Good afternoon, I will be your conference operator today. All lines have been placed in mute to prevent any background noise. After the company's remarks, there will be a question and answer session. If you would like to ask a question, please press star followed by the number one on your telephone keypad. And if you would like to withdraw your question, press star one again. Thank you. Before we begin, I would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities law, 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 this risk and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today. 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, thank you for joining BridgeBio Pharma's first quarter 2026 earnings call. I am Chinmay Shukla, Senior Vice President, Strategic Finance. With me are Neil Kumar, our CEO; Matt Outten, our Chief Commercial Officer; and Tom Trimarchi, 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. Following our prepared remarks, we will open the call for questions. For the Q&A session, we will be joined by Ananth Sridhar, Anna Wade, and Justin To, who will lead our programs with encaleret, BBP-418, and ensetrezumab respectively. With that, I'll turn it over to Neil.
Thanks, Chinmay. 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 want to spend the bulk of my time today talking about three things. The first is the Attruby franchise, and I want to talk about our continued commercial momentum there and how we think about clinical differentiation. Importantly, these two things, plus the economics associated with the RD orphan drug channel, underpin our confidence that Attruby will continue to grow even past 2032. The second thing I want to discuss is launch readiness against the three exciting first-in-class or best-in-class brands we have in ADH1, LGMD2I, 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 3 approved products, with hopefully 3 more to come, the ability to take on post-phase III regulatory submission activities at very high quality. 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 tune into these calls to hear. 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.
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. By the way, our activities across the BridgeBio ecosystem show that there are many more of these RD opportunities out there. This model is reliant on capturing the value of the work for investors, which is why today I will be discussing a share buyback program that will commence immediately. Let me begin my comments by talking about Attruby.
As many of you have read in the press release, we've had $180.6 million of Attruby sales in U.S. Attruby net product revenue this quarter, which represents a 24% growth from the last quarter and a 392% growth year-over-year, and is consistent with the brand globally becoming a blockbuster in 2026.
Our focus continues to be on winning in the front line, where 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 amyloid 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 Attruby 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 front line, our major competition continues to be Pfizer, and our best understanding of our share is that it has grown from the medRxiv share I quoted at the JPM talk of 25% even furthermore, but still remains behind what Pfizer has been able to accomplish in the front line. 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. 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 that higher levels of serum TTR associated with lower levels of mortality at 30 months. As a reminder, every 1 mid per deciliter of incremental increase in serum TTR seems to lead to a 5% decrease in mortality risk at 30 months, meaning a more potent stabilizer, and we do not hear from many physicians quibbling with the fact that Attruby is a more potent stabilizer, it is, should lead to better outcomes for the patients that we serve. Building on that, we are now beginning to explore and are confident in the outperformance of acoramidis versus tafamidis in the real-world setting.
There were only really 2 real-world evidence studies reported to date, survival studies done in Columbia and by Dr. Masri that showed outperformance of acoramidis both. Those were comparing our trial data. 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 SCAI, an independent real-world evidence study presented by the Valley Health System of Nevada revealed statistically significant outcome improvements associated with acoramidis as compared to tafamidis. Building on this, we have a study in medRxiv that we will publish shortly in a major journal showing that Attruby reduces diuretic intensification by 43% as compared to tafamidis. We intend to continue studying and publishing on Attruby'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 JP Morgan 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 ATTRUBY as opposed to the other stabilizers and knockdowns in the space. We continue to present and publish on acoramidis 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 acoramidis at month 54, including a remarkable statistically significant risk reduction of 45% in all-cause mortality with a P value of less than 0.0001 and a 49% reduction in cardiovascular mortality, again, with a similar P value versus placebo tafamidis or to acoramidis. All right. I'd like 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 data to NDA submission in 155 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 that our data generated, not only within the LGMD2I community, but more broadly, given the striking results associated with BBP-418 suggest that functional improvement is possible when targeting well-described conditions at their source. Given the already 500 or so genetically confirmed patients in the U.S. 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 ADH1, I'll be leaving from here to a very similar gathering, a top-line presentation of our CALIBRATE phase III 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 U.S. that continue to identify new patients with relatively high yield.
