Oh, okay. Let's go ahead and get started. Welcome everyone, to the 42nd annual J.P. Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at J.P. Morgan. I'm joined by my squad, Loryn Hall, Priyanka Grover, Malcolm Kuno. Our next presenting company is BridgeBio, and presenting on behalf of the company, we have CEO Neil Kumar. Neil?
Well, thanks so much, Anupam. Thanks to the squad and the entire J.P. Morgan team, including Phil Ross, for having us here again. You know, we've been privileged to present here 7 of the 8 years we've been around as a company, and we've been through some ups and downs with all of you in this room. And I finally feel like we've arrived at the beginning, really a starting line, if you will. And what I wanna talk about for the next 25 minutes or so is how we intend to come out of that starting block to develop and to create a fully integrated pharmaceutical company that can serve patients with genetic disease at scale.
Before I get into specifically what that looks like in 2024, I wanted to provide you with some glimpses of what the finish line looks like from this race that's well worth running. I wanted to do it for two reasons. The first is just to remind ourselves what the power of best or first-in-class medicines can look like. The second is because many of you in this room have helped and supported us through the years, but unlike those of us that are operating, you don't get the frontline stories from the patients that ultimately your support is helping.
So I wanted to tell you a little bit about this young boy with molybdenum cofactor deficiency type A, where the natural history of the disease suggests he would no longer be with us, but where we received a Christmas card from him just recently, where he's celebrating holidays with his family. I wanted to tell you a little bit about a young girl suffering with Canavan disease, who, absent the therapy that your support helped create, would not be ambulatory, nor would she be able to hold her head up. And I wanted to tell you a little bit about a grandfather who's able to take his grandchildren to school today, where absent the therapies that you have helped to create, he would be dealing with late stage heart failure or much worse, deriving from ATTR cardiomyopathy.
This is the type of impact we can have with your support, and our hope and our aim is to build on top of these glimpses to ultimately create a reliable and sustainable platform to serve patients like these across the genetic disease landscape. So how are we gonna do that? You can see the cheesy depiction here of a starting line. It's really 3 simple things for 2024 on our side. The first is the effective launch of acoramidis into the ATTR cardiomyopathy space. The second is the continued prosecution of our late-stage development pipeline in key unmet need and large market areas like ADH1, achondroplasia, LGMD2I, and congenital adrenal hyperplasia. And the final piece of this is the ongoing research productivity of an engine that has provided us 17 INDs to date over the course of 8 years.
I don't have time in the 25 minutes that Anup gave me to talk about all three of these legs, but I will address the acoramidis launch and the late-stage pipeline, and I'm happy to get into the entirety of the pipeline during Q&A. Before I do that, I just want to remind everyone that BridgeBio is a company that exclusively plays in the area of genetic and genomic disease. By that, we mean both Mendelian diseases and somatic cancers with clear genetic drivers. What's true at the advent of the company and what's true today, is we are truly still at day one in this space. At day one, in terms of the unmet need for patients, some 8,000+ diseases, a vast majority of which don't have a single pharmaceutical therapy.
We're at day one in terms of the innovation that's being provided to us, mostly from academia, where we see increasing amounts of genetic information, an increased ability to tie that genetic information to pathogenicity and ultimately to phenotype, and a better and better ability to more precisely target these well-described diseases at their source. Within this exciting ecosystem, we have built an R&D engine that's fit for purpose. It allows us to efficiently discover molecules in the small molecule land, going in under $10 million in under 3 years from idea to IND. It allows us, with the capability we've built over 8 years, to efficiently develop those ideas in the clinic with some 20+ clinical trials, 500+ sites.
We know the right CROs, the right sites, and the right partners to work with to take an idea and ultimately translate it into something important for patients. And we house all of these activities in a decentralized architecture that allows for focus at the level of each disease or each biology, allows us to elevate the probability of technical success through that focus and to cut down things that are not working. All right, so what does all of this look like in 2024? I'll begin with the most important activity we have ongoing, which is the launch of acoramidis into the ATTR cardiomyopathy marketplace. And maybe where I'll start the story is just by reminding everyone what things looked like one year ago. One year ago, we didn't have any of the information that I'm providing on this slide.
