient numbers. On your hazard ratio question, I mean, obviously, we think the bar is relative risk reduction of forty two percent and risk reduction of fifty percent on hospitalization, which I suspect, if this study is consistent with the rest of the modern studies, are going be a vast majority of the events will be hospitalization, not mortality.

41:13 So I think that bar, fifty percent reduction in hospitalization, is kind of what I'll be looking for. Our next question comes from the line of Anupam Rama with JPMorgan. Please go ahead. Hey, guys. Thanks so much for taking the question, and and congrats on the quarter. Quick and count on one here. I know the NDA is on track here for the first half of this year. And then the press release highlighted nearly two thousand now identifiable patients with ICD-ten code. Can you give us an update about further patient identification efforts and how this sets up how we should all be thinking about the initial launch curve? Thanks so much.

41:59 Hey, good to hear from you. Yes, I would say that the foundation of everything that we're doing around patient identification is really awareness, awareness of the disease as an important distinct subset within hypoparra, and then of course, awareness of our drug and cholera and the wonderful effect it can have for patients. I think a major catalyst for awareness is going to be the upcoming presentation at ECE next week, followed by US presentations later in the year and then hopefully a very high impact publication as well. But in the background, I think there are some important tactics and strategies that we continue to employ. As you mentioned, the ICD-ten code is a huge advantage to us here. Many rare diseases don't have an ICD-ten code. We'll likely have one that's been in place for a couple of years already, so there's a good amount of data in that. That lets us take our analytics capabilities, put them on top of this, and really deploy our field based medical and commercial leadership in a more surgical way to go into the offices, spread awareness, and also make sure the patients they think they have are appropriately diagnosed with our sponsor genetic tests or other commercially available genetic tests.

43:09 And then third, I think this has been a bigger driver of identification that I would have thought is just family tracing. Makes sense when you consider this as a dominant condition, so there's fifty percent chance of passing on. So when we tend to find one person with this condition, if they look and go to a family event, we find out that many of them running at brothers, cousins, aunts and uncles also have the condition. So that's been a real valuable source of patient identification as well. So we'll continue all these efforts and accelerate them as we approach launch. Our next question comes from the line of Derek Archulo with Wells Fargo. Please go ahead. Hey there. Thanks for taking my questions and congrats on the progress. Just a follow-up on ifragatinib.

43:54 Some recent commentary and some of the early KPIs from the Ubile launch seem positive and maybe early validation of kind of this market expansion thesis. So just curious how you think about infographic profile versus the injectables and how this could further accelerate this market expansion potential? Thanks. Yeah, no, thanks, Eric. I think most of physicians and families are excited about the total package of different brands, right? Not just one thing. It starts with a 2.1 centimeter change in baseline HP, the largest effect shown across any of the three phase three, which was remarkable weight consistent across the age groups. Then of course, as mentioned earlier, the only statistic proven on personality is demonstration of the importance of directly engaging FGFR3. And then you have a differentiated safety profile, right, with no injection site reactions, no symptomatic hypertension, no hypertrichosis.

44:44 And I think the safety differentiation is further playing out given the increasing and concerning signals of SCIPI and femur fractures, which are both looking like potential CMV class effects. You know, the vote on top of this for us is being the daily oral. Based on historical benchmarks, we know that when oral enters a market with only injectables, it expands the market on average by three to four times at year five after launch. Ultimately, families here will have a choice of either three sixty five injections a year, 52 injections a year, or zero. And I know which one those families prefer. Our next question comes from the line of Paul Choi with Goldman Sachs. Please go ahead. Hi, thank you and good afternoon and thanks for taking the question.

45:31 Sticking with infogratinib, I want to ask with regard to the PROPEL infant and toddler study in patients who are newborns or up to two years old. Can you comment on your updated thoughts on enrollment timing and when that might potentially be completed in the wake of your positive results from the PROPEL study? And just how you think about timing for that potentially being completed and being added to the label? Thank you. Yeah, thanks for the question, Paul. Definitely, think there's a lot of excitement from sites and for families at the scene of the Phase III after the health three data, right? Just what we know from the field shows that the earlier you're intervening, the more likely to impact clinical outcomes. I think we've seen definitely a burst of excitement there. So we'll provide an update on timing probably later on once we have some more clarity once this program progresses.

