BridgeBio Pharma, Inc. — Call Transcript 2026

All right, cool. Good afternoon, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thanks once again for joining us at TD Cowen's 46th Annual Healthcare Conference. For our next session, it's a privilege to have a fireside chat with BridgeBio, it's a pleasure to introduce Neil Kumar, the CEO of BridgeBio. Neil, thanks so much for joining me. Thanks. So, um- Appreciate being here. What's that? Appreciate being here. You got it. Look, Neil, the stock has corrected a little bit as of late after the huge run it had in the year prior. Personally believe it's a bit of kinda sell the news post ACON. Maybe some are just shorting it in the kinda near-term window ahead of the TAF IP trial and a lack of clinical data readouts. I don't think anything about the fundamentals of the story has really changed. They've continued to improve, obviously, with the 3 Phase 3 readouts. With that said, curious to get your perspective on that and your thoughts on the TAF IP situation as well, given that the trial's coming up here shortly. Yeah, sure. Thanks for the question. Obviously, we've noted the pullback and the disconnect between intrinsic value and where the stock's trading now. I'd say first, we feel very privileged to be sitting on top of the last three phase threes, certainly in ADH1, LGMD2I, and the latest in achondroplasia. They all met or beat our expectations in terms of service to the patient communities, and we can go through the details of any of those, and I think that liberated a reasonable amount of intrinsic value, certainly in our models. What's weighing on the stock, I think people in this room probably have a better idea than I do, but in large part what we've been hearing is it has to do with the TAF IP overhang. I'm not gonna make a huge deal out of it here. We tend not to talk publicly about our competitor's IP situation, but I obviously will say that the trial is upcoming in late April, and we believe Pfizer has very, very strong arguments both from the standpoint of infringement and from the standpoint of validity. Obviously Form I, lowest free energy form polymorph, we think it's well protected, and we think that it shows up in all the generic batches and otherwise Pfizer would not be basically asserting the claim against every single one of the generic manufacturers in our view. Again, I think they also have a very, very strong set of orthogonal methodologies that allow them to pick up Form I, obviously solid-state NMR, X-ray diffraction, as well as Raman spectroscopy. We feel good about that. Then on the validity standpoint, from the validity standpoint, which obviously has been a little bit more controversial given what happened in Europe, we really have to remember that in America, the bar is extraordinarily high for validity. If you're gonna make Form I, you gotta make it every single time that way, and then it's inherently anticipated. If even one or two times out of 100 you get something else, then it's not inherently anticipated. Because Pfizer did not document the acidification step in the context of Vyndamax, we believe, and you can see this from the fact that generics have been able to patent metastable or amorphous forms of the crystal, that you're not always gonna get Form I, and therefore we believe the patent is both non-infringible but also a valid patent. Again, that's our view. We'll leave it to Pfizer and others to sort that out. Our view is also that ATTR is a clinically differentiated molecule and in any circumstance we'll be able to continue to grow the brand for many years to come. Okay, great. Thanks for that. Trial starts in April, and presumably they need to come to some sort of ruling or decision by the November timeframe? Exactly, yeah. We expect to hear anywhere from late summer to November. Okay. I think honestly, in the first couple days of the trial, we'll have a sense as to whether or not they can assert those claims and really drive toward infringement for all the generic manufacturers. I think we'll have a sense here, end of April, be my guess. Regardless, there's gonna be an appeals process that plays out too, right? It'll be accelerated? Not in the U.S., no. Okay. Different. I mean, in Europe, what you have is you had the ruling, which obviously went in their favor, you had the appeals process with a couple scientists who took issue with the validity aspect with a different bar, probably a little different than the judge. Recall that they withdrew the patents at that point, there's no legal precedent that floats over to the U.S., but this will be the ruling of import. There will be no appeals process after that. Okay. All right. Pediatric exclusivity end of 2028, so earliest basically the generics are launching in 2029. If they do a 180-day exclusivity with single filer, could be, multiple generics later in 2029. Settlement would be like a 2032-2033 timeframe. The third scenario is the TAF IP holds up, and then that's 2035. That's right. Okay. By the way, we think that third scenario is highly probable based on what I just discussed. I know IPD and others believe the settlement in 32 to 33 is the most probable scenario, but we disagree. We're obviously not IP lawyers over here, so we'll just have to see how it plays out. I think it's important to note even past clinical differentiation that this is a Medi-D focused orphan drug space, and so obviously if you sort of break down the economics in the channel, patient co-pays are gonna stay the same whether you're on a generic or whether you're on a branded drug. Obviously all the distribution networks are gonna actually want branded, especially the ISPs. I mean, we see this a lot in the context of academic medical centers. Ultimately, I think physicians are gonna wanna work with a branded distributor who is focused on doing hefty research like we are. I mean, I don't think anyone's running a primary prevention study like we are, a $400 million Act Early study. We've been doing a lot in real-world evidence. We've been doing a lot in subpopulations like the variant population, AFib population, and the like. I think we'll continue to try to differentiate the product and learn more about how small molecule stabilizers can be used to the benefit of patients overall, both earlier and in more severe settings. Great. Now kind of staying at a high level, we have the ongoing Atrubie launch as well as the 3 NDA filings from the 3 positive phase 3s that just read out over the next year or two. Can you talk about your plan to manage expenses and cash runway all while continuing the Atrubie launch and these 3 new product launches? Yeah. I mean, I think, it's no surprise that every single one of these upcoming launches is gonna be materially cheaper than the Atrubie launch. Obviously, the field force for TTR is larger, plus we have an already established commercial infrastructure now. A lot of what you need to do for distribution design, patient services, certainly market access, incentives, sales force training, all of that stuff is already set up. Yeah, there will be an incremental tick-up in commercial spend. I think R&D will be flat to declining obviously as we bring some of these large phase threes off, and so we feel like we're very well-financed given the well over $1 billion that we have on the balance sheet, to get to profitability should we choose to do that. What sort of headcount and field footprint do you think these next three launches need? Maybe could put that into perspective relative to the Atrubie effort. Yeah, hard to tell. We've never really disclosed precisely the number of reps we have, I think, on TTR, but it's no surprise that one of our competitors has disclosed around 140. We're not that far off. That's probably a multiplier of 4 more than you need for something like a rare disease like LGMD2I or ADH1. Those will be small field forces. In fact, in some cases, I think the MSLs might be half the headcount of the actual field force. Got it. What phase of preparations are you in for these 3 new launches? How ready are you guys to launch these products? All the commercial leaders have been hired. Medical affairs is out there for each, for each one of these pieces. Obviously, we, we're filing these NDAs, and we need to get approved before we can really turn on the gas. You're also able to send out your FRMs based on your phase 3 data and start to learn more about what pricing could look like. We're doing that as well. I would say everything we can do right now, appropriately, we are able to do. Very unlike actually in the context of an ATTR where we were so broke that when we hit, when we hit on that phase 3, we're like, "Oh, great." "Let's hire a commercial force. Moving to ATTR and acoramidis specifically, can you talk about the key factors driving the momentum today, the biggest contributors to the strength of the launch, and what gives you confidence that this is going to be a multi-year sustained growth of the franchise as opposed to just a strong first full year of launch? Yeah. It's, pretty multifactorial. The strength actually, to me is indicated by that second derivative that's now gone positive again. You don't tend to see that as much in rare disease launches, at least as we modeled in our revenue institute. You see this explosion and then you kinda like, constant growth. The fact that we are, we're growing growth, if you will, quarter on quarter, and we're having basically the best couple quarters that we've had to date suggests a couple of things. One, I think we're doing a better job collectively as all the sponsors in the field in identifying patients and driving the call point, even outside of academic medical centers to high volume heart failure practices. We obviously haven't diagnosed even maybe 1/4 of the number of ATTR cardiomyopathy patients that almost certainly exist in the United States. That's work that needs to be done. I think, I was probably skeptical on this at first, but a large part of that is these sorts of AI, what people call AI, but it can sometimes be, a few factor sort of red flags that say, "Hey, consider this FF patient. They may have ATTR cardiomyopathy," and then that drives people to think of it and go to technetium scan. That's number one. Number 2, I would say is the generation of additional clinical data, both in the context of the early separation, which I think is really starting to catch on and you should stay tuned for more research on why that is occurring, I think uniquely for our compound. But I think secondly and key in certain subpopulations, like the variant population where we had a 0.41 hazard ratio with stat sig, which is the best point estimate and statistical significance in the space. But also importantly, the AFib data. Recall, like almost I think 60% of patients or so on this channel have some cardiac arrhythmic involvement, and what people often will look at is the relative risk reduction or the 17% reduction. Really what I think is most important is Atrubie works both in the context of AFib and in the context of non-AFib. If you're a prescriber in the field, especially outside of an academic medical center, you can prescribe Atrubie to all the patients that may have ATTR cardiomyopathy, and I think that significantly simplifies the script. Great. Is it fair to say you expect significant quarter-over-quarter growth each quarter this year? How do you think about the overall market opportunity? Do you think it has a real chance of becoming a $20 billion market? Yeah, I do. I think, from a top-down perspective, there's still no study that suggests anything south of 12% of FF patients having ATTR cardiomyopathy. From that standpoint and the pricing stamp, coupled with where price is going, and where price is actually even today, I don't, I don't foresee there being an issue, getting to that size of market. I think from the bottom up, at least for us, we're seeing increasing education, we're seeing increasing prescription base in terms of number of prescribers. I think that that all portends continued growth. What are you seeing, from a competitive standpoint in the market from both, Pfizer's franchise as well as Alnylam? Obviously, a different approach, in terms of the impact that it's having on your launch. Are you guys really, it just really comes down to your own execution, and you're kind of unimpeded in your launch? I think a lot of this comes down to our own execution, to be honest. I feel like sometimes we're working all together as sponsors, to really grow the space. Each one of us have a different segment that I think we're strong in and, by and large, I would say, like, I mean, for instance, Pfizer just published two papers in JACC on the usefulness of serum TTR. That helps us because we obviously have a superior profile in terms of elevating serum TTR, but it reinforces to physicians the fact that for every mg per deciliter increase in serum TTR, you're getting about a 5% relative risk reduction in mortality at 30 months. Continuing to drive those types of stories into the marketplace, I think will be to the benefit of all medicines, but especially a superior stabilizer like ours. Bayer's getting a great early penetration in Europe with Beontra. Can you talk about the contribution of that ex US launch to the BridgeBio P&L and whether you expect that to start contributing this year or next year? Yeah. I think this year it should start to contribute in a meaningful way, obviously, given the high royalties that we're a beneficiary of. I think Bayer's done a absolutely marvelous job of launching in Europe. Obviously, totally different commercial dynamics over there, and they've been able to secure a majority share in Germany and a few other marketplaces where we're actually the only drug in the national bid. Well, we're excited to see how they continue to grow the brand over there and to continue to learn from them in terms of how best to position our product here. Great. We gotta move to the 3 phase 3s that I've read out and the 3 new product launches. We'll start with infigratinib achondroplasia. Your recent data exceeded expectations on both efficacy and safety, really stellar data. I guess following the data that you reported, what's your latest assumptions in terms of potential market share that you could achieve relative