First, and most importantly for our company, was the provision of data in the middle of this year associated with acoramidis in our phase 3 ATTRIBUTE trial, suggesting that ever greater degrees of stabilization, ever better decreases in the amount of toxic monomer that's depositing in the heart, can lead to unprecedented levels of survival and hospitalization. And as I'll comment on in a minute, the way we do that is we actually improve patients at a higher fraction than what has been seen before, and we impact the disease earlier than what's been seen before, as one looks at the composite endpoint of ACM and CVH. There were a great many other learnings in the space attributed to ATTRIBUTE, our phase 3 trial and other studies. First, and most interestingly, clinical care came to the forefront.
We found that standard of care itself greatly elevated levels of survival and decreased levels of hospitalization. It's worth noting that our placebo arm outperformed the on-drug arm of the ATTRACT Pfizer trial. As you saw at HFSA, as published by Dr. Masri, just a couple of months ago, although tafamidis still 30-month survival rate in real-world evidence studies is still around 70% survival, my estimate is that novel, more potent therapies like ours will continue to provide 80%+ survival in this area. Secondly, we're continuing to find patients, and we're continuing to find them earlier.
There's a great many ways one can measure this, but maybe the easiest way to do it is to look at the quarter-on-quarter growth of the tafamidis franchise, which is 15% as of last quarter, and the CAGR has been quite attractive over the course of the last couple of years. And then finally, and interestingly, we're doing a better job of marrying the right therapy with the right patient, and we're having an increased and more detailed dialogue around what response and non-response looks like. One can just go back to the AdCom around the APOLLO-B trial to understand how physicians are now using NT-proBNP, and maybe in the future, serum TTR, to try to understand which patients are responding to current therapy and which patients may need to move on to a new, more potent therapy so that they can better control ATTR cardiomyopathy.
Okay, so within this exciting and dynamic landscape, what is our value proposition? Again, shown by this interesting Parthenon slide. But in the roof, you can see the fundamental design criteria that we started this whole program with and that I've talked about with all of you, I think, in this room many times, which is that ever better levels of stabilization should lead to ever-decreasing amounts of toxic monomer depositing the heart, which in turn should lead to better functional outcomes for patients. What is the manifestation of that design criteria? It's really three things. One, unprecedented survival and hospitalization levels. Two, evidence of actual improvement for the patients that we're serving. And three, impact on the disease earlier than what we've seen before. And here you can see, in very small slides, effectively all of the data that we presented over the last six months.
Number 1, survival and hospitalization levels that look a lot like, for our population, what life looks like absent ATTR cardiomyopathy. Number 2, improvement levels of 40%-45% against key continuous variables like NT-proBNP, six-minute walk distance, and improvement levels in New York Heart Association class that haven't been witnessed before. And number 3, at the 3-month marker, actual separation from placebo against the composite endpoint of ACM and CVH. Today, I want to build on some of these exciting observations with two new pieces of data that ultimately will be published on at ACC and that we'll continue to elaborate on. I'll do so for a couple of reasons. One is because I think it's an exciting part of the differentiation story.
And two, it gives you some idea as to what we expect to do over the course of the next 12 months, which is to continue to interrogate the ATTRIBUTE trial database to provide patients and physicians with more and more information about how to use our drug usefully. So I'm going to start with survival, and actually, I see some of you in the room who are involved in this story all the way going back to Eidos BridgeBio days. And we had a lot of conversations back then about, well, how are we actually going to measure stabilization in the body? And does that increased level of stabilization associated with acoramidis actually lead to functional benefit in patients? And what does that response curve look like? Well, the best way we could think about measuring stabilization in the body were serum TTR levels.
Yeah, they were variable, but that was the best we could do. And the question that people were asking, even back then, was, ever greater degrees of stabilization, ever greater degrees of serum TTR, what does that lead to in survival? Many of you are familiar with the Hansen paper and some of the early Buxbaum papers in this space that looked at that question within the context of V122I patients or rare variant patients. Today, we can look at that question in the context of the wild type population, the larger population, and we can ask and answer the following question: Do elevated levels of serum TTR ultimately decrease probability of mortality? And what you can see here for the first time on the Y-axis is all-cause mortality probability, and on the X-axis is change in serum TTR associated with acoramidis.