Although we are launching at a time when a vast majority of patients with ADH1 have not been identified yet, the combo of genetic testing, ICD-10 codes, and broad disease awareness education helps buttress 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 hypoparathyroidism 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, 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 3 data set at a medical conference in the second half of 2026. Early commercial research here suggests unaided awareness in excess of 40% amidst the prescribing physician community, which for those of you who are commercial experts know is a very high starting point and certainly higher than what we've seen before in our own portfolio. Finally, I want to 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 point. The reason for that is because if we capture value, more capital flows into drug development over time and more patients get served by us and others employing our decentralized, diversified model. Unfortunately, at this moment, we have not adequately captured value for the investors we serve, given the large disconnect between our NPV per share and our firm's intrinsic value.
Even with the revision of VYNDAMAX's entry from 2035 to mid-2031 or early 2032, our intrinsic value remains markedly higher than what we've been able to get the shares to trade to today for investors. To that end, the board has authorized a $500 million 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.
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. 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 credible 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. Q1 was another strong quarter for Attruby, delivering an impressive 24% increase in net sales from Q4 and a 392% year-over-year increase from Q1 2025. Growth was driven by our existing and expanded sales teams accelerating new patient starts and first-line share gains. 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 2025, 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 authorizations reauthorization dynamics has been a topic of industry discussion this quarter, and I want to address them directly. Attruby 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. In 2025, the average co-pay for ATTRUBY 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, those people make sure that any patient who wants a near-complete stabilizer can get ATTRUBY and importantly, can stay on ATTRUBY. Turning to our pipeline, we are encouraged by early indicators across our three anticipated near-term launches in LGMD2I/R9, ADH1, and achondroplasia. In LGMD2I/R9, we are entering a disease area where no approved therapy exists.
We've onboarded a commercial leadership team and have set up a specialized patient identification and field reimbursement infrastructure. Our goal is simple: find every patient who can benefit and be ready to serve them from day one of approval. In ADH1, our claims analysis has already identified nearly 2,000 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. Encaleret would be the first medication to target the disease mechanism directly and it's orally administered. 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. Infigratinib 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.
For families seeking an alternative to injectables or returning to treatment after a negative experience, the clinical profile and route of administration of infigratinib is very compelling. To summarize, Q1 continues to reflect a durable growth trajectory for Attruby 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 2026. Our commentary will focus on GAAP financials, unless otherwise noted. Total revenues for the first quarter of 2026 were $194.5 million compared to $116.6 million for the same period in 2025. The $77.9 million increase was primarily driven by a $143.9 million increase in ATTRUBY net product revenue. ATTRUBY net product revenue in the quarter was $180.6 million compared to $36.7 million for the same period last year. Royalty revenue increased by $9.3 million to $9.5 million, primarily earned from net product sales of BEYONTTRA in Europe and Japan.
License and services revenue was $4.4 million compared to $79.7 million for the same period last year. The decline reflects the recognition of a one-time $75 million regulatory milestone earned the prior year. Total operating expenses for the first quarter of 2026 were $290.5 million compared to $218.4 million for the same period last year. The $72.1 million increase reflects deliberate and disciplined investment in ATTRUBY and preparations for three upcoming launches. SG&A expenses were $163.9 million, an increase of $57.5 million compared to the same period last year, reflecting measured investment in our commercial activities.
R&D expenses were $126.6 million, an increase of $15.2 million driven by investments in medical affairs and CMC in support of our next three launches. Turning to the operating line. In the first quarter, we recorded a $106 million operating loss. For the last five quarters, our loss from operations has narrowed by more than 50% due to OpEx discipline paired with strong execution on ATTRUBY. 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 ATTRUBY launched.