to the injectables? Yeah, I mean, we did a preference, share survey that I think I commented on in the last earnings call suggesting that we could get to 65%. I know the, most of the KOLs are saying something like 80%. I think just stepping back, I don't know what the right percentage is. We haven't done, the full degree of work yet, and we won't until we get the label. One of the things that's interesting is generally in a marketplace like this, it's probably 25% penetrated right now, and at least according to our market research, maybe 35% of patients in the United States are needle phobic, so they're not gonna be taking the existing products. Our hope is that like many orals from Fabry to migraine, we both enlarge the TAM as well as take significant share from the existing products. I think the share taking would be associated with greater efficacy, a better safety profile, and obviously a more convenient profile as well. It really does feel like, this is a medicine that the community is excited to welcome and I think we should be off to the races with this launch. How large do you think this market is and, how does hypochondroplasia add to that? What are your expectations for infigratinib and hypochondroplasia? Just as a reminder, hypochondroplasia is a similar hyperactivating mutation in FGFR3, the N540K mutation. It's a little less hyperactivating, and again, in animal models and cellular models, infigratinib targets this well-described condition at its source and is able to rectify not only the height symptomatology, but things beyond that. Our expectation is at this dose, which is a safe dose, obviously, we should be able to deliver best-in-class efficacy there as well, and we think that market is actually similarly sized to achondroplasia. Probably a little less well-defined, but similarly sized ultimately when you look at the statistical genetics. Got it. Is it $5 billion potentially with Acon and hypochondroplasia combined? Yeah. I think that's a rough sense. We haven't said anything about pricing yet, but, yeah, that would be roughly there. Okay. Maybe just you could talk about the status of the hypochondroplasia trial, when we'll get the next data readout. Again, what expectations should be and also phase 3 start. Yeah. It's hard to tell precisely what the bar is. Yes, we haven't seen the bar from any of our competitors really. I'd say right now it would be statistically significant impact on the condition. You'll see data later this year, ultimately phase 3 starting next year. Yeah. Okay. All right encaleret also exceeded expectations there. Maybe we could start again with. Actually encaleret and limb-girdle, let's discuss those kind of together. How do you think about the market sizes- The two forgotten products? Yeah, exactly. For both of those programs. You know, if you had to pick, one of your children, which one would you pick? Which one, which market opportunity or launch are you most excited about? I'm excited for both, to be honest. I mean, I think two very different profiles. On LGMD2I, the one thing I would point out is if folks call around to muscular dystrophy clinics right now, there's a reasonable number of patients that are already identified. You could see that through natural history. It's also congruent with how quickly the trial enrolled, given the prevalence. We think there's maybe 1,200-1,300 patients in the U.S. and a lot of them are already identified. I think that launch is gonna be premium priced and go fairly quickly if we can serve those patients, well, as quickly as possible, I think that's what we'd be intending to do. ADH1 a little different. Obviously, the statistical genetic prevalence is massive, 10,000-12,000 in the United States alone, that is not the number of identified patients. You know, we think that there's maybe 2,000-3,000 hyper symptomatic identified patients right now. We've rolled out a genetic testing program that I discussed at someone else's conference that we continue to build upon in the non-surgical hypoparathyroidism community to find more and more of those patients that are really hiding within that space with hyperactivating mutations, the CASR. I think that actually launch will be kind of a slower build, ultimately we'll get to similar peakier sales. Maybe you could just elaborate on that genetic testing program, how you expect it to progress, and how you expect to diagnose these additional patients? Yeah. About, 130 different hyperactivating mutations in the calcium-sensing receptor. We know what they are. We've characterized them. We published a paper on this last year that I think you and I discussed. We've got a panel, and what we can do is we can offer that panel at cost to a prescribing physician, potentially prescribing physicians in the future. Today, physicians that just wanna understand better what the genesis of calcium-induced regulation might be in, let's say, a hypoparathyroidism patient or someone who's you sort of classified as a hypoparathyroidism patient today. Is it fair to say that, both of these opportunities, ADH1 and Limb-girdle are billion-dollar-plus opportunities in your view? Yeah, I would think so. That's, I would say for LGMD2I, it's not obvious what the additional indications might be associated with BBP-418. There's Fukuyama syndrome, ISPD mutations, but there's not a whole lot else in that pathway. It's interesting to speculate as to whether or not hyperglycosylation of the complex might be relevant in the context of some other muscular dystrophies, but we haven't seen a genetic signal therein yet. I think that's one piece of it. On ADH1, obviously, we'll be kicking off a phase 3 in chronic hypoparathyroid, I think that is another very large opportunity for us. That could be $1 billion, could be well over $1 billion if we hit on that phase 3. Yep. Yeah, the Phase 3 RECLAIM-HP study in hypoparathyroidism. Maybe you could just reiterate both what you saw in Phase 2 and also mechanistically why you have such confidence in Encalaret in hypoparathyroidism. Yeah, it's a little different than our normal approach, right? Typically we start with pathomechanism, and we try to target the well-described condition at its source. Here, we were looking at the phenotype of the drug, if you will, and trying to match it up with an unmet need. In the context of chronic hypoparathyroidism, it's obviously a disease that's solely about calcium dysregulation, but it stems from a lack of PTH. Giving back PTH would make sense, and that's obviously what our competitors do. There are some issues with that long term in terms of bone abnormalities because you're not doing it in a physiologic way. When we look at our drug, what we realized was we were able to normalize urine and serum calcium through antagonism of the calcium-sensing receptor and to do it in a PTH-independent way through really the action of the kidney. That's what got us excited about exploring the agent in that space. We did a, I hesitate to call it a phase 2. It was really a signal-seeking 10-patient study, but what we saw was 80% normalization of urine and serum calcium in the context of chronic hypoparathyroidism patients. That's what gave us the confidence to really move it into phase 3 aggressively. It would be the only oral agent. I think it would be actually something that the community would welcome if we're able to deliver on the promise of the phase 2 or signal-seeking study. I guess just to follow up on that, you think mechanistically there's a chance that it could be superior to the PTH analogs in hypoparathyroidism? I mean, I think it would Mechanistically, it should be able to deliver better urine normalization, urine calcium normalization, and it should be safer. It's oral. At the very least, it should be competitive. Great. when the ADH1 data came out, some folks were like, "The PTH analogs can treat ADH1 patients." Curious to get your thoughts on that if currently ADH1 patients are being treated by Aurba or Natpara? No. Almost none of them are to be honest. There was that very small study that was published in The New England Journal, suggesting, inferior levels, obviously of urine calcium normalization. I don't think it'll be competitive in the context of ADH1. Great. Okay. All right. Just, on going back to limb-girdle, can you elaborate on those conversations with the FDA where they supported a traditional full approval with the NDA, and how those conversations went? I mean, I would say that, generally, this division is not seeing a whole lot of datasets that were as uniformly consistent. When I say uniform consistency, I would talk about 2 real measures of it. Number 1 is across different functional outcomes and inclusive of modified North Star, which I think was quite surprising, even to us and heartening. Then the second is across subpopulations. heterozygous, compound heterozygotes and L276I, old and young, ambulatory, non-ambulatory. I think all of those things together, it really the agency is looking for that level of consistency to make sure it's not outliers driven. It's, a true statistically significant impact, and that's, I think, what all led to, the enthusiasm around submitting for full approval. I guess just to round it out for both of these, indications and potential launches, ADH1 and Limb-girdle, based upon your filing timelines, you guys could be launching both of these drugs in the first half of next year. Yeah, that's right. Okay. infigratinib for achondroplasia obviously would be after that next year. Yeah. I think the first half of next year is doable as well, but let's see. Okay. How do you think about, again, balancing executing on these launches and building out the pipeline? What might we see from the internal pipeline over the next year or two, as well as, potential external opportunities? Yeah. I mean, I when I talk about the external pipeline, I include our sister companies and probably most relevantly, Gondobio. Within that, I think we have a vast array of technologies that we're working with. Obviously, we've talked about what we think is a best-in-class EPP program. We have two other clinical programs, one in CMT1A, one in alpha-1 antitrypsin. We have some seven development candidates that we think we'll hit on varying from TSC and rev inhibition to a novel mechanism in the context of ADPKD. There's a lot to be done, and I think we've already proven that we have a very efficient late-stage development, and hopefully, we will prove that we have a very efficient commercial engine that can be deployed at scale at BridgeBio. Bringing all these things together makes a ton of sense. Timing of that is TBD, I would say. Like, a couple of things have to go right. Number one, first, we have to really focus on the execution of these three opportunities for the patients that we serve. We gotta nail the NDA submissions, make sure we get strong labels and launch these three programs that we've been talking about. Secondly is we obviously have to correct our cost of capital and find a way to capture the value for the folks in this room and investors as we continue to make progress in the pipeline. Those two things have to come together for us to start to refocus on growth. I would say the opportunity has never been more exciting in the area of genetic disease as far as I'm concerned. Great. And a lot of interest from the audience on Disc Medicine's and EPP in particular. Maybe you could just elaborate on Gondola's EPP program and why you are so excited by that program and the early data that's been reported? Yeah. I would say, EPP is almost uniformly a disease of too much PPIX in the sera. As many people know, it arises typically from mutations in ferrochelatase in the red blood cell. Approaches that have been explored in the past, obviously Mitsubishi Tanabe Pharma Corporation and others have, quote-unquote, "tanning agents". The first disease-modifying approach was Disc Medicine's approach to inhibit glycine uptake into the red blood cell. Really we just, we looked at that and we tried to try to understand how we could do 1 better for the patient community. Couple of things that suffers from is a long time to depress PPIX levels in the sera. Second is, not as, not as profound a magnitude of depression as we think, is necessary, for optimal efficacy. The third is obviously where that compound hails from is schizophrenia and there's significant amounts of dizziness and some suicidal ideation as you get down into adolescence. We would have liked to have seen a more benign safety profile. The final thing that I think is underappreciated is this is a disease not only of phototoxicity, but also one that affects the liver. One would like a mechanism that could uniquely impact both the liver and the skin-associated phototoxicity. Our approach is actually to inhibit the egress of PPIX from the red blood cell by blocking its transporter, which is ABCG2. We have an inhibitor that we co-developed with a professor at University of Pittsburgh, and that has shown, as I presented earlier this year, profound both in terms of rapid descent of PPIX, up to 80% reduction in a Phase 2, and doing so very safely. We're excited about the profile. We also know that it affects the liver, and we've shown that in animal models. There'll be a longer-term clinical trial to prove that endpoint out. We're excited about that. The EOP2 meeting should be in about a month and a half, so we'll learn more about what the path forward there is. When you say rapid, how long is it taking to get to maximum reduction? Like, within two days versus the weeks that it takes for glycine uptake. Great. We have a minute left. Maybe in closing, Neil, I'll ask you what you believe is the most underappreciated aspect of the BridgeBio story by investors. I mean. Bless you. Traditionally, I would have probably pointed to one of LGMD2I or ADH1, to be honest. Honestly, the last couple days or last couple weeks, I feel like it is Atrubie. I feel like with the TAF IP overhang here, people are really discounting the potential for a brand that, to my eyes, is growing really nicely in a marketplace that continues to have significant unmet need and where we're cranking out really, really compelling clinical data. I'd start with Atrubie. Yeah. Great. With that, Neil, thanks for a great discussion. Thank you. Appreciate it