And you can see in a highly statistically significant way that serum TTR is an independent predictor of survival probability. Okay, next question is: Who's doing better on serum TTR levels? Obviously, within the context of the ATTRIBUTE trial, we were able to ask and answer the following question in terms of a post-hoc exploratory analysis. Because recall, people dropped in on tafamidis after 12 months. Actually, double the numbers in terms of frequency of people dropped in on our placebo arm than did our active arm. And so we have a lot of patients that are on tafamidis, and we have patients that are on acoramidis. And as we showed at ESC this year, we have a 42% increased level of serum TTR in the context of acoramidis patients as compared to tafamidis patients when one looks at the populations during the 30-month ongoing trial.
But a question that we can ask and answer now, given our open label extension study, is: What happens when we take those very patients that are on tafamidis and put them on acoramidis? Can those patients actually go from the lower levels of serum TTR, the lower levels of stabilization, to now higher levels of stabilization, akin to what acoramidis patients have been experiencing throughout the course of the trial? And here, and I think very excitingly, you can see within six months, patients that were on tafamidis, that they're then transitioned to acoramidis, see an elevation of their serum TTR levels, akin to what those patients that were on acoramidis for the entirety of the trial looked like.... So exciting data here in terms of the tie between stabilization, serum TTR, serum TTR, and survival, and we'll publish more on that.
I wanna move to the second pillar now, which is that pillar of improvement. And, people tell me a picture is better than a thousand words, so I'll try not to use a thousand words to describe this. But, one of the questions that we've been wondering about is: What's going on in the heart? Actually, I was just talking to Rob Blum about this. When we started MyoKardia a long time ago, we also asked, "Well, in the pathomechanism of disease, might this medicine just halt disease but not actually reverse the disease itself?" And same thing in the course, in the context of ATTR cardiomyopathy, we thought we could turn off the deposition of toxic monomer, but the thought that we could actually improve patients was one that we always wondered about.
Now, obviously, at a functional level, we're seeing improvement. The question is: What's going on in the heart? And alongside Dr. Fontana at the NAC, who's one of the great researchers that we've been privileged to partner with, we can ask and answer this question using CMR imaging. CMR imaging is something that looks like the extracellular volume of the heart, which is effectively looking at the amount of amyloidotic plaque that's deposited into extracellular milieu around the cardiomyocytes. And what you can see here in the first row is something that's consistent with our understanding of the disease. What happens over time is that the amyloidotic plaque builds up, and you can see that with the ECV numbers going from 68%-78%. I won't walk through the details of the image here.
But very interestingly, in some of the acoramidis patients that actually experienced improvement, what we can see is an actual decrease in ECV over time. What does that mean? Well, it means what the slide suggests, that we're actually seeing markers of disease regression for the first time that I know of in this space with a highly potent small molecule. So that is extremely exciting data. The question now becomes: How are we gonna take all of this data and the rest of the data that we publish on this year and actually educate physicians and patients so that they have the appropriate options when they're diagnosed with ATTR cardiomyopathy? Well, there are 36,000 cardiovascular practices in the U.S. alone. That sounds like a pretty big footprint for a small company like ours to get across.
But the good news, in this space, is that we know precisely who's prescribing, we know where they're prescribing, and it turns out to be a relatively constrained environment within which we feel like we can commercialize effectively. So it's mostly cardiologists, as you see on the left-hand side of this slide. It's mostly constrained to geographic regions that we know pretty well, although our hope is that it will grow. And the growth is today occurring from the 100 or so centers of excellence, going to about 1,100 or so heart failure specialty clinics that are really diagnosing and seeing these ATTR cardiomyopathy patients. That feels like a much more doable problem for a company like ours to solve.
It's increasingly solvable when one considers the fact that we have a team that has a lot of CV experience, that has deep relationships with these centers of excellence, and ultimately has deep experience in the context of marketing drugs in the Medicare Part D side of the formulary, which is an important piece of ultimately the commercial dynamics here. So what at a high level is our go-to-market strategy? It begins by establishing acoramidis as the backbone of therapy within this space. Again, going back to the design criteria, we always thought that the agent that most effectively reduces the amount of toxic monomer and keeps TTR around should be the starting place for most patients. And that is our goal here, to establish acoramidis as the start place for physicians and patients alike.