Looking ahead, we expect the trend in loss from operations to flatten over the next 2 quarters as we ramp up launch readiness activities for the next 3 products and continue narrowing towards the end of this year to 2027 as we transition to a P&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 $940.2 million in cash equivalents, and marketable securities, compared to $587.5 million at the end of last year. We believe our current cash position provides us with significant runway to fund our operating activities, advance our 3 late-stage programs towards approval and launch, and continue to invest in true exploratory growth, all while maintaining financial discipline we've demonstrated to date.
With that, I'll turn the call back over to Chinmay.
Thank you, Neil, Matt, and Tom. Operator, please open the line for questions now.
Thank you. Ladies and gentlemen, we will now begin the question and answer session. At this time, I would like to remind everyone in order to ask a question, please press star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again. In the interest of time, we kindly ask everyone to limit themselves to 1 question only. We will pause for a moment to compile the Q&A roster. 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, can you guys talk about what's driving the continued ATTRUBY acceleration and specifically what you're seeing in those treatment-naive patients? Thank you very much.
Hey, this is Matt. I'll take that one. Thanks for the question. We're definitely excited about the continued performance of ATTRUBY. 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-CM. Near complete stabilization, along with ATTRUBY speed and showing separation from placebo, is attractive to patients and HCPs. They want something that's going to work quickly. ATTRUBY has shown that it can do that. 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 switch patients. That's helping to drive our share upwards.
Maybe the only thing I'd add there is, the serum TTR story, you know, you saw a bevy of papers, both from us, importantly from others. You've got the numbers that I put forth, the mg per deciliter increase associating with pretty remarkable decreases in mortality downstream. You know, obviously, as a reminder, when we put patients on acoramidis following administration of tafamidis coming out of our phase III trial, you saw a 3.4 mg per deciliter increase. Everyone increased their serum TTR levels. It doesn't really matter how you measure it. You're just getting increases in serum TTR. The question outstanding was never, I don't know, Matt, if you'd agree with this, whether or not acoramidis is a better stabilizer.
I think most people can understand that even if they can't understand a specific in vitro assay. The bigger question was, how much more is that buying me in terms of downstream results? The serum TTR work was just the first part of that. I think you're gonna see a lot more of that in the coming 12 to 24 months, really just because 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 Mani Foroohar with Leerink Partners. Please go ahead.
Hey, guys. Thanks for the question. Congrats on the results. In the aftermath of the tafamidis IP evolution and some clarity on genericization of past, not acoramidis, walk us through operationally how you think about the development and commercial strategy for acoramidis into 2031, 32 and beyond.
Yeah. Yeah. Hey, Mani. Thanks for the question. The clarity on Sanofi's IP is clearly a meaningful positive for Bridge and ATTRUBY. You know, we now have at least 6 years of runway before genetics, which is more than enough time to reach peak share. Obviously, this all materially reduces any tail risk we would have to the NPV of the program. I don't think the resolution really changes our commercial strategy. We've always been focused on establishing ATTRUBY as the treatment of choice in ATTR-CM, given its differentiated profile, and we are executing against that. I think you heard both Neil and Matt talk about the bevy of literature that we are producing as well as all the commercial activities which we are undertaking to really reinforce that differentiation and drive share.
I guess what I'll say at the end is just, you know, we've shared our belief that ATTRUBY will be a $4 billion drug last year in our Q1 2025 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, ATTRUBY is likely to keep growing even after 2032, given the ecosystem and channel dynamics that exist here with Part D. That's kind of what's driving our confidence. Yeah, I think it's a good thing for us. We've reduced the error bars on our evaluation.
Yeah. Maybe I'll add to that. I mean, I, you know, I personally did think, Mani, and we talked about it, that it would be 2035. Obviously I was wrong on that. That is a little bit of a discount, but not material, as I mentioned in my comments. 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 the access programs are superior. 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 option to do that. Certainly, we've been excited to do that in the context of either TTR levels or NT-proBNP.
How we size a hospitalization study is difficult if you look at the number of events. We're gonna have a strong look at the placebo arm of the upcoming eplontersen trial 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. You know, 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 dynamics.
Our next question comes from the line of Biren Amin with Piper Sandler. Please go ahead.