Speaker 2: All right, cool. Good afternoon, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thanks once again for joining us at TD Cowen's 46th Annual Healthcare Conference. For our next session, it's a privilege to have a fireside chat with BridgeBio, it's a pleasure to introduce Neil Kumar, the CEO of BridgeBio. Neil, thanks so much for joining me. All right, cool. all right cool Good afternoon, everyone. good afternoon everyone Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. tyler van buren here senior biotech analyst at td cowen Thanks once again for joining us at TD Cowen's 46th Annual Healthcare Conference. thanks once again for joining us at td cowen's 46th annual healthcare conference For our next session, it's a privilege to have a fireside chat with BridgeBio, it's a pleasure to introduce Neil Kumar, the CEO of BridgeBio. for our next session it's a privilege to have a fireside chat with bridgebio it's a pleasure to introduce neil kumar the ceo of bridgebio Neil, thanks so much for joining me. neil thanks so much for joining me

Speaker 1: Thanks. Thanks. thanks

Speaker 2: So, um- So, um- so um-

Speaker 1: Appreciate being here. Appreciate being here. appreciate being here

Speaker 2: What's that? What's that? what's that

Speaker 1: Appreciate being here. Appreciate being here. appreciate being here

Speaker 2: You got it. Look, Neil, the stock has corrected a little bit as of late after the huge run it had in the year prior. Personally believe it's a bit of kinda sell the news post ACON. Maybe some are just shorting it in the kinda near-term window ahead of the TAF IP trial and a lack of clinical data readouts. I don't think anything about the fundamentals of the story has really changed. They've continued to improve, obviously, with the 3 Phase 3 readouts. With that said, curious to get your perspective on that and your thoughts on the TAF IP situation as well, given that the trial's coming up here shortly. You got it. you got it Look, Neil, the stock has corrected a little bit as of late after the huge run it had in the year prior. look neil the stock has corrected a little bit as of late after the huge run it had in the year prior Personally believe it's a bit of kinda sell the news post ACON. personally believe it's a bit of kinda sell the news post acon Maybe some are just shorting it in the kinda near-term window ahead of the TAF IP trial and a lack of clinical data readouts. maybe some are just shorting it in the kinda near-term window ahead of the taf ip trial and a lack of clinical data readouts I don't think anything about the fundamentals of the story has really changed. i don't think anything about the fundamentals of the story has really changed They've continued to improve, obviously, with the 3 Phase 3 readouts. they've continued to improve obviously with the 3 phase 3 readouts With that said, curious to get your perspective on that and your thoughts on the TAF IP situation as well, given that the trial's coming up here shortly. with that said curious to get your perspective on that and your thoughts on the taf ip situation as well given that the trial's coming up here shortly

Speaker 1: Yeah, sure. Thanks for the question. Obviously, we've noted the pullback and the disconnect between intrinsic value and where the stock's trading now. I'd say first, we feel very privileged to be sitting on top of the last three phase threes, certainly in ADH1, LGMD2I, and the latest in achondroplasia. They all met or beat our expectations in terms of service to the patient communities, and we can go through the details of any of those, and I think that liberated a reasonable amount of intrinsic value, certainly in our models. Yeah, sure. yeah sure Thanks for the question. thanks for the question Obviously, we've noted the pullback and the disconnect between intrinsic value and where the stock's trading now. obviously we've noted the pullback and the disconnect between intrinsic value and where the stock's trading now I'd say first, we feel very privileged to be sitting on top of the last three phase threes, certainly in ADH1, LGMD2I, and the latest in achondroplasia. i'd say first we feel very privileged to be sitting on top of the last three phase threes certainly in adh1 lgmd2i and the latest in achondroplasia They all met or beat our expectations in terms of service to the patient communities, and we can go through the details of any of those, and I think that liberated a reasonable amount of intrinsic value, certainly in our models. they all met or beat our expectations in terms of service to the patient communities and we can go through the details of any of those and i think that liberated a reasonable amount of intrinsic value certainly in our models What's weighing on the stock, I think people in this room probably have a better idea than I do, but in large part what we've been hearing is it has to do with the TAF IP overhang. I'm not gonna make a huge deal out of it here. We tend not to talk publicly about our competitor's IP situation, but I obviously will say that the trial is upcoming in late April, and we believe Pfizer has very, very strong arguments both from the standpoint of infringement and from the standpoint of validity. What's weighing on the stock, I think people in this room probably have a better idea than I do, but in large part what we've been hearing is it has to do with the TAF IP overhang. I'm not gonna make a huge deal out of it here. what's weighing on the stock i think people in this room probably have a better idea than i do but in large part what we've been hearing is it has to do with the taf ip overhang i'm not gonna make a huge deal out of it here We tend not to talk publicly about our competitor's IP situation, but I obviously will say that the trial is upcoming in late April, and we believe Pfizer has very, very strong arguments both from the standpoint of infringement and from the standpoint of validity. we tend not to talk publicly about our competitor's ip situation but i obviously will say that the trial is upcoming in late april and we believe pfizer has very very strong arguments both from the standpoint of infringement and from the standpoint of validity Obviously Form I, lowest free energy form polymorph, we think it's well protected, and we think that it shows up in all the generic batches and otherwise Pfizer would not be basically asserting the claim against every single one of the generic manufacturers in our view. Again, I think they also have a very, very strong set of orthogonal methodologies that allow them to pick up Form I, obviously solid-state NMR, X-ray diffraction, as well as Raman spectroscopy. We feel good about that. Then on the validity standpoint, from the validity standpoint, which obviously has been a little bit more controversial given what happened in Europe, we really have to remember that in America, the bar is extraordinarily high for validity. Obviously Form I, lowest free energy form polymorph, we think it's well protected, and we think that it shows up in all the generic batches and otherwise Pfizer would not be basically asserting the claim against every single one of the generic manufacturers in our view. obviously form i lowest free energy form polymorph we think it's well protected and we think that it shows up in all the generic batches and otherwise pfizer would not be basically asserting the claim against every single one of the generic manufacturers in our view Again, I think they also have a very, very strong set of orthogonal methodologies that allow them to pick up Form I, obviously solid-state NMR, X-ray diffraction, as well as Raman spectroscopy. again i think they also have a very very strong set of orthogonal methodologies that allow them to pick up form i obviously solid-state nmr x-ray diffraction as well as raman spectroscopy We feel good about that. we feel good about that Then on the validity standpoint, from the validity standpoint, which obviously has been a little bit more controversial given what happened in Europe, we really have to remember that in America, the bar is extraordinarily high for validity. then on the validity standpoint from the validity standpoint which obviously has been a little bit more controversial given what happened in europe we really have to remember that in america the bar is extraordinarily high for validity If you're gonna make Form I, you gotta make it every single time that way, and then it's inherently anticipated. If even one or two times out of 100 you get something else, then it's not inherently anticipated. Because Pfizer did not document the acidification step in the context of Vyndamax, we believe, and you can see this from the fact that generics have been able to patent metastable or amorphous forms of the crystal, that you're not always gonna get Form I, and therefore we believe the patent is both non-infringible but also a valid patent. Again, that's our view. We'll leave it to Pfizer and others to sort that out. If you're gonna make Form I, you gotta make it every single time that way, and then it's inherently anticipated. if you're gonna make form i you gotta make it every single time that way and then it's inherently anticipated If even one or two times out of 100 you get something else, then it's not inherently anticipated. if even one or two times out of 100 you get something else then it's not inherently anticipated Because Pfizer did not document the acidification step in the context of Vyndamax, we believe, and you can see this from the fact that generics have been able to patent metastable or amorphous forms of the crystal, that you're not always gonna get Form I, and therefore we believe the patent is both non-infringible but also a valid patent. because pfizer did not document the acidification step in the context of vyndamax we believe and you can see this from the fact that generics have been able to patent metastable or amorphous forms of the crystal that you're not always gonna get form i and therefore we believe the patent is both non-infringible but also a valid patent Again, that's our view. again that's our view We'll leave it to Pfizer and others to sort that out. we'll leave it to pfizer and others to sort that out Our view is also that ATTR is a clinically differentiated molecule and in any circumstance we'll be able to continue to grow the brand for many years to come. Our view is also that ATTR is a clinically differentiated molecule and in any circumstance we'll be able to continue to grow the brand for many years to come. our view is also that attr is a clinically differentiated molecule and in any circumstance we'll be able to continue to grow the brand for many years to come

Speaker 2: Okay, great. Thanks for that. Trial starts in April, and presumably they need to come to some sort of ruling or decision by the November timeframe? Okay, great. okay great Thanks for that. thanks for that Trial starts in April, and presumably they need to come to some sort of ruling or decision by the November timeframe? trial starts in april and presumably they need to come to some sort of ruling or decision by the november timeframe

Speaker 1: Exactly, yeah. We expect to hear anywhere from late summer to November. Exactly, yeah. exactly yeah We expect to hear anywhere from late summer to November. we expect to hear anywhere from late summer to november

Speaker 2: Okay. Okay. okay

Speaker 1: I think honestly, in the first couple days of the trial, we'll have a sense as to whether or not they can assert those claims and really drive toward infringement for all the generic manufacturers. I think we'll have a sense here, end of April, be my guess. I think honestly, in the first couple days of the trial, we'll have a sense as to whether or not they can assert those claims and really drive toward infringement for all the generic manufacturers. i think honestly in the first couple days of the trial we'll have a sense as to whether or not they can assert those claims and really drive toward infringement for all the generic manufacturers I think we'll have a sense here, end of April, be my guess. i think we'll have a sense here end of april be my guess

Speaker 2: Regardless, there's gonna be an appeals process that plays out too, right? It'll be accelerated? Regardless, there's gonna be an appeals process that plays out too, right? regardless there's gonna be an appeals process that plays out too right It'll be accelerated? it'll be accelerated

Speaker 1: Not in the U.S., no. Not in the U.S., no. not in the u.s no

Speaker 2: Okay. Okay. okay

Speaker 1: Different. I mean, in Europe, what you have is you had the ruling, which obviously went in their favor, you had the appeals process with a couple scientists who took issue with the validity aspect with a different bar, probably a little different than the judge. Recall that they withdrew the patents at that point, there's no legal precedent that floats over to the U.S., but this will be the ruling of import. There will be no appeals process after that. Different. different I mean, in Europe, what you have is you had the ruling, which obviously went in their favor, you had the appeals process with a couple scientists who took issue with the validity aspect with a different bar, probably a little different than the judge. i mean in europe what you have is you had the ruling which obviously went in their favor you had the appeals process with a couple scientists who took issue with the validity aspect with a different bar probably a little different than the judge Recall that they withdrew the patents at that point, there's no legal precedent that floats over to the U.S., but this will be the ruling of import. recall that they withdrew the patents at that point there's no legal precedent that floats over to the u.s but this will be the ruling of import There will be no appeals process after that. there will be no appeals process after that