The second key piece of our go-to-market strategy is a focus on access and affordability. When one looks at the patient journey, one sees that physicians' prescription initially of this high-cost drug, coupled with patients' ability to comply with the drug, given current financial toxicity, is a key pain point, and so we will be focused there to try to alleviate as much of that pain as possible. We couple that with continued evidence generation, both, as you can see from publishing on what we've learned from ATTRIBUTE, but also from running novel trials, like our ACT-EARLY trial, to try to understand where else these medicines might be useful, how early these medicines might be useful, and how else we might diagnose these patients ever earlier. And then finally, this is all we're doing. This is all our commercial sales force will be doing.
This is all our MSLs are doing. This is all our FRMs are doing. We believe that focus elevates the product, and ultimately, our hope here in focusing uniquely on ATTR cardiomyopathy, is that that focus will derive into a better product for the patients and the physicians that we serve. All right, so a lot of investors have been asking me: "How are you gonna size these efforts? How are you gonna size the field for us? You know, what, what ultimately do you think you're gonna do in terms of share of market?" And obviously, it's impossible to tell right now. We haven't commercialized anything. We're not approved yet, so it would be inappropriate to do so.
But one thing we can do is we can do some market research, and I think we've shared the results of one of our market research surveys that was pre-Part B, but we've been able to conduct a couple more studies post the Part B readout to try to understand where we're gonna sit, absent even any commercial push right now. Pretty reliably, we're coming down to these numbers of between 25% and 40%. I think that there's a couple interesting things to remark on this slide. The first is that this share contemplates a four-player market... two knockdowns, two stabilizers.
We do account for the fact that because the knockdowns have a longer duration of their trials, and they are in healthier populations, that we expect their relative risk reduction will be slightly better than what the stabilizers were able to do in sicker populations at shorter duration. The second thing, in none of these surveys, did we include any real safety data. Obviously, we're very pleased with our safety profile, but there are small things on the margin that can move things around. Obviously, we're preserving TTR while the knockdowns do not, and we don't have the counterindication that tafamidis has around Crestor, where tafamidis cannot be used alongside Crestor, whereas we can. There are small things that were not included in here that could shift these numbers ever so slightly, but these are the numbers that routinely we're getting from our survey methodology.
An interesting thing that we've found as we go out and we survey the field is that cardiologists are very, very knowledgeable about how to put together PK/PD and how to compare various small molecules, and how to look at small molecules versus other modalities. Here you can see on this slide, the fact that small molecules have really dominated most of the cardiovascular therapeutic spaces for a long period of time. We're very privileged to be learning from the cardiologists out there about what evidence we need to generate to continue to differentiate our small molecule versus many of the other therapies out there. Okay, so again, what does all this look like for 2024? We've submitted our NDA. We're gonna submit to the EMA very shortly here.
We're gonna continue our lifecycle management, including the kickoff of our primary prevention study, coupled with some exciting new progress in our QD formulation, which is coming along quite nicely. You're gonna see additional data from us at every major conference this year, and ultimately, this all builds to our anticipated FDA approval and the commercial launch of our product at the end of the year. All right, with the remaining time, I'm gonna turn to the rest of the late-stage pipeline. I'm gonna do about a slide each on these programs, and then I'm happy to dive into any details with the remaining time. And I'm gonna start with our program in achondroplasia. As many of you know, this is a condition, the most common form of dwarfism, that uniformly arises from gain-of-function mutations in FGFR3.
The design criteria here was to create a best-in-class compound. Best in class in which ways? Number one, efficacy. By targeting this well-described disease at its source, our hope was that we would be able to gain incremental efficacy as compared to the other agents in this space that only target one of the two effector pathways. Secondly, we wanted to be able to do so with better convenience. Ours is a once daily oral. Actually, it's a once daily sachet, so you can mix it into your cereal if you want for your child, as compared to the once daily injection of our competitor. And finally, we wanted to be able to get to that efficacy safely, avoiding injection site reactions and the hypotension associated with some of the CNP therapeutics.
On the right-hand side of the slide, you can see some of the phase 2 data that we presented this last year showing incremental efficacy versus anything that we'd seen in the field before. Importantly, across all key measures, including change from baseline and average height of growth velocity, including the responder rate and including the actual median AHV that we saw over time. By the way, our hope here is that this is the tip of the iceberg for efficacy. Ultimately, the community here cares about things like proportionality, impacts on spinal stenosis, and we are the only agent we know of that's been able to show in preclinical studies, impact on that broad and diverse set of symptomatology. So we'll be looking for that in our ongoing phase 2 studies, as well as in the phase 3 study that we have kicked off.
