BridgeBio Pharma, Inc. (BBIO) Earnings Call Transcript & Summary

All right. Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Joyce Zhou and Rati Pinge. Kicking off the conference, we have BridgeBio. And then presenting on behalf of the company, we have CEO, Neil Kumar. Neil?

Well, thanks, everyone, for taking the time this morning. I'd like to thank Mike, Ben and the entire JPMorgan team for having us here again this year. This morning, I was reminded that BridgeBio turns 10 this year. And for a vast majority of those years, we've had the absolute privilege of being pajooled, challenged, and sometimes supported by the man to the left at me here, Anupam. So thank you for the partnership through the years, Anup. Maybe I'll continue in that vein of thinking and thank all of the investors, both in the room and on the line for the support over the last decade. Together, we have created the second, or third most efficient R&D engine for patients suffering with genetic diseases. Three approved products to date with hopefully three more to come in the next 12 months. Almost 20 INDs generated and most importantly, nearly 10,000 patient lives affected, with hopefully many tens of thousands of more to come in the coming years and decade. But you didn't come here this morning to hear me talk about the past. You came to hear me talk about where we're going and where we're headed over the coming weeks, months and years. And for that, we continue to believe that it is day 1 in this era of genetic medicine. And I'll give you updates today, all new information across the 3 different stages of our business. First and importantly, our commercial franchise in ATTR cardiomyopathy. Second, updates both on the data front and regulatory front for our late-stage franchises in achondroplasia, LGMB2I, ADH1 and Canavan disease. And then finally, I'll touch on some of that early-stage research substrate that's exciting us so much, and give you a good example of some of the early-stage research we're doing with our EPP, potentially best-in-class asset, that just cleared its Phase IIa. But let me start with the most important slide in this document. We are preannouncing today our Q4 revenue number of $146 million. And the reason we get excited about this number is that it suggests we are helping ever higher numbers of patients with ever more numbers of physician partners. $146 million of revenue is a 35% growth over our last quarter, and suggest about a 60% CAGR. And just as another reminder, this is actually more revenue generated in the fourth quarter of launch than tafamidis generated as it came out of the gates. This brings our total in our first 4 quarters of revenue to $362 million. And even more heartening than this number are the numbers that lie underneath it. Some 6,629 unique U.S. patients that we've been able to serve with Attruby in partnership with over 1,600 physicians. And as you all know, we focus greatly on NBRx share. NBRx share, given the dynamics in this commercial marketplace, we believe, is suggestive of ultimate TRx, our goal being 30% to 35% peak year share by volume. We're well on our way with greater than 25% NBRx already just 1 year into our launch. Altogether with our partner, Bayer's efforts in Europe, we believe that the Attruby/Beyonttra franchise in 2026 will generate over $1 billion of revenue. Of course, all of this is possible given the unique biochemical and clinical characteristics of the molecule. As you all know in this room, it is the first and only near complete stabilizer as labeled by the FDA, and has provided what we call [ 3-42-50 ]. At 3 months, statistically significant separation from placebo, at 30 months, a 42% relative risk reduction against those same characteristics of all-cause mortality and cardiovascular hospitalization, and at 30 months, a whopping 50% reduction in hospitalization, suggesting we're able to help patients live longer and healthier lives out of the hospital setting. Over the course of the last 12 months, you've seen from us over 50 publications and abstracts delving into various aspects of this overall value proposition, as well as trying to better understand where our drug best performs for patient populations like the variant population, or patient populations like the AFib population. Today, I want to focus a little bit on one of the aspects that I think has been -- that has been underappreciated, which is the assets early separation from placebo. Some data that we published at HFSA, that I think honestly was missed by most investors and actually a lot of physicians, was that we had indeed observed a numeric separation in cumulative morbidity as early as 1 month with our drug. Now that's a bit of a head scratcher because obviously, if you think about the kinetics within the heart, it's probably not the impact of turning down of the amount of toxic monomer that's depositing in the heart that's actually driving this impact. And so we sort of scratch our heads and asked the question, what might be driving this? And it took us to analyzing some of the very unique hemodynamic and cardiorenal properties of this asset. And I won't spoil, nor do I have time to go through the whole story here, but you will see a series of publications over the next 12 months, suggesting that Attruby actually has renal protective