Speaker 2: Okay. All right. Pediatric exclusivity end of 2028, so earliest basically the generics are launching in 2029. If they do a 180-day exclusivity with single filer, could be, multiple generics later in 2029. Settlement would be like a 2032-2033 timeframe. The third scenario is the TAF IP holds up, and then that's 2035. Okay. okay All right. all right Pediatric exclusivity end of 2028, so earliest basically the generics are launching in 2029. pediatric exclusivity end of 2028 so earliest basically the generics are launching in 2029 If they do a 180-day exclusivity with single filer, could be, multiple generics later in 2029. if they do a 180-day exclusivity with single filer could be multiple generics later in 2029 Settlement would be like a 2032-2033 timeframe. settlement would be like a 2032-2033 timeframe The third scenario is the TAF IP holds up, and then that's 2035. the third scenario is the taf ip holds up and then that's 2035

Speaker 1: That's right. That's right. that's right

Speaker 2: Okay. Okay. okay

Speaker 1: By the way, we think that third scenario is highly probable based on what I just discussed. I know IPD and others believe the settlement in 32 to 33 is the most probable scenario, but we disagree. We're obviously not IP lawyers over here, so we'll just have to see how it plays out. I think it's important to note even past clinical differentiation that this is a Medi-D focused orphan drug space, and so obviously if you sort of break down the economics in the channel, patient co-pays are gonna stay the same whether you're on a generic or whether you're on a branded drug. Obviously all the distribution networks are gonna actually want branded, especially the ISPs. By the way, we think that third scenario is highly probable based on what I just discussed. by the way we think that third scenario is highly probable based on what i just discussed I know IPD and others believe the settlement in 32 to 33 is the most probable scenario, but we disagree. i know ipd and others believe the settlement in 32 to 33 is the most probable scenario but we disagree W e're obviously not IP lawyers over here, so we'll just have to see how it plays out. w e're obviously not ip lawyers over here so we'll just have to see how it plays out I think it's important to note even past clinical differentiation that this is a Medi-D focused orphan drug space, and so obviously if you sort of break down the economics in the channel, patient co-pays are gonna stay the same whether you're on a generic or whether you're on a branded drug. i think it's important to note even past clinical differentiation that this is a medi-d focused orphan drug space and so obviously if you sort of break down the economics in the channel patient co-pays are gonna stay the same whether you're on a generic or whether you're on a branded drug Obviously all the distribution networks are gonna actually want branded, especially the ISPs. obviously all the distribution networks are gonna actually want branded especially the isps I mean, we see this a lot in the context of academic medical centers. Ultimately, I think physicians are gonna wanna work with a branded distributor who is focused on doing hefty research like we are. I mean, I don't think anyone's running a primary prevention study like we are, a $400 million Act Early study. We've been doing a lot in real-world evidence. We've been doing a lot in subpopulations like the variant population, AFib population, and the like. I think we'll continue to try to differentiate the product and learn more about how small molecule stabilizers can be used to the benefit of patients overall, both earlier and in more severe settings. I mean, we see this a lot in the context of academic medical centers. i mean we see this a lot in the context of academic medical centers Ultimately, I think physicians are gonna wanna work with a branded distributor who is focused on doing hefty research like we are. ultimately i think physicians are gonna wanna work with a branded distributor who is focused on doing hefty research like we are I mean, I don't think anyone's running a primary prevention study like we are, a $400 million Act Early study. i mean i don't think anyone's running a primary prevention study like we are a $400 million act early study We've been doing a lot in real-world evidence. we've been doing a lot in real-world evidence We've been doing a lot in subpopulations like the variant population, AFib population, and the like. we've been doing a lot in subpopulations like the variant population afib population and the like I think we'll continue to try to differentiate the product and learn more about how small molecule stabilizers can be used to the benefit of patients overall, both earlier and in more severe settings. i think we'll continue to try to differentiate the product and learn more about how small molecule stabilizers can be used to the benefit of patients overall both earlier and in more severe settings

Speaker 2: Great. Now kind of staying at a high level, we have the ongoing Atrubie launch as well as the 3 NDA filings from the 3 positive phase 3s that just read out over the next year or two. Can you talk about your plan to manage expenses and cash runway all while continuing the Atrubie launch and these 3 new product launches? Great. great Now kind of staying at a high level, we have the ongoing Atrubie launch as well as the 3 NDA filings from the 3 positive phase 3s that just read out over the next year or two. now kind of staying at a high level we have the ongoing atrubie launch as well as the 3 nda filings from the 3 positive phase 3s that just read out over the next year or two Can you talk about your plan to manage expenses and cash runway all while continuing the Atrubie launch and these 3 new product launches? can you talk about your plan to manage expenses and cash runway all while continuing the atrubie launch and these 3 new product launches

Speaker 1: Yeah. I mean, I think, it's no surprise that every single one of these upcoming launches is gonna be materially cheaper than the Atrubie launch. Obviously, the field force for TTR is larger, plus we have an already established commercial infrastructure now. A lot of what you need to do for distribution design, patient services, certainly market access, incentives, sales force training, all of that stuff is already set up. Yeah, there will be an incremental tick-up in commercial spend. I think R&D will be flat to declining obviously as we bring some of these large phase threes off, and so we feel like we're very well-financed given the well over $1 billion that we have on the balance sheet, to get to profitability should we choose to do that. Yeah. yeah I mean, I think, it's no surprise that every single one of these upcoming launches is gonna be materially cheaper than the Atrubie launch. i mean i think it's no surprise that every single one of these upcoming launches is gonna be materially cheaper than the atrubie launch Obviously, the field force for TTR is larger, plus we have an already established commercial infrastructure now. obviously the field force for ttr is larger plus we have an already established commercial infrastructure now A lot of what you need to do for distribution design, patient services, certainly market access, incentives, sales force training, all of that stuff is already set up. a lot of what you need to do for distribution design patient services certainly market access incentives sales force training all of that stuff is already set up Yeah, there will be an incremental tick-up in commercial spend. yeah there will be an incremental tick-up in commercial spend I think R&D will be flat to declining obviously as we bring some of these large phase threes off, and so we feel like we're very well-financed given the well over $1 billion that we have on the balance sheet, to get to profitability should we choose to do that. i think r&d will be flat to declining obviously as we bring some of these large phase threes off and so we feel like we're very well-financed given the well over $1 billion that we have on the balance sheet to get to profitability should we choose to do that

Speaker 2: What sort of headcount and field footprint do you think these next three launches need? Maybe could put that into perspective relative to the Atrubie effort. What sort of headcount and field footprint do you think these next three launches need? what sort of headcount and field footprint do you think these next three launches need Maybe could put that into perspective relative to the Atrubie effort. maybe could put that into perspective relative to the atrubie effort

Speaker 1: Yeah, hard to tell. We've never really disclosed precisely the number of reps we have, I think, on TTR, but it's no surprise that one of our competitors has disclosed around 140. We're not that far off. That's probably a multiplier of 4 more than you need for something like a rare disease like LGMD2I or ADH1. Those will be small field forces. In fact, in some cases, I think the MSLs might be half the headcount of the actual field force. Yeah, hard to tell. yeah hard to tell We've never really disclosed precisely the number of reps we have, I think, on TTR, but it's no surprise that one of our competitors has disclosed around 140. we've never really disclosed precisely the number of reps we have i think on ttr but it's no surprise that one of our competitors has disclosed around 140 We're not that far off. we're not that far off That's probably a multiplier of 4 more than you need for something like a rare disease like LGMD2I or ADH1. that's probably a multiplier of 4 more than you need for something like a rare disease like lgmd2i or adh1 Those will be small field forces. those will be small field forces In fact, in some cases, I think the MSLs might be half the headcount of the actual field force. in fact in some cases i think the msls might be half the headcount of the actual field force

Speaker 2: Got it. What phase of preparations are you in for these 3 new launches? How ready are you guys to launch these products? Got it. got it What phase of preparations are you in for these 3 new launches? what phase of preparations are you in for these 3 new launches How ready are you guys to launch these products? how ready are you guys to launch these products

Speaker 1: All the commercial leaders have been hired. Medical affairs is out there for each, for each one of these pieces. Obviously, we, we're filing these NDAs, and we need to get approved before we can really turn on the gas. You're also able to send out your FRMs based on your phase 3 data and start to learn more about what pricing could look like. We're doing that as well. I would say everything we can do right now, appropriately, we are able to do. Very unlike actually in the context of an ATTR where we were so broke that when we hit, when we hit on that phase 3, we're like, "Oh, great." "Let's hire a commercial force. All the commercial leaders have been hired. all the commercial leaders have been hired Medical affairs is out there for each, for each one of these pieces. medical affairs is out there for each for each one of these pieces Obviously, we, we're filing these NDAs, and we need to get approved before we can really turn on the gas. obviously we we're filing these ndas and we need to get approved before we can really turn on the gas You're also able to send out your FRMs based on your phase 3 data and start to learn more about what pricing could look like. you're also able to send out your frms based on your phase 3 data and start to learn more about what pricing could look like We're doing that as well. we're doing that as well I would say everything we can do right now, appropriately, we are able to do. i would say everything we can do right now appropriately we are able to do Very unlike actually in the context of an ATTR where we were so broke that when we hit, when we hit on that phase 3, we're like, "Oh, great." "Let's hire a commercial force. very unlike actually in the context of an attr where we were so broke that when we hit when we hit on that phase 3 we're like "oh great." "let's hire a commercial force

Speaker 2: Moving to ATTR and acoramidis specifically, can you talk about the key factors driving the momentum today, the biggest contributors to the strength of the launch, and what gives you confidence that this is going to be a multi-year sustained growth of the franchise as opposed to just a strong first full year of launch? Moving to ATTR and acoramidis specifically, can you talk about the key factors driving the momentum today, the biggest contributors to the strength of the launch, and what gives you confidence that this is going to be a multi-year sustained growth of the franchise as opposed to just a strong first full year of launch? moving to attr and acoramidis specifically can you talk about the key factors driving the momentum today the biggest contributors to the strength of the launch and what gives you confidence that this is going to be a multi-year sustained growth of the franchise as opposed to just a strong first full year of launch