In terms of next steps here, we expect complete enrollment of a trial that has been enrolling at a very fast clip. There's a lot of demand, as you can imagine, for this medicine right now. We expect the initiation of a related trial in hypochondroplasia by the end of the year, and we will publish our long-term follow-up data in collaboration with some of the seminal PIs in a high-impact journal this year as well. So that's what to expect from achondroplasia. The next program I wanted to mention is our program in limb-girdle muscular dystrophy type 2I, a condition that affects about 7,000-10,000 people between the US and the EU, that uniformly arises from loss-of-function mutations in an enzyme called FKRP. Here, we transition from potentially best-in-class therapies to first-in-class therapies. There is no available pharmaceutical therapy for this disease today.
What you can see on the right-hand side of this slide are the phase 2 data we presented again last year, suggesting that our approach, which is a substrate replacement approach that effectively replaces what is missing from FKRP, which is the glycosylation of a complex called the alpha-dystroglycan complex, that we were able to rapidly increase the amount of alpha-dystroglycan glycosylation within the context of patients. And that importantly, early rises in alpha-dystroglycan glycosylation ultimately led to functional improvements in 10-meter walk time and the modified North Star test, something that's inconsistent with what we've seen in natural history.
We used that bevy of data to approach the FDA to talk to them about how we might design a phase 3 clinical trial with an interim readout that just looks at the statistical significance of increasing alpha-dystroglycan glycosylation, with key secondary endpoints, including ambulatory measures as well as FVC. And I should mention, as many of you in the room know, there is literature just this last year suggesting that increased elevation of FKRP itself leads to improvements in FVC within this clinical community. We were not able to measure FVC in our phase 2, given the fact that we ran through COVID. So very exciting ongoing trial. Again, we expect complete enrollment of this trial this year and the interim readout for accelerated approval sometime next year. I'll turn then finally to maybe our highest probability of technical success program, which is our program in ADH1.
ADH1 is a disease of calcium dysregulation that arises uniformly from gain-of-function mutations in the calcium sensing receptor. Our approach here is simple, as all of our approaches are simple, to target the well-described disease at its source, to allosterically inhibit the gain of function CaSR, so that we might increase serum calcium levels and decrease urine calcium levels, to normalize them. And what you can see on the right-hand side of this slide here is data from our phase 2. Now using the interpretation of what full response looks like, the interpretation that we are using as our clinical endpoint in our phase 3. So full normalization of urine and serum calcium levels. And what you can see is on drug, we had close to 70% responder rates, whereas off-drug, close to 0% responder rates because standard of care is vitamin D plus calcium.
So as you can imagine, it's not, it's not very effective. So a very, very high probability of technical success here. The trial is incredibly well powered. I will say the trial has been slower to enroll than we anticipated, mostly because it took us some real time to activate three of the key clinical sites, two of which were government sites. They are now activated and is enrolling at a reasonable clip. So our expectation here is that, again, the trial fully enrolls this year and that we'll have data early next year on this drug as well. All right. So, Anup, I know I'm getting into the Q&A time, but I want... I didn't, I didn't wanna leave before talking a little bit about CAH because you've been riding on it.
A lot of people haven't been thinking about this one that carefully, but this is a shared piece of interest for us. The disease is congenital adrenal hyperplasia, which is one of the larger unmet needs within the context of Mendelian disease, affecting some 75,000 people worldwide, and it's newborn screened for actually in the U.S. and the E.U. Again, this is uniformly arising from loss of 21-hydroxylase, which is a key enzyme involved in cortisol production and the regulation of the pathway you see here on the right-hand side of this slide. Now we shift to a best-in-class hypothesis. The therapies that are available to us out there today, exciting therapies called CRF1 antagonist, deal with the top end of the pathomechanism of this disease.