attributes, analogous to the SGLT2 and ARB class, and totally unique to this compound. Now why might that be? Obviously, it is because Attruby is delivering the highest known kinetic and overall levels of stabilization in this space. I've said it before, and I'll say it again, Attruby simply sees more of the target TTR. It binds it more effectively with a superior KD2 binding as compared to tafamidis, and ultimately does a better job of gluing the tetramer together over time. For those of you that have been following the preclinical work in this space, you'll have seen the PNAS, or Proceedings of National Academy of Sciences paper that came out about a month ago, with some really beautiful mass spec work. And I'll read the conclusion from the authors just briefly. Our thermodynamic analysis further supports the notion that binding enthalpy, not affinity KD or change in goods to free energy, better predicts the confirmational stabilization imparted by these kinetic stabilizers. As many of you know, and as we published in [indiscernible], using an ITC approach, we have a vastly superior enthalpic binding mode as compared to tafamidis. Now the good news is we don't even need it because we also have a superior binding approach. And it wouldn't be a talk from me unless I trotted out a new quote from Jeff Kelly, as many of you know, the inventor of tafamidis, and the founder of FoldRx. This is an e-mail that he sent to our founders, Isabella and Mamoun some time ago, and he says, given the variability in soschiometry in the experiments between tafamidis and AG10, which is acoramidis, or Attruby, and TTR, the data will always tell the same story. That AG10 is better than tafamidis as would be expected from the determined binding constant. We wholeheartedly agree and we'll continue to interrogate the advantages of this ever better stabilization for the patients that we serve. Today, we're announcing something in tandem to those efforts. We've long sought the ability to pair upstream turning down of the toxic monomer that deposits in the heart because recall, both knockdowns and stabilizers are trying to turn off the faucet of toxic monomeric deposition in the heart with an agent that helps clear the already deposited plaque because, by and large, we are diagnosing patients too late, and at a point where there is already pathogenic deposition of amyloidotic plaque in their hearts. And the right way to do this is to establish a depleter or antibody-associated program that promotes the clearance of that already deposited plaque. We've been greatly privileged to be working with Dr. Richard Scheller, our Chairman of R&D, who, as many of you know, ran R&D at Genentech for a very long period of time, and was associated with Herceptin amongst many other great antibodies, and he's been leading this project for the last couple of years alongside our colleague, Christine Zhang. And what we wanted to do within this space was to build on prior efforts and really optimize an antibody against 4 key dimensions. First, obviously, we wanted to bind more target. We wanted to find, and in this case, a cryptic previously described but not employed binding site within the fibril to go after. Secondly, we wanted to clear more target by better recruiting macrophages to our antibodies upon binding. And then third and fourth, we wanted to improve antibody half-life by optimizing pH sensitivity within the endosome and then ultimately taking advantage of some of the novel literature on FcRn binding that many of you are familiar with to improve antibody half-life, therefore, making it more effective, and hopefully more convenient over time. And we are heartened to say that we've been able to create an antibody to date that actually checks off all those boxes, very close to development candidate, and we anticipate moving this program into the clinic in the coming 18 months. Okay. So I'd like to turn now from ATTR cardiomyopathy to our development franchise, and I'll start with our profound results that we published just a few months ago in the context of limb-girdle muscular dystrophy Type 2I. As a reminder, this is a deleterious condition with no available pharmacologic therapy that affects almost 7,000 patients between the United States and the EU. 2.5 months ago, we published the interim Phase III results from our trial that sought to look initially at biochemical impact against the causal biochemical damage associated with this condition. The bad news around this condition is that there are no available therapies. The good news is it's remarkably well described biochemically, owing uniformly to loss of function mutations in an enzyme called FKRP, which leads to a lack of glycosylation of what's called the alpha-dystroglycan complex in the muscle, and we sought to turn up that glycosylation level so that we could go forward and help patients. We powered the trial so that we could look at biochemical glycosylation of the ADG complex in tandem with a measure of muscle damage called CK. And sure enough, after 1 year, as we looked at the trial, we found a 1.8x increase, even more profound than we observed in Phase II in ADG glycosylation, and an 82% decrease concomitant in a measure of muscle damage called CK. So those were very heartening. But what we saw next, we didn't expect. We saw statistically