Speaker 1: Yeah. It's, pretty multifactorial. The strength actually, to me is indicated by that second derivative that's now gone positive again. You don't tend to see that as much in rare disease launches, at least as we modeled in our revenue institute. You see this explosion and then you kinda like, constant growth. The fact that we are, we're growing growth, if you will, quarter on quarter, and we're having basically the best couple quarters that we've had to date suggests a couple of things. One, I think we're doing a better job collectively as all the sponsors in the field in identifying patients and driving the call point, even outside of academic medical centers to high volume heart failure practices. Yeah. yeah It's, pretty multifactorial. it's pretty multifactorial The strength actually, to me is indicated by that second derivative that's now gone positive again. the strength actually to me is indicated by that second derivative that's now gone positive again You don't tend to see that as much in rare disease launches, at least as we modeled in our revenue institute. you don't tend to see that as much in rare disease launches at least as we modeled in our revenue institute You see this explosion and then you kinda like, constant growth. you see this explosion and then you kinda like constant growth The fact that we are, we're growing growth, if you will, quarter on quarter, and we're having basically the best couple quarters that we've had to date suggests a couple of things. the fact that we are we're growing growth if you will quarter on quarter and we're having basically the best couple quarters that we've had to date suggests a couple of things One, I think we're doing a better job collectively as all the sponsors in the field in identifying patients and driving the call point, even outside of academic medical centers to high volume heart failure practices. one i think we're doing a better job collectively as all the sponsors in the field in identifying patients and driving the call point even outside of academic medical centers to high volume heart failure practices We obviously haven't diagnosed even maybe 1/4 of the number of ATTR cardiomyopathy patients that almost certainly exist in the United States. That's work that needs to be done. I think, I was probably skeptical on this at first, but a large part of that is these sorts of AI, what people call AI, but it can sometimes be, a few factor sort of red flags that say, "Hey, consider this FF patient. They may have ATTR cardiomyopathy," and then that drives people to think of it and go to technetium scan. That's number one. We obviously haven't diagnosed even maybe 1/4 of the number of ATTR cardiomyopathy patients that almost certainly exist in the United States. we obviously haven't diagnosed even maybe 1/4 of the number of attr cardiomyopathy patients that almost certainly exist in the united states That's work that needs to be done. that's work that needs to be done I think, I was probably skeptical on this at first, but a large part of that is these sorts of AI , what people call AI, but it can sometimes be, a few factor sort of red flags that say, "Hey, consider this FF patient. i think i was probably skeptical on this at first but a large part of that is these sorts of ai what people call ai but it can sometimes be a few factor sort of red flags that say "hey consider this ff patient They may have ATTR cardiomyopathy," and then that drives people to think of it and go to technetium scan. they may have attr cardiomyopathy," and then that drives people to think of it and go to technetium scan That's number one. that's number one Number 2, I would say is the generation of additional clinical data, both in the context of the early separation, which I think is really starting to catch on and you should stay tuned for more research on why that is occurring, I think uniquely for our compound. But I think secondly and key in certain subpopulations, like the variant population where we had a 0.41 hazard ratio with stat sig, which is the best point estimate and statistical significance in the space. But also importantly, the AFib data. Recall, like almost I think 60% of patients or so on this channel have some cardiac arrhythmic involvement, and what people often will look at is the relative risk reduction or the 17% reduction. Number 2, I would say is the generation of additional clinical data, both in the context of the early separation, which I think is really starting to catch on and you should stay tuned for more research on why that is occurring, I think uniquely for our compound. number 2 i would say is the generation of additional clinical data both in the context of the early separation which i think is really starting to catch on and you should stay tuned for more research on why that is occurring i think uniquely for our compound But I think secondly and key in certain subpopulations, like the variant population where we had a 0.41 hazard ratio with stat sig, which is the best point estimate and statistical significance in the space. but i think secondly and key in certain subpopulations like the variant population where we had a 0.41 hazard ratio with stat sig which is the best point estimate and statistical significance in the space But also importantly, the AFib data. but also importantly the afib data Recall, like almost I think 60% of patients or so on this channel have some cardiac arrhythmic involvement, and what people often will look at is the relative risk reduction or the 17% reduction. recall like almost i think 60% of patients or so on this channel have some cardiac arrhythmic involvement and what people often will look at is the relative risk reduction or the 17% reduction Really what I think is most important is Atrubie works both in the context of AFib and in the context of non-AFib. If you're a prescriber in the field, especially outside of an academic medical center, you can prescribe Atrubie to all the patients that may have ATTR cardiomyopathy, and I think that significantly simplifies the script. Really what I think is most important is Atrubie works both in the context of AFib and in the context of non-AFib. really what i think is most important is atrubie works both in the context of afib and in the context of non-afib If you're a prescriber in the field, especially outside of an academic medical center, you can prescribe Atrubie to all the patients that may have ATTR cardiomyopathy, and I think that significantly simplifies the script. if you're a prescriber in the field especially outside of an academic medical center you can prescribe atrubie to all the patients that may have attr cardiomyopathy and i think that significantly simplifies the script

Speaker 2: Great. Is it fair to say you expect significant quarter-over-quarter growth each quarter this year? How do you think about the overall market opportunity? Do you think it has a real chance of becoming a $20 billion market? Great. great Is it fair to say you expect significant quarter-over-quarter growth each quarter this year? is it fair to say you expect significant quarter-over-quarter growth each quarter this year How do you think about the overall market opportunity? how do you think about the overall market opportunity Do you think it has a real chance of becoming a $20 billion market? do you think it has a real chance of becoming a $20 billion market

Speaker 1: Yeah, I do. I think, from a top-down perspective, there's still no study that suggests anything south of 12% of FF patients having ATTR cardiomyopathy. From that standpoint and the pricing stamp, coupled with where price is going, and where price is actually even today, I don't, I don't foresee there being an issue, getting to that size of market. I think from the bottom up, at least for us, we're seeing increasing education, we're seeing increasing prescription base in terms of number of prescribers. I think that that all portends continued growth. Yeah, I do. yeah i do I think, from a top-down perspective, there's still no study that suggests anything south of 12% of FF patients having ATTR cardiomyopathy. i think from a top-down perspective there's still no study that suggests anything south of 12% of ff patients having attr cardiomyopathy From that standpoint and the pricing stamp, coupled with where price is going, and where price is actually even today, I don't, I don't foresee there being an issue, getting to that size of market. from that standpoint and the pricing stamp coupled with where price is going and where price is actually even today i don't i don't foresee there being an issue getting to that size of market I think from the bottom up, at least for us, we're seeing increasing education, we're seeing increasing prescription base in terms of number of prescribers. i think from the bottom up at least for us we're seeing increasing education we're seeing increasing prescription base in terms of number of prescribers I think that that all portends continued growth. i think that that all portends continued growth

Speaker 2: What are you seeing, from a competitive standpoint in the market from both, Pfizer's franchise as well as Alnylam? Obviously, a different approach, in terms of the impact that it's having on your launch. Are you guys really, it just really comes down to your own execution, and you're kind of unimpeded in your launch? What are you seeing, from a competitive standpoint in the market from both, Pfizer's franchise as well as Alnylam? what are you seeing from a competitive standpoint in the market from both pfizer's franchise as well as alnylam Obviously, a different approach, in terms of the impact that it's having on your launch. obviously a different approach in terms of the impact that it's having on your launch Are you guys really, it just really comes down to your own execution, and you're kind of unimpeded in your launch? are you guys really it just really comes down to your own execution and you're kind of unimpeded in your launch

Speaker 1: I think a lot of this comes down to our own execution, to be honest. I feel like sometimes we're working all together as sponsors, to really grow the space. Each one of us have a different segment that I think we're strong in and, by and large, I would say, like, I mean, for instance, Pfizer just published two papers in JACC on the usefulness of serum TTR. That helps us because we obviously have a superior profile in terms of elevating serum TTR, but it reinforces to physicians the fact that for every mg per deciliter increase in serum TTR, you're getting about a 5% relative risk reduction in mortality at 30 months. I think a lot of this comes down to our own execution, to be honest. i think a lot of this comes down to our own execution to be honest I feel like sometimes we're working all together as sponsors, to really grow the space. i feel like sometimes we're working all together as sponsors to really grow the space Each one of us have a different segment that I think we're strong in and, by and large, I would say, like, I mean, for instance, Pfizer just published two papers in JACC on the usefulness of serum TTR. each one of us have a different segment that i think we're strong in and by and large i would say like i mean for instance pfizer just published two papers in jacc on the usefulness of serum ttr That helps us because we obviously have a superior profile in terms of elevating serum TTR, but it reinforces to physicians the fact that for every mg per deciliter increase in serum TTR, you're getting about a 5% relative risk reduction in mortality at 30 months. that helps us because we obviously have a superior profile in terms of elevating serum ttr but it reinforces to physicians the fact that for every mg per deciliter increase in serum ttr you're getting about a 5% relative risk reduction in mortality at 30 months Continuing to drive those types of stories into the marketplace, I think will be to the benefit of all medicines, but especially a superior stabilizer like ours. Continuing to drive those types of stories into the marketplace, I think will be to the benefit of all medicines, but especially a superior stabilizer like ours. continuing to drive those types of stories into the marketplace i think will be to the benefit of all medicines but especially a superior stabilizer like ours

Speaker 2: Bayer's getting a great early penetration in Europe with Beontra. Can you talk about the contribution of that ex US launch to the BridgeBio P&L and whether you expect that to start contributing this year or next year? Bayer's getting a great early penetration in Europe with Beontra. bayer's getting a great early penetration in europe with beontra Can you talk about the contribution of that ex US launch to the BridgeBio P&L and whether you expect that to start contributing this year or next year? can you talk about the contribution of that ex us launch to the bridgebio p&l and whether you expect that to start contributing this year or next year

Speaker 1: Yeah. I think this year it should start to contribute in a meaningful way, obviously, given the high royalties that we're a beneficiary of. I think Bayer's done a absolutely marvelous job of launching in Europe. Obviously, totally different commercial dynamics over there, and they've been able to secure a majority share in Germany and a few other marketplaces where we're actually the only drug in the national bid. Well, we're excited to see how they continue to grow the brand over there and to continue to learn from them in terms of how best to position our product here. Yeah. yeah I think this year it should start to contribute in a meaningful way, obviously, given the high royalties that we're a beneficiary of. i think this year it should start to contribute in a meaningful way obviously given the high royalties that we're a beneficiary of I think Bayer's done a absolutely marvelous job of launching in Europe. i think bayer's done a absolutely marvelous job of launching in europe Obviously, totally different commercial dynamics over there, and they've been able to secure a majority share in Germany and a few other marketplaces where we're actually the only drug in the national bid. obviously totally different commercial dynamics over there and they've been able to secure a majority share in germany and a few other marketplaces where we're actually the only drug in the national bid Well, we're excited to see how they continue to grow the brand over there and to continue to learn from them in terms of how best to position our product here. well we're excited to see how they continue to grow the brand over there and to continue to learn from them in terms of how best to position our product here

Speaker 2: Great. We gotta move to the 3 phase 3s that I've read out and the 3 new product launches. We'll start with infigratinib achondroplasia. Your recent data exceeded expectations on both efficacy and safety, really stellar data. I guess following the data that you reported, what's your latest assumptions in terms of potential market share that you could achieve relative to the injectables? Great. great We gotta move to the 3 phase 3s that I've read out and the 3 new product launches. we gotta move to the 3 phase 3s that i've read out and the 3 new product launches We'll start with infigratinib achondroplasia. we'll start with infigratinib achondroplasia Your recent data exceeded expectations on both efficacy and safety, really stellar data. your recent data exceeded expectations on both efficacy and safety really stellar data I guess following the data that you reported, what's your latest assumptions in terms of potential market share that you could achieve relative to the injectables? i guess following the data that you reported what's your latest assumptions in terms of potential market share that you could achieve relative to the injectables