So effectively, what happens when you have this disease, you can't make cortisol, you take endogenous steroid. There's too much flux across the androgen production pathway, and CRF1 antagonist can help with things like 17-OHP regulation and A4 regulation. The goal of our approach, which is a gene therapy that replaces what's missing, again, targeting a well-described disease at its source, is not only to provide the type of efficacy on A4 and 17-OHP that CRF1s have already, and we've already actually accomplished that, even at low dose. But more importantly, to, for the first time, provide endogenous cortisol production for patients that are lacking it. And here you can see some early data from the first three doses that we have interrogated in the clinic, and I, I would... I'll qualify these data as exciting but not there yet.
So based on non-human primate work, we thought these first three doses would be adequate to get us to levels of cortisol production, 10 micrograms per deciliter or potentially even more, to fully steroid spare the patients that we're attempting to serve. What we found was that across the first two doses, there was limited response. But on the third dose, which is 6 × 10^13, you're seeing a very, very nice increase in the precursor to cortisol, 11-deoxycortisol, as well as cortisol itself. You never see 8+ micrograms per deciliter levels in a CAH patient absent some sort of therapy. So the transgene is clearly active. We're excited about this data, but we don't think this is as good as we can do. So in collaboration with the agency, we are actually interrogating another now twofold higher dose, 1.2 × 10^14.
We've already dosed a patient at that dose, and the second patient is coming in for dosing late this month. We will have that data in late August, and we consider this data a go, no-go for this important program. If indeed we can get to high levels of cortisol production, 10 microgram per deciliter or more, we believe this is a unique and valuable therapy for those patients. If it's just a convenience play with a gene therapy that effectively is one and done, but is only doing what the CRF antagonists do, that's not for BridgeBio to prosecute. That might be relevant for another company to prosecute. So that data will be coming in August. All right, so I talked about a lot of programs. Let me just reiterate what 2024 looks like at a high level.
Launching acoramidis is the first and most important goal that we have for the year. Second is the full enrollment of our ongoing phase 3 clinical trials in billion-plus-dollar markets and large unmet need markets, and the readout of our phase 2 in congenital adrenal hyperplasia. And then finally, is the continued establishment of our strong financial position, where today we have about $560 million on the balance sheet, and you can expect some imminent activity in and around that as we further buttress our balance sheet so that we can take on all this activity that's important for patients throughout the course of the year. So with that, I'll stop and take any questions.
Thanks, Neil. I just wanna remind folks that there's three ways to ask a question. Old school, raise your hand, I'll call on you. There's a portal here where you can ask questions, and... or you can just email me. But I'll just start. You talked about the launch of acoramidis in the back half of the year. What are the key sort of market education efforts planned for the year as you go into launch?
Market what?
Market education efforts.
Market education efforts. I mean, I think, you know, first and foremost, what we can do is we can publish strong data associated with the ATTRIBUTE trial, and that's gonna be the cornerstone of market education that we can do prior to approval. Obviously, we can be out there talking to payers as well, and we have a force that's already doing that and talking about a differentiation story. You know, absent that, we're gonna have to wait for FDA approval to really get out there and do what we can do in terms of the drug itself. In terms of disease state awareness and education, we're actually doing quite a bit. Obviously, the number of people that are on drug today within the ATTR-CM community is probably less than 20,000.
You know, even the most conservative epi estimates would have it at 250,000-300,000 people, 10%-13% of HFpEF patients likely have ATTR cardiomyopathy. So we and other sponsors have a lot of work to do to get the word out on look for ATTR, especially in those non-centers of excellence, those heart failure clinics, where they're seeing a lot of HFpEF.
Questions from the audience? Go ahead.
... like biomarkers to see the efficacy. Do they help as well in the diagnosis? I know that there is improvement in the diagnosis because the main challenge was the diagnosis of the disease. And I can see from your side that there are a few, you know, few markers to diagnose. Is it established or it's just in the discovery phase, just because usually they used to wait until they have an event and then they look into it?
Yeah, that's a great question. So in terms of a disease diagnosis, the mainstay is still technetium scans and imaging. It's more the biomarkers that we're talking about here mostly relate to the progression of disease once you have been diagnosed. So the NAC staging criteria, some of the univariate predictors of downstream mortality and morbidity, those are generally being used in the context of an already established ATTR cardiomyopathy diagnosis. But it's a very, very intriguing area for research, both actually from the AI standpoint around imaging, as well as from the standpoint of just using a classic serum TTR or NT-proBNP as at least a canary in the coal mine, so that one might look for and do a technetium scan coupled with a, you know, making sure it's not AL. Yeah.