Yeah, hi guys. Thanks for taking my questions. Can you walk us through the board's decision to authorize the $500 million share repurchase program and how you're thinking about balancing that against your investment in new launches and pipeline? I guess what, if any, considerations are there for additional business strategic initiatives with this share repurchase program now being announced? Thanks.
Yeah, I can kick that off. I mean, I think right now the focus is on focused execution against the pipeline that we have right now. You know, 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 ADH1 launch, the achon launch even in its totality. I think, you know, we're projecting market share number is well in excess of what typically a third mover gets in that space. You think about the consequential additional indications both in terms of hypoparathyroidism and importantly in terms of chronic hypoparathyroidism that we're kicking off. We've got the Canavan program.
Like, that constellation of activities is more than enough to drive long-term growth for any company, and that's kind of what we're focused on. Can we fully finance all of that comfortably? We feel like we can. Therefore, beyond that, what ought we do with excess capital? We think the best relative, you know, 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 where we're trading. That's really what the discussion came down to. You know, 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. That is not a reliable, sustainable long-term model in my belief, and nor is it one that we intend to employ here at BridgeBio.
Our next question comes from the line of Cory Kasimov with Evercore ISI.
Hey, good afternoon, guys. Thanks for taking the question. Great to see all the ongoing progress. I wanna follow up on this real world evidence that was referenced in both the press release and the prepared comments that reinforces ATTRUBY's differentiation versus taf. Can you kind of unpack, you know, 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.
It's pretty different because recall that we had a significant left shift in our clinical trial. Those, you know, our placebo outperformed the on-drug arm of ATTR-ACT. There, there's kinda no way for us to actually apples to apples go across like diuretic intensive case. By the way, like even the use of diuresis and, renocontrol meds and, you know, SGLT2i use in this population, all of that stuff has changed pretty markedly. It almost made it impossible, excepting the in-trial comparisons we can make between tafamidis and acoramidis with all of the available caveats there, where, I mean, just as a reminder, acoramidis outperformed tafamidis in all aspects which you did not see in HELIOS-B.
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. Here you're seeing things like, you know, what we've mentioned in terms of diuretic intensification. We certainly didn't look at, you know, downstream kidney effects like the, you know, the Nevada system did. But it's all resonant, I suppose, with the advantages that we think ATTRUBY has versus tafamidis in terms of mortality and hospitalization. It's just nice to see it actually play out 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 infigratinib and PROPEL 3. You know, 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 achon community, both on the clinician side and family side. Just curious what the feedback has been there. How has the additional feedback informed your expectations for the commercial opportunity? I believe you said previously you sort of think about achon as being a $2.5 billion TAM and maybe hypoparathyroidism the same. Just curious if you have any other color there to offer on the commercial opportunity. Thank you.
Yeah. Thanks much for the question, Salim. I think the feedback from the clinician and caregivers may have been overwhelmingly positive. You know, HCPs are telling us that they're constantly being asked by families when the oral is coming. You know, both from families who are on treatment today, but more importantly, those that have stayed on the sidelines, which just as a reminder makes up about 70%-80% of the U.S. market. You know, the consistent best-in-class profile is continuing to resonate with these clinicians. You know, they understand that the AHV is best in class, the IT score is best in class. We have the most attractive safety profile and importantly, on proportionality, right?
The proportionality data point is the one that's resonating most with clinicians, because this is the only product that has a stat sig result in proportionality in a 3-8 age group population. This, which is a demonstration of how directly targeting FGFR3 impacts more than just height here in skeletal health. On that note, we will be releasing more data on how infigratinib is benefiting more than just height in some medical conferences later this year, some of which has never been seen before in a 52-week placebo-controlled trial. Stay tuned there. Now, ultimately, all this is to show that it really reinforces our belief that we will have a peak market share, potentially more than 68% market share, as validated by our market research here.
Our next question comes from the line of Ellie Merle with Barclays. Please go ahead.