Speaker 1: Yeah, I mean, we did a preference, share survey that I think I commented on in the last earnings call suggesting that we could get to 65%. I know the, most of the KOLs are saying something like 80%. I think just stepping back, I don't know what the right percentage is. We haven't done, the full degree of work yet, and we won't until we get the label. One of the things that's interesting is generally in a marketplace like this, it's probably 25% penetrated right now, and at least according to our market research, maybe 35% of patients in the United States are needle phobic, so they're not gonna be taking the existing products. Yeah, I mean, we did a preference, share survey that I think I commented on in the last earnings call suggesting that we could get to 65%. yeah i mean we did a preference share survey that i think i commented on in the last earnings call suggesting that we could get to 65% I know the, most of the KOLs are saying something like 80%. i know the most of the kols are saying something like 80% I think just stepping back, I don't know what the right percentage is. i think just stepping back i don't know what the right percentage is We haven't done, the full degree of work yet, and we won't until we get the label. we haven't done the full degree of work yet and we won't until we get the label One of the things that's interesting is generally in a marketplace like this, it's probably 25% penetrated right now, and at least according to our market research, maybe 35% of patients in the United States are needle phobic, so they're not gonna be taking the existing products. one of the things that's interesting is generally in a marketplace like this it's probably 25% penetrated right now and at least according to our market research maybe 35% of patients in the united states are needle phobic so they're not gonna be taking the existing products Our hope is that like many orals from Fabry to migraine, we both enlarge the TAM as well as take significant share from the existing products. I think the share taking would be associated with greater efficacy, a better safety profile, and obviously a more convenient profile as well. It really does feel like, this is a medicine that the community is excited to welcome and I think we should be off to the races with this launch. Our hope is that like many orals from Fabry to migraine, we both enlarge the TAM as well as take significant share from the existing products. our hope is that like many orals from fabry to migraine we both enlarge the tam as well as take significant share from the existing products I think the share taking would be associated with greater efficacy, a better safety profile, and obviously a more convenient profile as well. i think the share taking would be associated with greater efficacy a better safety profile and obviously a more convenient profile as well It really does feel like, this is a medicine that the community is excited to welcome and I think we should be off to the races with this launch. it really does feel like this is a medicine that the community is excited to welcome and i think we should be off to the races with this launch

Speaker 2: How large do you think this market is and, how does hypochondroplasia add to that? What are your expectations for infigratinib and hypochondroplasia? How large do you think this market is and, how does hypochondroplasia add to that? how large do you think this market is and how does hypochondroplasia add to that What are your expectations for infigratinib and hypochondroplasia? what are your expectations for infigratinib and hypochondroplasia

Speaker 1: Just as a reminder, hypochondroplasia is a similar hyperactivating mutation in FGFR3, the N540K mutation. It's a little less hyperactivating, and again, in animal models and cellular models, infigratinib targets this well-described condition at its source and is able to rectify not only the height symptomatology, but things beyond that. Our expectation is at this dose, which is a safe dose, obviously, we should be able to deliver best-in-class efficacy there as well, and we think that market is actually similarly sized to achondroplasia. Probably a little less well-defined, but similarly sized ultimately when you look at the statistical genetics. Just as a reminder, hypochondroplasia is a similar hyperactivating mutation in FGFR3, the N540K mutation. just as a reminder hypochondroplasia is a similar hyperactivating mutation in fgfr3 the n540k mutation It's a little less hyperactivating, and again, in animal models and cellular models, infigratinib targets this well-described condition at its source and is able to rectify not only the height symptomatology, but things beyond that. it's a little less hyperactivating and again in animal models and cellular models infigratinib targets this well-described condition at its source and is able to rectify not only the height symptomatology but things beyond that Our expectation is at this dose, which is a safe dose, obviously, we should be able to deliver best-in-class efficacy there as well, and we think that market is actually similarly sized to achondroplasia. our expectation is at this dose which is a safe dose obviously we should be able to deliver best-in-class efficacy there as well and we think that market is actually similarly sized to achondroplasia Probably a little less well-defined, but similarly sized ultimately when you look at the statistical genetics. probably a little less well-defined but similarly sized ultimately when you look at the statistical genetics

Speaker 2: Got it. Is it $5 billion potentially with Acon and hypochondroplasia combined? Got it. got it Is it $5 billion potentially with Acon and hypochondroplasia combined? is it $5 billion potentially with acon and hypochondroplasia combined

Speaker 1: Yeah. I think that's a rough sense. We haven't said anything about pricing yet, but, yeah, that would be roughly there. Yeah. yeah I think that's a rough sense. i think that's a rough sense We haven't said anything about pricing yet, but, yeah, that would be roughly there. we haven't said anything about pricing yet but yeah that would be roughly there

Speaker 2: Okay. Maybe just you could talk about the status of the hypochondroplasia trial, when we'll get the next data readout. Again, what expectations should be and also phase 3 start. Okay. okay Maybe just you could talk about the status of the hypochondroplasia trial, when we'll get the next data readout. maybe just you could talk about the status of the hypochondroplasia trial when we'll get the next data readout Again, what expectations should be and also phase 3 start. again what expectations should be and also phase 3 start

Speaker 1: Yeah. It's hard to tell precisely what the bar is. Yes, we haven't seen the bar from any of our competitors really. I'd say right now it would be statistically significant impact on the condition. You'll see data later this year, ultimately phase 3 starting next year. Yeah. Yeah. yeah It's hard to tell precisely what the bar is. it's hard to tell precisely what the bar is Yes, we haven't seen the bar from any of our competitors really. yes we haven't seen the bar from any of our competitors really I'd say right now it would be statistically significant impact on the condition. i'd say right now it would be statistically significant impact on the condition You'll see data later this year, ultimately phase 3 starting next year. you'll see data later this year ultimately phase 3 starting next year Yeah. yeah

Speaker 2: Okay. All right encaleret also exceeded expectations there. Maybe we could start again with. Actually encaleret and limb-girdle, let's discuss those kind of together. How do you think about the market sizes- Okay. okay All right e ncaleret also exceeded expectations there. all right e ncaleret also exceeded expectations there Maybe we could start again with. maybe we could start again with Actually encaleret and limb-girdle, let's discuss those kind of together. actually encaleret and limb-girdle let's discuss those kind of together How do you think about the market sizes- how do you think about the market sizes-

Speaker 1: The two forgotten products? The two forgotten products? the two forgotten products

Speaker 2: Yeah, exactly. For both of those programs. You know, if you had to pick, one of your children, which one would you pick? Which one, which market opportunity or launch are you most excited about? Yeah, exactly. yeah exactly For both of those programs. for both of those programs You know, if you had to pick, one of your children, which one would you pick? you know if you had to pick one of your children which one would you pick Which one, which market opportunity or launch are you most excited about? which one which market opportunity or launch are you most excited about

Speaker 1: I'm excited for both, to be honest. I mean, I think two very different profiles. On LGMD2I, the one thing I would point out is if folks call around to muscular dystrophy clinics right now, there's a reasonable number of patients that are already identified. You could see that through natural history. It's also congruent with how quickly the trial enrolled, given the prevalence. We think there's maybe 1,200-1,300 patients in the U.S. and a lot of them are already identified. I think that launch is gonna be premium priced and go fairly quickly if we can serve those patients, well, as quickly as possible, I think that's what we'd be intending to do. ADH1 a little different. I'm excited for both, to be honest. i'm excited for both to be honest I mean, I think two very different profiles. i mean i think two very different profiles On LGMD2I, the one thing I would point out is if folks call around to muscular dystrophy clinics right now, there's a reasonable number of patients that are already identified. on lgmd2i the one thing i would point out is if folks call around to muscular dystrophy clinics right now there's a reasonable number of patients that are already identified You could see that through natural history. you could see that through natural history It's also congruent with how quickly the trial enrolled, given the prevalence. it's also congruent with how quickly the trial enrolled given the prevalence We think there's maybe 1,200-1,300 patients in the U.S. and a lot of them are already identified. we think there's maybe 1,200-1,300 patients in the u.s and a lot of them are already identified I think that launch is gonna be premium priced and go fairly quickly if we can serve those patients, well, as quickly as possible, I think that's what we'd be intending to do. i think that launch is gonna be premium priced and go fairly quickly if we can serve those patients well as quickly as possible i think that's what we'd be intending to do ADH1 a little different. adh1 a little different Obviously, the statistical genetic prevalence is massive, 10,000-12,000 in the United States alone, that is not the number of identified patients. You know, we think that there's maybe 2,000-3,000 hyper symptomatic identified patients right now. We've rolled out a genetic testing program that I discussed at someone else's conference that we continue to build upon in the non-surgical hypoparathyroidism community to find more and more of those patients that are really hiding within that space with hyperactivating mutations, the CASR. I think that actually launch will be kind of a slower build, ultimately we'll get to similar peakier sales. Obviously, the statistical genetic prevalence is massive, 10,000-12,000 in the United States alone, that is not the number of identified patients. obviously the statistical genetic prevalence is massive 10,000-12,000 in the united states alone that is not the number of identified patients You know, we think that there's maybe 2,000-3,000 hyper symptomatic identified patients right now. you know we think that there's maybe 2,000-3,000 hyper symptomatic identified patients right now We've rolled out a genetic testing program that I discussed at someone else's conference that we continue to build upon in the non-surgical hypoparathyroidism community to find more and more of those patients that are really hiding within that space with hyperactivating mutations, the CASR. we've rolled out a genetic testing program that i discussed at someone else's conference that we continue to build upon in the non-surgical hypoparathyroidism community to find more and more of those patients that are really hiding within that space with hyperactivating mutations the casr I think that actually launch will be kind of a slower build, ultimately we'll get to similar peakier sales. i think that actually launch will be kind of a slower build ultimately we'll get to similar peakier sales

Speaker 2: Maybe you could just elaborate on that genetic testing program, how you expect it to progress, and how you expect to diagnose these additional patients? Maybe you could just elaborate on that genetic testing program, how you expect it to progress, and how you expect to diagnose these additional patients? maybe you could just elaborate on that genetic testing program how you expect it to progress and how you expect to diagnose these additional patients

Speaker 1: Yeah. About, 130 different hyperactivating mutations in the calcium-sensing receptor. We know what they are. We've characterized them. We published a paper on this last year that I think you and I discussed. We've got a panel, and what we can do is we can offer that panel at cost to a prescribing physician, potentially prescribing physicians in the future. Today, physicians that just wanna understand better what the genesis of calcium-induced regulation might be in, let's say, a hypoparathyroidism patient or someone who's you sort of classified as a hypoparathyroidism patient today. Yeah. yeah About, 130 different hyperactivating mutations in the calcium-sensing receptor. about 130 different hyperactivating mutations in the calcium-sensing receptor We know what they are. we know what they are We've characterized them. we've characterized them We published a paper on this last year that I think you and I discussed. we published a paper on this last year that i think you and i discussed We've got a panel, and what we can do is we can offer that panel at cost to a prescribing physician, potentially prescribing physicians in the future. we've got a panel and what we can do is we can offer that panel at cost to a prescribing physician potentially prescribing physicians in the future Today, physicians that just wanna understand better what the genesis of calcium-induced regulation might be in, let's say, a hypoparathyroidism patient or someone who's you sort of classified as a hypoparathyroidism patient today. today physicians that just wanna understand better what the genesis of calcium-induced regulation might be in let's say a hypoparathyroidism patient or someone who's you sort of classified as a hypoparathyroidism patient today