46:24 Our next question comes from the line of Andrew Tully with Jefferies. Please go ahead. Hey. Thanks for all the updates. Congrats on the execution. I have a bigger picture question for you guys on your broader pipeline. Now that you have succeeded across four major programs all the way through Phase three, as investors think about the sustainability of your R and D engine, maybe talk about how you're currently thinking about the next wave of development beyond your portfolio and how much you're open to adding more to the pipeline in the near term and what indication areas you could be interested in? Thank you. Yeah. Thanks for the question. I think right now, as I think, you know, a lot of our comments and and actions have have been, well, we've been consistent with we're very focused on executing the opportunity in front of us. It's not often that a biotech will launch three different products and three different indication settings alongside a pretty competitive market at the same time, and that's gonna take, certainly, against our lean backbone, all all of the all of the focus that that we have.

47:32 You know, I I also mentioned earlier that we have pretty significant additional opportunities associated with every single one of our drug products, including some that we haven't talked about vis a vis a vis. So I actually think that there's some pretty interesting stuff to do. We have an internal pipeline, obviously, prosecuting programs at ADPKD, eliminating polymyopathy, and the complete or antibody program in ATTR cardiomyopathy. So that's additionally programs that are very, very capital efficient, but programs that we have an eye on today. And then we've got backup programs against all of our current pipeline programs so that we can do what's right for for the patient and physician community to continue to serve that as long as possible. So all of those things put together, I would say, represent the menu of activities that we're interested in in the near term. Obviously, we're students of the genetic disease space.

48:26 BridgeBio has a significant stake in another company called BONDYLLA BBIO, which is really kind of one of our sister companies. And that has 17 programs that I think we've gone through, ranging from phase two all the way back to the preclinical setting. And it has a very, very exciting slate of small molecules, ASOs, antibodies, all targeting well described genetic conditions at their source. And so I would say that we're happy for that to be sort of an off balance sheet R and D exercise for now, as is BridgeBio Oncology Therapeutics, and really to focus on what we need to focus on here, which is continued prosecution of our pipeline programs, delivery of these important medicines to patients, and ultimately the capturing of the value that we have created for the investors that have passed us for many years.

49:14 Our next question comes from the line of Daniel Brill with Truist. Please go ahead. Hey guys, thanks for the question and congrats on the great quarter. Neil, I believe you mentioned in your prepared remarks that there were 6,100 new patient starts across the class in the quarter. If I recall correctly, this represents the pretty meaningful step up from prior quarters where I think it was more in the 4,000 new patients range. Just curious what's driving the step up here. And moving forward, how should we think about the size of the quarterly patient pool that you're actively competing for? Thank you. Yeah. Sure. I mean, I think I think this market continues to grow somewhere between, like, you know oh, I think our internal numbers are somewhere between 5,006, you know, in in that range a quarter in terms of these new patient new patient starts or new patients to to brand.

50:13 So, actually, I don't think we have 4,500 for the last quarter. I think it was it was it was above 5,000. Like, a little bit of this math has to do with, like, us guessing for our competitors what the inventory holdback was or what the inventory buys were and and things of that nature. So can never get it fully right. We can get, obviously, our own patient numbers fully right. But that but that does suggest, yeah, continued growth. I mean, will it continue to grow? I think so. Obviously, there's two two hundred fifty thousand patients with HDR cardiomyopathy at the low end in The US, and I think we're doing a better job of three things. One is making sure that the the algorithms are are in easy MRs so that people take a look for these patients. You know, the the there's all the Tracer AI stuff that we've been doing, other algorithms that individual health care systems have been putting forth to just get people to think, ah, maybe this is a a DVR patient. So that's one. Second is driving genetic testing into variant heavy populations. That's been that's been helpful as well. And third and probably best is just broad physician awareness and education through speaker bureaus, really getting out into the capital of practices and the community practices to educate them more. So all of that's positive. I'd say on the negative side, we've heard quite a bit about this PYP shortage, the technicians can, you know, one of the ways that you can do the scans to get a definitive diagnosis alongside the ELISA assay.

51:40 So that, we have to keep an eye on. And, you know, we've heard about that before. Like, in 2025, we've heard about that, I think, in the second or third quarter. So, know, one of the big quarters and the market continues to grow. But we'll keep an eye on that. That's resolvable. There's three major suppliers of that. And then I think I expect in years going forward, we shouldn't see much much more of this sort of this this supply chain iteration around PYP availability. Yeah. I guess long story short, I I believe that you should see felt like like, I think our report put out a nice analysis of this three years ago or so. It was like, should see super linear growth in identification given the number of patients that we believe have HDL cardiomyopathy coupled with the number of sponsors in the playing field and the availability of reasonable testing, I expect that trend to that positive trend to continue with some error bars quarter to quarter.