significant improvements against measures of both ambulation and breathing. This is the first data set that looks like this as far as I know, in the muscular dystrophy space. And what was even more encouraging was for each of those two measures, both ambulation and breathing, we saw a decline in the placebo arm, and an incline or improvement in the therapeutic arm, suggesting that we are improving patients and in some cases, on breathing, and on ADG, returning a few patients back to normal within a year. That is a profound advance. When we talk about therapeutic cure in the context of what we do, we don't often think about small molecules. But this is truly therapeutic cure for a few of the patients that we have treated here. I want to elaborate on that data that we announced at top line with a bit more detail. These are data that we shared with the agency in mid-December, and these are the forest plots against all of the primary and key secondary endpoints that I just mentioned. And I don't have time to go through each single one of these plots, but I think you will see that the consistency of the plots, and the statistical robustness are encouraging. Furthermore, what you can see from this drug is treatment and effective treatment across a number of different subcategories, suggesting either early stage or late-stage disease. So for instance, for compound heterozygotes that tend to be more severe in this disease, we see marked efficacy consistent with what we see in the "milder condition", which is the L276I homozygous population. Additionally, we see consistent efficacy from young to old people who have had the disease for a long time, versus people who have just been diagnosed, and at different baselines of FVC. So beautifully consistent data that we were able to share with the agency. And perhaps the most important data pertains to the modified North Star test. As many of you know, this division of the FDA likes to look at North Star, or modified North Star, a very difficult endpoint against which to achieve statistical significance. We designed our trial to do so after almost 3 years. But after looking at the interim data 1 year in, what we showed was a 2.6 delta, again, with a decline in placebo and an improvement in what we saw on active with robust statistical significance. This was certainly -- our trial was certainly not powered to show this, and we were extremely encouraged to see this data, coupled with the data I just shared with you. We took all of that data into a presentation to the agency in mid-December, and they quote, we're very pleased that we had demonstrated consistent treatment effects on multiple efficacy endpoints and upon seeing the data, asked us to file our NDA toward traditional and full approval versus accelerated approval, knowing that leaving kids on placebo arm for the entirety of the design trial would likely be unethical. We anticipate filing this NDA sometime mid this year. I'll turn now to our efforts in ADH1. As many of you know, ADH1 is a condition that affects almost 12,000 Americans alone, making it one of the larger markets and certainly one of the more underdiagnosed conditions that we go after. Again, the good news here is that this condition is remarkably well described, owing uniformly to gain-of-function mutations in the calcium sensing receptor, and we are going after this condition having designed a negative allosteric modulator of the calcium sensing receptor. Again, just about a couple of months ago, we were privileged to announce our Phase III results in this category, where we demonstrated a 76% responder rate following encaleret treatment. Now response here is actually normalization of urine and serum calcium, which are the two things that drive all of the conditions in this disease. So low serum calcium levels is what drives tetany, brain fog and ultimately seizures and high urine calcium levels drive downstream nephrolithiasis, CKD, kidney stones and the like. Recall also that standard of care, which only had a 4% response in our clinical trial, is simply calcium supplementation. So even when patients can get back to normal levels of serum calcium, they're actually downstream harming themselves by loading up their kidneys with calcium. A 76% full normalization of patients once again applies to this concept that I talked about during my comments on LGMD2I. This is therapeutic cure for these patients. They are back to normal levels of calcium and could undergo and live a relatively normal life on a go-forward basis. Hearteningly, we also showed in 90-plus percent of patients response to the drug. So there's normalization and then there's response. 