Hey, guys. Thanks for taking my question. Two from me. First, Limb-girdle. You submitted the Limb-girdle NDA very quickly, from our math, about 150 days from top line, which is very fast, compared to average. 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 1? A second question on the ATTR space. How are you thinking about what we will see from CARDIO-TRANSFORM, specifically trial stat sig? You know, 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, Eliana Merle. This is Tom Trimarchi. Good to hear from you. I'm gonna pass the limb-girdle one to Anna Wade here and then the CARDIO-TRANSFORM to Neil Kumar. First I want to say I'm really proud of our 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 Wade and then to Neil Kumar with the CARDIO-TRANSFORM answer.
Thanks for the question, Eliana Merle, and thanks for the kind words, Tom . Yeah, we're really excited. We have our commercial and sales leadership on board. 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. In Q1, our major catalyst was the NDA conference, as Neil Kumar mentioned in March, where Dr. Kathleen Matthews, a leading KOL in the field, presented our phase II interim analysis data. We got incredibly positive feedback at the meeting about the compelling data package. Since NDA, we've heard about significant patient outreach to neuromuscular centers, and internally, we have received many inbound inquiries from both patients and physicians.
Our focus right now is driving awareness of the phase III data, as well as emphasizing the importance of genetic diagnoses, leveraging responses, 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.
Yeah. On the Cardio, I think let me address your second question, which I think was on the CARDIO-TRANSFORM. Yeah, we agree with you. It's a super well-powered trial. I mean, obviously against the primary, it looks good. Even in the subpopulations, like, if you take the same point estimate from HELIOS-B on combo and you just take the Z-score and then you say, "How many more patients would you need?" It's like, you know, two and a half times more to hit a P value of 0.05 or less, and they're pretty well powered for that. I actually expect that they'll hit on almost everything that they're interrogating. It comes back to, how do I cross-trial 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 the reason that taf, you know, performed similarly to AMVUTTRA or vutrisiran in the HELIOS-B trial has to do with the timing it takes for vutrisiran to get to mean max knockdown. You know, takes a lot longer than I would've expected. We'll see if that's the case 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. I mean, 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 on board in combination. 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 FAERS database and what do things look like when you're knocking things down versus actually stabilizing and all consistent with the 225,000-plus patient studies that we've seen out there suggesting that higher levels of serum TTR are better for you. I understand that in a short trial, those signals aren't necessarily resolvable.
I think over the longer period of time, stabilizers will continue to be frontline and then in combination, I think we'll have a pretty good stay there too. That's kinda that's how we're thinking about it. We do think CARDIO-TRANSFORM 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 42% and risk reduction of 50% on hospitalization, which I suspect if this study is consistent with the rest of the modern studies, are gonna be a vast majority of the events will be hospitalization, not mortality. I think that that bar, 50% reduction in hospitalization is kinda what I'll be looking for.
Our next question comes from the line of Anupam Rama with JP Morgan. Please go ahead.
Hey, guys. Thanks so much for taking the question and congrats on the quarter. Quick on encaleret 1 here. Know the NDA is on track here for the first half of this year. The press release highlighted nearly 2,000 now identified identifiable patients with ICD-10 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.
Hey, good to hear from you. 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 hypoparathyroidism, and then of course, awareness of our drug, encaleret, and the wonderful effect it can have for these patients. I think a major catalyst for awareness is going to be the upcoming presentation at ECE next week, followed by U.S. presentations later in the year, and then hopefully a very high impact publication as well. In the background, I think there's some important tactics and strategies that we continue to employ. First, as you mentioned, the ICD-10 code is a huge advantage to us here. Many rare diseases don't have an ICD-10 code.
We're lucky to 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. Third, I think this has been a bigger driver of identification than I would have thought is family tracing. Makes sense when you consider this is a dominant condition, so there's a 50% chance of passing on.
When we tend to find 1 person with this condition, if they look and go to a family event, we find out that many of them, you know, brothers, cousins, aunts and uncles also have the condition. That's been a real valuable source of patient identification as well. We'll continue all these efforts and accelerate them as we approach launch.