52:38 Our next question comes from the line of Jason Zemanski with Bank of America. Please go ahead. Good afternoon. Congrats on the great progress and thanks for taking our question. Maybe one more on Incalired, if we may. As you look beyond the ADH1 opportunity, of the broader chronic hypoparathyroidism opportunity, How are you thinking about Incalibrate's positioning, I guess relative to the parathyroid hormone replacement therapies? Is there a particularly attractive subgroup to target or are you looking at sort of the broader opportunity as a whole? And then maybe if you could talk about some of the pricing implications of pursuing a market that maybe looks a little bit like 25,000 patients in The U. S. And EU versus two hundred thousand? Thanks.

53:25 Yeah. Hey, Jason. It's great to hear from you, and and thank you for the question. We look forward to seeing you next week at the conference. So in terms of in pallid and chronic hyperparathyroidism, when we did our market research, it's really three things which drove our excitement about the opportunity. The first is that this will be the first oral option available in in this chronic setting. And so the ability to give patients freedom from injection site reactions and all the pain that comes with it is something that resonates very well, I would say. The second thing is, if you look at the current options available, you do see an effect in terms of blood calcium normalization, but you don't really see that effect on urine calcium normalization. And I think within CALIDEX we have a very unique profile where we could normalize potentially both blood and urine calcium.

54:15 We saw that in our albeit small phase two trial where we had around eighty percent of the patients normalizing both blood and urine calcium, these were patients who were very sick and did not have the at our gland or any amount of the hormone. And then really the third thing is that there is a potential safety risk in terms of bone absorption from giving TTH at at at high levels for the whole day. And so I think we could completely avoid that. And I think actually the eighty eight one read out significantly the risk that ox profile for the calorie. And so I think that those three things, oral, urine calcium normalization, and potential benefit on safety is really what why we think we can compete and and and get a reasonable share even in the chronic avapara market, obviously, assuming that the trial works.

55:08 Our next question comes from the line of Shan Lehmann with Morgan Stanley. Please go ahead. Hi. This is Morgan on for Shan. Thanks for taking our question. Can you just remind us specifically for invagradinib and achondroplasia, what kind of, if any, commercial preparations are taking place from BridgeBio? You. Thanks for the question. I think we've done a lot to really build strong commercial and medical leadership here, right, bringing on for both sides of the business. We usually have experience in both second and third's market with security data, especially with experience kind of launching an oral. We've also had a lot of experience with firms, groups with skilled dyslexia experience as well. So ultimately, I think right now we're trying to make sure that we get the word out, just in the leading geneticists and ANCs, but also to the broader community of pediatric endocrinologists who are really excited about having an oral option, especially for families who have, you know, if they're not seeing have these super specialized centers of care, are more interested in having something that's easier for families to administer as well. So a lot of preparation going on that front.

56:14 Yeah. Think to remember, we have a lot of the teams in place from the Atruvio launch that can also help with the future launches for all of the indications. Think about market access with the payers, the pharmacies. These are all the same individuals, and we have relationships with all of those people and, are able to launch quickly, I think, as a result of that and get access and coverage. Our next question comes from the line of John Boyle with William Blair. Please go ahead. Hi, team. Thanks so much for taking our question and congrats on a strong quarter. So patient advocacy groups for achondroplasia seem to have a pretty big voice in the indication. So wondering if you've had any interactions with them and if you could speak to how infogrutinib profile is resonating there.

57:03 Yeah. Again, thanks thanks for the question. I think that's just been a core tenet of how we've been developing drugs since the very beginning. You know, we've been working alongside absolute groups both in The United States and internationally on making sure that their input and voice is implemented in our development program and how we think about endpoints. And for us, being able to target FGFR3 directly addresses their concerns of being able to look at not just height outcomes, but health outcomes as well, which is something we expect to play out in the longer term in our clinical extension program. And I think they've been really wonderful partners with us and we anticipate that persisting through commercialization and launch as well. Thank you. And ladies and gentlemen, that concludes our Q and A session. I will now turn the call back over to the BridgeBio team for closing remarks.

57:49 Thank you, everyone, for your questions today. We really appreciate your interest and look forward to updating you again next quarter. Ladies and gentlemen, that concludes our conference call. You may now disconnect your lines. Have a pleasant day.