Speaker 2: Is it fair to say that, both of these opportunities, ADH1 and Limb-girdle are billion-dollar-plus opportunities in your view? Is it fair to say that, both of these opportunities, ADH1 and Limb-girdle are billion-dollar-plus opportunities in your view? is it fair to say that both of these opportunities adh1 and limb-girdle are billion-dollar-plus opportunities in your view

Speaker 1: Yeah, I would think so. That's, I would say for LGMD2I, it's not obvious what the additional indications might be associated with BBP-418. There's Fukuyama syndrome, ISPD mutations, but there's not a whole lot else in that pathway. It's interesting to speculate as to whether or not hyperglycosylation of the complex might be relevant in the context of some other muscular dystrophies, but we haven't seen a genetic signal therein yet. I think that's one piece of it. On ADH1, obviously, we'll be kicking off a phase 3 in chronic hypoparathyroid, I think that is another very large opportunity for us. Yeah, I would think so. yeah i would think so That's, I would say for LGMD2I, it's not obvious what the additional indications might be associated with BBP-418. that's i would say for lgmd2i it's not obvious what the additional indications might be associated with bbp-418 There's Fukuyama syndrome, ISPD mutations, but there's not a whole lot else in that pathway. there's fukuyama syndrome ispd mutations but there's not a whole lot else in that pathway It's interesting to speculate as to whether or not hyperglycosylation of the complex might be relevant in the context of some other muscular dystrophies, but we haven't seen a genetic signal therein yet. it's interesting to speculate as to whether or not hyperglycosylation of the complex might be relevant in the context of some other muscular dystrophies but we haven't seen a genetic signal therein yet I think that's one piece of it. i think that's one piece of it On ADH1, obviously, we'll be kicking off a phase 3 in chronic hypoparathyroid, I think that is another very large opportunity for us. on adh1 obviously we'll be kicking off a phase 3 in chronic hypoparathyroid i think that is another very large opportunity for us That could be $1 billion, could be well over $1 billion if we hit on that phase 3. That could be $1 billion, could be well over $1 billion if we hit on that phase 3. that could be $1 billion could be well over $1 billion if we hit on that phase 3

Speaker 2: Yep. Yeah, the Phase 3 RECLAIM-HP study in hypoparathyroidism. Maybe you could just reiterate both what you saw in Phase 2 and also mechanistically why you have such confidence in Encalaret in hypoparathyroidism. Yep. yep Yeah, the Phase 3 RECLAIM-HP study in hypoparathyroidism. yeah the phase 3 reclaim-hp study in hypoparathyroidism Maybe you could just reiterate both what you saw in Phase 2 and also mechanistically why you have such confidence in Encalaret in hypoparathyroidism. maybe you could just reiterate both what you saw in phase 2 and also mechanistically why you have such confidence in encalaret in hypoparathyroidism

Speaker 1: Yeah, it's a little different than our normal approach, right? Typically we start with pathomechanism, and we try to target the well-described condition at its source. Here, we were looking at the phenotype of the drug, if you will, and trying to match it up with an unmet need. In the context of chronic hypoparathyroidism, it's obviously a disease that's solely about calcium dysregulation, but it stems from a lack of PTH. Giving back PTH would make sense, and that's obviously what our competitors do. There are some issues with that long term in terms of bone abnormalities because you're not doing it in a physiologic way. Yeah, it's a little different than our normal approach, right? yeah it's a little different than our normal approach right Typically we start with pathomechanism, and we try to target the well-described condition at its source. typically we start with pathomechanism and we try to target the well-described condition at its source Here, we were looking at the phenotype of the drug, if you will, and trying to match it up with an unmet need. here we were looking at the phenotype of the drug if you will and trying to match it up with an unmet need In the context of chronic hypoparathyroidism, it's obviously a disease that's solely about calcium dysregulation, but it stems from a lack of PTH. in the context of chronic hypoparathyroidism it's obviously a disease that's solely about calcium dysregulation but it stems from a lack of pth Giving back PTH would make sense, and that's obviously what our competitors do. giving back pth would make sense and that's obviously what our competitors do There are some issues with that long term in terms of bone abnormalities because you're not doing it in a physiologic way. there are some issues with that long term in terms of bone abnormalities because you're not doing it in a physiologic way When we look at our drug, what we realized was we were able to normalize urine and serum calcium through antagonism of the calcium-sensing receptor and to do it in a PTH-independent way through really the action of the kidney. That's what got us excited about exploring the agent in that space. We did a, I hesitate to call it a phase 2. It was really a signal-seeking 10-patient study, but what we saw was 80% normalization of urine and serum calcium in the context of chronic hypoparathyroidism patients. That's what gave us the confidence to really move it into phase 3 aggressively. It would be the only oral agent. I think it would be actually something that the community would welcome if we're able to deliver on the promise of the phase 2 or signal-seeking study. When we look at our drug, what we realized was we were able to normalize urine and serum calcium through antagonism of the calcium-sensing receptor and to do it in a PTH-independent way through really the action of the kidney. when we look at our drug what we realized was we were able to normalize urine and serum calcium through antagonism of the calcium-sensing receptor and to do it in a pth-independent way through really the action of the kidney That's what got us excited about exploring the agent in that space. that's what got us excited about exploring the agent in that space We did a, I hesitate to call it a phase 2. we did a i hesitate to call it a phase 2 It was really a signal-seeking 10-patient study, but what we saw was 80% normalization of urine and serum calcium in the context of chronic hypoparathyroidism patients. it was really a signal-seeking 10-patient study but what we saw was 80% normalization of urine and serum calcium in the context of chronic hypoparathyroidism patients That's what gave us the confidence to really move it into phase 3 aggressively. that's what gave us the confidence to really move it into phase 3 aggressively It would be the only oral agent. it would be the only oral agent I think it would be actually something that the community would welcome if we're able to deliver on the promise of the phase 2 or signal-seeking study. i think it would be actually something that the community would welcome if we're able to deliver on the promise of the phase 2 or signal-seeking study

Speaker 2: I guess just to follow up on that, you think mechanistically there's a chance that it could be superior to the PTH analogs in hypoparathyroidism? I guess just to follow up on that, you think mechanistically there's a chance that it could be superior to the PTH analogs in hypoparathyroidism? i guess just to follow up on that you think mechanistically there's a chance that it could be superior to the pth analogs in hypoparathyroidism

Speaker 1: I mean, I think it would Mechanistically, it should be able to deliver better urine normalization, urine calcium normalization, and it should be safer. It's oral. At the very least, it should be competitive. I mean, I think it would Mechanistically, it should be able to deliver better urine normalization, urine calcium normalization, and it should be safer. i mean i think it would mechanistically it should be able to deliver better urine normalization urine calcium normalization and it should be safer It's oral. it's oral At the very least, it should be competitive. at the very least it should be competitive

Speaker 2: Great. when the ADH1 data came out, some folks were like, "The PTH analogs can treat ADH1 patients." Curious to get your thoughts on that if currently ADH1 patients are being treated by Aurba or Natpara? Great. when the ADH1 data came out, some folks were like, "The PTH analogs can treat ADH1 patients." Curious to get your thoughts on that if currently ADH1 patients are being treated by Aurba or Natpara? great when the adh1 data came out some folks were like "the pth analogs can treat adh1 patients." curious to get your thoughts on that if currently adh1 patients are being treated by aurba or natpara

Speaker 1: No. Almost none of them are to be honest. There was that very small study that was published in The New England Journal, suggesting, inferior levels, obviously of urine calcium normalization. I don't think it'll be competitive in the context of ADH1. No. no Almost none of them are to be honest. almost none of them are to be honest There was that very small study that was published in The New England Journal, suggesting, inferior levels, obviously of urine calcium normalization. there was that very small study that was published in the new england journal suggesting inferior levels obviously of urine calcium normalization I don't think it'll be competitive in the context of ADH1. i don't think it'll be competitive in the context of adh1

Speaker 2: Great. Okay. All right. Just, on going back to limb-girdle, can you elaborate on those conversations with the FDA where they supported a traditional full approval with the NDA, and how those conversations went? Great. great Okay. okay All right. all right Just, on going back to limb-girdle, can you elaborate on those conversations with the FDA where they supported a traditional full approval with the NDA, and how those conversations went? just on going back to limb-girdle can you elaborate on those conversations with the fda where they supported a traditional full approval with the nda and how those conversations went

Speaker 1: I mean, I would say that, generally, this division is not seeing a whole lot of datasets that were as uniformly consistent. When I say uniform consistency, I would talk about 2 real measures of it. Number 1 is across different functional outcomes and inclusive of modified North Star, which I think was quite surprising, even to us and heartening. Then the second is across subpopulations. heterozygous, compound heterozygotes and L276I, old and young, ambulatory, non-ambulatory. I think all of those things together, it really the agency is looking for that level of consistency to make sure it's not outliers driven. I mean, I would say that, generally, this division is not seeing a whole lot of datasets that were as uniformly consistent. i mean i would say that generally this division is not seeing a whole lot of datasets that were as uniformly consistent When I say uniform consistency, I would talk about 2 real measures of it. when i say uniform consistency i would talk about 2 real measures of it Number 1 is across different functional outcomes and inclusive of modified North Star, which I think was quite surprising, even to us and heartening. number 1 is across different functional outcomes and inclusive of modified north star which i think was quite surprising even to us and heartening Then the second is across subpopulations. heterozygous, compound heterozygotes and L276I, old and young, ambulatory, non-ambulatory. then the second is across subpopulations heterozygous compound heterozygotes and l276i old and young ambulatory non-ambulatory I think all of those things together, it really the agency is looking for that level of consistency to make sure it's not outliers driven. i think all of those things together it really the agency is looking for that level of consistency to make sure it's not outliers driven It's, a true statistically significant impact, and that's, I think, what all led to, the enthusiasm around submitting for full approval. It's, a true statistically significant impact, and that's, I think, what all led to, the enthusiasm around submitting for full approval. it's a true statistically significant impact and that's i think what all led to the enthusiasm around submitting for full approval

Speaker 2: I guess just to round it out for both of these, indications and potential launches, ADH1 and Limb-girdle, based upon your filing timelines, you guys could be launching both of these drugs in the first half of next year. I guess just to round it out for both of these, indications and potential launches, ADH1 and Limb-girdle, based upon your filing timelines, you guys could be launching both of these drugs in the first half of next year. i guess just to round it out for both of these indications and potential launches adh1 and limb-girdle based upon your filing timelines you guys could be launching both of these drugs in the first half of next year

Speaker 1: Yeah, that's right. Yeah, that's right. yeah that's right

Speaker 2: Okay. infigratinib for achondroplasia obviously would be after that next year. Okay. infigratinib for achondroplasia obviously would be after that next year. okay infigratinib for achondroplasia obviously would be after that next year

Speaker 1: Yeah. I think the first half of next year is doable as well, but let's see. Yeah. yeah I think the first half of next year is doable as well, but let's see. i think the first half of next year is doable as well but let's see