We have a couple questions in the portal. So on the acoramidis filing, did you ask for priority review? Are you expecting a priority review, and what are your expectations for an adcom?
So on priority review, obviously, tafamidis is already out there, so I would, I would suggest that that is an extremely low probability that we get a priority review. I do think we'll have an expeditious review, and I would think it's a very, very low probability that we have an Ad Com.
With the HELIOS-B results coming this year, how do your commercialization plans change depending on what HELIOS-B shows?
Yeah, that's a great question. I mean, I think that's a little bit why we showed that market share research, which is, I do believe the small molecules will continue to be the backbone of therapy for a great number of the prescribers in this space. Obviously, with HELIOS-B, you have a trial that's gonna be hard to compare to the trials of that that we're attributing to TRK because it's longer duration and it's a healthier population. And so the, you know, cross-trial comparisons are gonna be quite difficult. But I think, yeah, you know, we're gonna stick to our guns here. We think we have by far and away, the best reducer of toxic monomer coupled with keeping TTR around. That's a good place to start for patients.
Questions from the audience? Maybe just switching gears quickly to infigratinib. You talked about enrollment being completed here in the first half, right? And data next year. Can you talk about the enrollment curve and dynamics there? Because that's a lot faster than, say, I think even BioMarin was able to do, which took, like, 18 or 24 months. So what... You just had a run-in period start, like, last year.
Right. Yeah, no, that's a credit to the team, and a little bit goes back to the flywheel. We're getting better and better at late-stage clinical development. But I would also credit BioMarin in getting the awareness out there. Obviously, their drug is not available worldwide right now, so we've been able to pick up on some of the latent expectation in and around getting patients getting kiddos on therapy, number one. Number two, you'd be surprised at how many people actually just do not want a daily injection. Needle phobia is actually quite a bit larger in terms of a percentile of children than it is of adults. So, there's a huge latent population there that we've been able to tap into.
And then thirdly, just the exciting efficacy data that we were able to put out there. This is broadly disseminated within the community and has helped to drive a lot of excitement. The numbers of patients here are quite high. The numbers of kiddos here are quite high, so.
Questions from the audience? On encaleret, you mentioned the delay in enrollment. I think you mentioned it to a few specific sites, but maybe you could talk about the size and scope of the geographic breakdown, where these sites are, and if you're comfortable now with everything, given the delay.
Yeah, I mean, the big part of this is obviously we're very closely partnered with the NIH and the turnaround of IRBs and things of that nature in some of these seminal sites is hard to predict, and maybe we were too aggressive in our understanding of how the trial might kick off. So I do feel comfortable now with how the trial is pacing. I would say what's interesting when you go into the... And we're actually gonna publish on this later this year, but when you go into the UK Biobank or any of the databases that we have access to, and you look for gain-of-function mutations in the CaSR that are pathogenic, you get, like, 10,000-12,000 patients in the US that actually have ADH1. So that's a large population.
And if you look at some of the diagnostic work we've done within the subpopulation of hypoparathyroidism, you also get to similar numbers of, like, you know, 6-7 thousand patients. So the trial should be enrolling quicker if those are the true numbers of patients that we see out there. It's enrolling more like a 3-4 thousand patient population trial right now, and I think the reason for that is the diagnosis is quite low, and it's a pretty spread disease. There aren't like, absent the NIH, there aren't like huge populations of patients that we can immediately dip into. So that's gonna be a bit the commercial work, honestly, is to diagnose these patients more readily and, you know, to understand what kind of footprint we need to get after it.
Maybe final question from me. Neil, you talked about your cash position and making some, some amount of, I think you called it progress around that. So is that refinancing the debt? Is that getting, bringing in non-dilutive capital? What, what, what is that?
Yeah, I mean, I think, you know, people make fun of these broad statements that I make, but we're always seeking the lowest cost of capital, right? I mean, management is big owners of this company, and we care about stuff like that. So yes, to all of those things. I think we'll be looking to do what we can on finding great partners on the debt side, as well as "non-dilutive" aspects like royalty financings and strategic partnerships that allow us to serve patients as broadly as possible with some great new partners. And I think you can expect that we're gonna put some runs on the board in this quarter here.
Okay. Any final questions? All right. Thanks, everyone. Thanks, Neil.
Thanks, guys.