Our next question comes from the line of Derek Archila with Wells Fargo. Please go ahead.
Hey there. Thanks for taking my questions, and congrats on the progress. Just a follow-up on infigratinib. You know, some recent commentary and some of the early KPIs from the ubiwell launch seem positive and maybe, you know, early validation of kind of this market expansion thesis. Just curious how you think about infigratinib's profile versus the injectables and how this could further accelerate, you know, this market expansion potential. Thanks.
Thanks, Derek. You know, I think ultimately physicians and families are excited about the total package of infigratinib, right? Not just one thing. It starts with a 2.1 centimeter change in baseline HB. You know, the largest effects shown across any of the three phase IIIs, which was remarkable weight consistent across the age groups. Of course, as mentioned earlier, the only 56 improvement on personality, a demonstration of the importance of directly engaging FGFR3. You have a differentiated safety profile, right? With no injection site reactions, no symptomatic hypertension, no hypertriglycerides. I think the safety differentiation system is further playing out given the increasing and concerning signals of SCFE and femur fractures, which are both looking like potential CMP class effects. You know, the bow 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 3 to 4 times at year 5 after launch. Ultimately, the families here will have a choice of either 365 injections a year, or 52 injections a year, or 0, and I know which one most families would 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. Sticking with the infigratinib, I want to ask with regard to the PROPEL Infant & Toddler study in patients who are newborns or up to 2 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? Just, you know, how you think about timing for that potentially being completed and being added to the label. Thank you.
Yeah. No, thanks for the question, Paul Choi. Definitely, I think there's a lot of excitement from sites and from families after seeing the phase III, PROPEL 3 data, right? Just what we know from the field shows that the earlier you intervene, the more likely to impact clinical outcomes. I think we've seen definitely a burst of excitement there. You know, we'll provide an update on timing probably later on once we have some more clarity once this program progresses.
Our next question comes from the line of Andrew Tsai 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 4 major programs all the way through phase III, as investors think about the sustainability of your R&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 actions have obviously 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 in three different indication settings alongside a pretty competitive market at the same time. That's going to take, certainly against our lean backbone, all of the focus that we have. You know, 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 Attruby. I actually think that there's some pretty interesting stuff to do.
We have an internal pipeline, obviously prosecuting programs at ADPKD, Elon and Adality cardiomyopathy, and the depleter antibody program in ATTR cardiomyopathy. That's additionally, you know, programs that are very, very capitally efficient but programs that we have an eye on
To date, we've got backup programs against all of our current pipeline programs so that we can do what's right for the patient and physician community that continue to serve us out as long as possible. 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. BridgeBio has a significant stake in another company called GondolaBio, which is really kind of one of our sister companies, that has 17 programs that I think we've gone through, ranging from phase II all the way back to the pre-clinical setting. It has a very, very exciting slate of small molecules, ASOs, antibodies, all targeting well-described genetic conditions at their source.
I would say that we're happy for that to be sort of an off-balance sheet R&D exercise for now, as is BridgeBio Oncology Therapeutics and to really focus on what we need to focus on here, which is continued prosecution of our pipeline program and delivery of these important medicines to patients, and ultimately the capturing of the value that we have created for the investors that have backed us for many years.
Our next question comes from the line of Danielle 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. 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, I think our internal numbers are somewhere between 5,000 and 6,000, you know, in that range, a quarter in terms of these new patient starts or new patients to brand. Actually, I don't think we have 4,500 for the last quarter. I think it was above 5,000. 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 things of that nature. Can never get it fully right. We can get obviously our own patient numbers fully right. That does suggest, yeah, continued growth.
I mean, will it continue to grow? I think so. Obviously, there's 250,000 patients with ATTR cardiomyopathy at the low end in the U.S., and I think we're doing a better job of 3 things. One is making sure that the algorithms are in eDMRs so that people think to look for these patients. You know, there's all the tracer AI stuff that we've been doing, other algorithms that individual healthcare systems have been putting forth to just get people to think, "Maybe this is a TTR patient." That's 1. Second is driving genetic testing into variant-heavy populations. That's been helpful as well.