Speaker 2: Okay. How do you think about, again, balancing executing on these launches and building out the pipeline? What might we see from the internal pipeline over the next year or two, as well as, potential external opportunities? Okay. okay How do you think about, again, balancing executing on these launches and building out the pipeline? how do you think about again balancing executing on these launches and building out the pipeline What might we see from the internal pipeline over the next year or two, as well as, potential external opportunities? what might we see from the internal pipeline over the next year or two as well as potential external opportunities

Speaker 1: Yeah. I mean, I when I talk about the external pipeline, I include our sister companies and probably most relevantly, Gondobio. Within that, I think we have a vast array of technologies that we're working with. Obviously, we've talked about what we think is a best-in-class EPP program. We have two other clinical programs, one in CMT1A, one in alpha-1 antitrypsin. We have some seven development candidates that we think we'll hit on varying from TSC and rev inhibition to a novel mechanism in the context of ADPKD. Yeah. yeah I mean, I when I talk about the external pipeline, I include our sister companies and probably most relevantly, Gondobio. i mean i when i talk about the external pipeline i include our sister companies and probably most relevantly gondobio Within that, I think we have a vast array of technologies that we're working with. within that i think we have a vast array of technologies that we're working with Obviously, we've talked about what we think is a best-in-class EPP program. obviously we've talked about what we think is a best-in-class epp program We have two other clinical programs, one in CMT1A, one in alpha-1 antitrypsin. we have two other clinical programs one in cmt1a one in alpha-1 antitrypsin We have some seven development candidates that we think we'll hit on varying from TSC and rev inhibition to a novel mechanism in the context of ADPKD. we have some seven development candidates that we think we'll hit on varying from tsc and rev inhibition to a novel mechanism in the context of adpkd There's a lot to be done, and I think we've already proven that we have a very efficient late-stage development, and hopefully, we will prove that we have a very efficient commercial engine that can be deployed at scale at BridgeBio. Bringing all these things together makes a ton of sense. Timing of that is TBD, I would say. Like, a couple of things have to go right. Number one, first, we have to really focus on the execution of these three opportunities for the patients that we serve. We gotta nail the NDA submissions, make sure we get strong labels and launch these three programs that we've been talking about. There's a lot to be done, and I think we've already proven that we have a very efficient late-stage development, and hopefully, we will prove that we have a very efficient commercial engine that can be deployed at scale at BridgeBio. there's a lot to be done and i think we've already proven that we have a very efficient late-stage development and hopefully we will prove that we have a very efficient commercial engine that can be deployed at scale at bridgebio Bringing all these things together makes a ton of sense. bringing all these things together makes a ton of sense Timing of that is TBD, I would say. timing of that is tbd i would say Like, a couple of things have to go right. like a couple of things have to go right Number one, first, we have to really focus on the execution of these three opportunities for the patients that we serve. number one first we have to really focus on the execution of these three opportunities for the patients that we serve We gotta nail the NDA submissions, make sure we get strong labels and launch these three programs that we've been talking about. we gotta nail the nda submissions make sure we get strong labels and launch these three programs that we've been talking about Secondly is we obviously have to correct our cost of capital and find a way to capture the value for the folks in this room and investors as we continue to make progress in the pipeline. Those two things have to come together for us to start to refocus on growth. I would say the opportunity has never been more exciting in the area of genetic disease as far as I'm concerned. Secondly is we obviously have to correct our cost of capital and find a way to capture the value for the folks in this room and investors as we continue to make progress in the pipeline. secondly is we obviously have to correct our cost of capital and find a way to capture the value for the folks in this room and investors as we continue to make progress in the pipeline Those two things have to come together for us to start to refocus on growth. those two things have to come together for us to start to refocus on growth I would say the opportunity has never been more exciting in the area of genetic disease as far as I'm concerned. i would say the opportunity has never been more exciting in the area of genetic disease as far as i'm concerned

Speaker 2: Great. And a lot of interest from the audience on Disc Medicine's and EPP in particular. Maybe you could just elaborate on Gondola's EPP program and why you are so excited by that program and the early data that's been reported? Great. great And a lot of interest from the audience on Disc Medicine's and EPP in particular. and a lot of interest from the audience on disc medicine's and epp in particular Maybe you could just elaborate on Gondola's EPP program and why you are so excited by that program and the early data that's been reported? maybe you could just elaborate on gondola's epp program and why you are so excited by that program and the early data that's been reported

Speaker 1: Yeah. I would say, EPP is almost uniformly a disease of too much PPIX in the sera. As many people know, it arises typically from mutations in ferrochelatase in the red blood cell. Approaches that have been explored in the past, obviously Mitsubishi Tanabe Pharma Corporation and others have, quote-unquote, "tanning agents". The first disease-modifying approach was Disc Medicine's approach to inhibit glycine uptake into the red blood cell. Really we just, we looked at that and we tried to try to understand how we could do 1 better for the patient community. Couple of things that suffers from is a long time to depress PPIX levels in the sera. Yeah. yeah I would say, EPP is almost uniformly a disease of too much PPIX in the sera. i would say epp is almost uniformly a disease of too much ppix in the sera As many people know, it arises typically from mutations in ferrochelatase in the red blood cell. as many people know it arises typically from mutations in ferrochelatase in the red blood cell Approaches that have been explored in the past, obviously Mitsubishi Tanabe Pharma Corporation and others have, quote-unquote, "tanning agents". approaches that have been explored in the past obviously mitsubishi tanabe pharma corporation and others have quote-unquote "tanning agents" The first disease-modifying approach was Disc Medicine's approach to inhibit glycine uptake into the red blood cell. the first disease-modifying approach was disc medicine's approach to inhibit glycine uptake into the red blood cell Really we just, we looked at that and we tried to try to understand how we could do 1 better for the patient community. really we just we looked at that and we tried to try to understand how we could do 1 better for the patient community Couple of things that suffers from is a long time to depress PPIX levels in the sera. couple of things that suffers from is a long time to depress ppix levels in the sera Second is, not as, not as profound a magnitude of depression as we think, is necessary, for optimal efficacy. The third is obviously where that compound hails from is schizophrenia and there's significant amounts of dizziness and some suicidal ideation as you get down into adolescence. We would have liked to have seen a more benign safety profile. The final thing that I think is underappreciated is this is a disease not only of phototoxicity, but also one that affects the liver. One would like a mechanism that could uniquely impact both the liver and the skin-associated phototoxicity. Our approach is actually to inhibit the egress of PPIX from the red blood cell by blocking its transporter, which is ABCG2. Second is, not as, not as profound a magnitude of depression as we think, is necessary, for optimal efficacy. second is not as not as profound a magnitude of depression as we think is necessary for optimal efficacy The third is obviously where that compound hails from is schizophrenia and there's significant amounts of dizziness and some suicidal ideation as you get down into adolescence. the third is obviously where that compound hails from is schizophrenia and there's significant amounts of dizziness and some suicidal ideation as you get down into adolescence We would have liked to have seen a more benign safety profile. we would have liked to have seen a more benign safety profile The final thing that I think is underappreciated is this is a disease not only of phototoxicity, but also one that affects the liver. the final thing that i think is underappreciated is this is a disease not only of phototoxicity but also one that affects the liver One would like a mechanism that could uniquely impact both the liver and the skin-associated phototoxicity. one would like a mechanism that could uniquely impact both the liver and the skin-associated phototoxicity Our approach is actually to inhibit the egress of PPIX from the red blood cell by blocking its transporter, which is ABCG2. our approach is actually to inhibit the egress of ppix from the red blood cell by blocking its transporter which is abcg2 We have an inhibitor that we co-developed with a professor at University of Pittsburgh, and that has shown, as I presented earlier this year, profound both in terms of rapid descent of PPIX, up to 80% reduction in a Phase 2, and doing so very safely. We're excited about the profile. We also know that it affects the liver, and we've shown that in animal models. There'll be a longer-term clinical trial to prove that endpoint out. We're excited about that. The EOP2 meeting should be in about a month and a half, so we'll learn more about what the path forward there is. We have an inhibitor that we co-developed with a professor at University of Pittsburgh, and that has shown, as I presented earlier this year, profound both in terms of rapid descent of PPIX, up to 80% reduction in a Phase 2, and doing so very safely. we have an inhibitor that we co-developed with a professor at university of pittsburgh and that has shown as i presented earlier this year profound both in terms of rapid descent of ppix up to 80% reduction in a phase 2 and doing so very safely We're excited about the profile. we're excited about the profile We also know that it affects the liver, and we've shown that in animal models. we also know that it affects the liver and we've shown that in animal models There'll be a longer-term clinical trial to prove that endpoint out. there'll be a longer-term clinical trial to prove that endpoint out We're excited about that. we're excited about that The EOP2 meeting should be in about a month and a half, so we'll learn more about what the path forward there is. the eop2 meeting should be in about a month and a half so we'll learn more about what the path forward there is

Speaker 2: When you say rapid, how long is it taking to get to maximum reduction? When you say rapid, how long is it taking to get to maximum reduction? when you say rapid how long is it taking to get to maximum reduction

Speaker 1: Like, within two days versus the weeks that it takes for glycine uptake. Like, within two days versus the weeks that it takes for glycine uptake. like within two days versus the weeks that it takes for glycine uptake

Speaker 2: Great. We have a minute left. Maybe in closing, Neil, I'll ask you what you believe is the most underappreciated aspect of the BridgeBio story by investors. Great. great We have a minute left. we have a minute left Maybe in closing, Neil, I'll ask you what you believe is the most underappreciated aspect of the BridgeBio story by investors. maybe in closing neil i'll ask you what you believe is the most underappreciated aspect of the bridgebio story by investors

Speaker 1: I mean. Bless you. Traditionally, I would have probably pointed to one of LGMD2I or ADH1, to be honest. Honestly, the last couple days or last couple weeks, I feel like it is Atrubie. I feel like with the TAF IP overhang here, people are really discounting the potential for a brand that, to my eyes, is growing really nicely in a marketplace that continues to have significant unmet need and where we're cranking out really, really compelling clinical data. I'd start with Atrubie. Yeah. I mean. i mean Bless you. bless you Traditionally, I would have probably pointed to one of LGMD2I or ADH1, to be honest. traditionally i would have probably pointed to one of lgmd2i or adh1 to be honest Honestly, the last couple days or last couple weeks, I feel like it is Atrubie. honestly the last couple days or last couple weeks i feel like it is atrubie I feel like with the TAF IP overhang here, people are really discounting the potential for a brand that, to my eyes, is growing really nicely in a marketplace that continues to have significant unmet need and where we're cranking out really, really compelling clinical data. i feel like with the taf ip overhang here people are really discounting the potential for a brand that to my eyes is growing really nicely in a marketplace that continues to have significant unmet need and where we're cranking out really really compelling clinical data I'd start with Atrubie. i'd start with atrubie Yeah. yeah

Speaker 2: Great. With that, Neil, thanks for a great discussion. Great. great With that, Neil, thanks for a great discussion. with that neil thanks for a great discussion

Speaker 1: Thank you. Thank you. thank you Appreciate it Appreciate it appreciate it