Certainly probably best is just broad physician awareness and education through speaker bureaus, really getting out into the capitated practices and the community practices to educate them more. All of that's positive. I'd say on the negative side, we've heard quite a bit about this PYP shortage, the technetium scan. One of the ways that you can do the scans to get a definitive diagnosis alongside the ELISA assay. That we have to keep an eye on. We've heard about that before. Like in 2025, we heard about that, I think, in the 2nd or 3rd quarter. One of the mid quarters and the market continued to grow.
We'll have to keep an eye on that. That's resolvable. There's 3 major suppliers of that. I expect in years going forward, we shouldn't see much more of this sort of this supply chain iteration around PYP availability. I believe that you should see Evercore put out a nice analysis of this 3 years ago or so. It's like you should see super linear growth in identification given the number of patients that we believe have ATTR cardiomyopathy, coupled with the number of sponsors in the playing field and, you know, the availability of reasonable testing.
I would expect that positive trend to continue with, you know, with some error of ours quarter to quarter.
Our next question comes from the line of Jason Zemansky with Bank of America. Please go ahead.
Good afternoon. Congrats on the great progress, and thanks for taking our question.
Yeah.
Maybe 1 more on encaleret, if we may. As you look beyond the ADH1 opportunity to sort of the broader chronic hypoparathyroidism opportunity, how are you thinking about encaleret'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? Maybe if you talk about some of the pricing implications of pursuing a market that, you know, maybe looks a little bit like 25,000 patients in the U.S. and EU to, you know, versus 200,000. Thanks.
Yeah. Hey, Jason. It's great to hear from you, and thank you for the question. We look forward to seeing you next week at the conference. In terms of encaleret and chronic hypoparathyroidism, 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 this chronic setting. 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, you don't really see that effect on urine calcium normalization.
I think with encaleret, we have a very unique profile where we could normalize potentially both blood and urine calcium.
All these small phase II trials where we had, you know, around 80% of the patients normalizing both blood and urine calcium. These were patients who were very sick and did not have the thyroid gland or any amount of the hormone. The third thing is that there is a potential safety risk in terms of bone resorption from giving PTH at high levels for the whole day. I think we could completely avoid that. I think actually the ADH1 readout significantly de-risks the tox profile for encaleret.
I think that those three things, oral urine calcium normalization and potential benefit on safety is really why we think we can compete and get a reasonable share even in the chronic hypoparathyr market, obviously assuming that the trial works.
Our next question comes from the line of Sean Laaman with Morgan Stanley. Please go ahead.
Hi, this is Morgan on for Sean. Thanks for taking our question. Can you just remind us specifically for infigratinib and achondroplasia what kind of, if any, commercial preparations are taking place from BridgeBio? Thank 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, leadership has experience in both second and third market with security data, especially with experience kind of launching oral. We've also brought a lot of experience with certain groups with skeletal dysplasias experience as well. Ultimately, I think right now we're trying to make sure that we get the word out, not just to the leading geneticists and AMCs, but also to the broader kind of community pediatric endocrinologists who are really excited about having an oral option, especially for families who have, you know, if they're not seeing kind of these super specialized centers of care, are more interested in having something that's easier for families to administer as well. A lot of exploration going on that front.
Yeah, I think to remember we have a lot of the teams in place from the Attruby 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. Patient advocacy groups for achondroplasia seem to have a pretty big voice in the indication. Wondering if you've had any interactions with them, and if you could speak to how the infigratinib profile is resonating there.
Thanks for the question. I think that's just been a core tenet of how we've been developing the drug since the very beginning. We've been working alongside advocacy groups, both in the U.S. and internationally, on making sure that their input and voice is implemented in our development program and how we think about endpoints. 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 post-approval extension program. I think they've been really wonderful partners with us, and we anticipate that persisting through commercialization and launch as well.
Thank you. Ladies and gentlemen, that concludes our Q&A session. I will now turn the call back over to the BridgeBio team for closing remarks.
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.