90-plus percent of patients were normalized as you look at their PTH, and they moved in the right directions when we thought about urine and serum calcium levels. So very few segment of this patient population would not be served with encaleret on a go-forward basis. So how do we find these patients? As I mentioned at the outset, this is a relatively underdiagnosed disease. How do we go about starting to find patients that would find this therapy useful? And the team has done a really nice job of providing really three angles to this. The first is to improve genetic testing and to partner with prevention, and other local providers so that we might offer a panel to identify pathogenic variants associated with the calcium sensing receptor. And as many of you know, we've also published some literature on what those variants are, and really drilled into the constellation of known pathogenic variants as opposed to the buses in this gene. Second, our commercial team created an ICD-10 code so that we might better codify and identify patients with frank ADH1 as opposed to chronic hypercalciuria throughout the course of time. And then finally, actually, the guidelines were updated to suggest genetic testing for those with nonsurgical hypercalciuria, so that they might see whether or not their ADH1 patients actually hiding within the context of that broader HP community. It's not unlike actually ATTR cardiomyopathy, or even hypertrophic cardiomyopathy, when I got started. These patients are hiding within the context of HFpEF, we needed to find them. Here again, we need to establish the algorithm to find the patients that would best benefit from this drug product. And extremely excitingly, what the results of these efforts have been to date is the identification of 1,700 unique patients based on, again, the efforts of these alone, plus the medical education that we've been doing. This underlies our projection there are about 3,000 to 5,000 identified patients associated with ADH1 today, but more importantly, in my mind, suggests that we have the right approach to continue to find new patients over time, especially after the therapy launches. This is pretty robust growth given the fact that the therapy is not even approved, or in the commercial marketplace today. Okay. Turning finally to an update on the encaleret program as it applies to an additional indication, chronic hypoparathyroidism. As you all know, for every medicine that we interrogate, our responsibility is to figure out all of the different ways it could be applicable to human health. In this case, the phenotype of restoration of urine and serum calcium suggested to us that this may be a useful and the first oral product in the context of CHP. And indeed, in a very small but robust in terms of its signal clinical trial in about 10 patients, what we showed was 80% normalization of urine and serum calcium in the context of chronic hyperparathyroidism. We took that data, coupled with the mechanism, coupled with what we've learned from our ADH1 trial to the FDA, and we aligned on an extremely exciting trial that we intend to prosecute starting midyear. We call it the RECLAIM-HP trial. What you can see from this trial design are really two salient characteristics. One, this is a 6-month trial. We intend to relatively quickly interrogate this compound to better understand whether or not as an oral agent, it can provide the types of efficacy we see with PTH replacement therapy or even better. Secondly, the primary endpoint, the proportion of participants achieving albumin-corrected blood and urine calcium within the target range. Now recall, our Phase II data, this suggests a very high probability of technical success associated with this clinical trial. So we are excited not only to launch an ADH1, but also to serve patients with chronic hypoparathyroidism on an ongoing basis. I'd like to turn now to our achondroplasia and hypochondroplasia franchise associated with our small molecule, infigratinib. As a reminder, this affects some 55,000 individuals between the U.S. and EU, and represents a significant unmet need. For those of you interested in this program, I would suggest that you listen in to the webinar that was recently published on Friday. Our colleagues, Justin To, Daniella Ragoff and Dr. Lager, we were very privileged to have her on the line, both talk about the architecture of this condition, as well as how meaningful infigratinib could potentially be to the folks we're trying to serve within this population. On that webinar, Justin mentioned that we have achieved last patient, last visit against our Phase III in achondroplasia and anticipate reading out that data to everyone sometime in Q1 of this year. Importantly, we also have first patient enrolled in our pediatric and toddler study. Recall, PROPEL 3 already is interrogating the broadest set of ages within the achondroplastic trial setting from 3 to 18, but we'd like to go all the way down to as low an age as possible, and therefore, PROPEL I&T is important. And then really excitingly, we have full enrollment completed for our Phase II portion of our hypochondroplasia study, again, a related condition arising from a different, but still activating mutation in FGFR3. As Justin mentioned during the webinar, and I think it's important to reinforce, this is the best and most advantaged approach within the context of achondroplasia. First, it is the only approach mechanistically to target this condition at its source, FGFR3 overactivation. Secondly, in the definitive animal model, it provides not only quantitative advantages as compared to the CMP class of medicines, but also qualitatively is able to deliver results against things like foramen magnum, surface area and things outside of long bone growth that ultimately are important to the community that we serve. Third, and most importantly, in the New England Journal of Medicine last year, we published quantitative outperformance of this agent in the context of achondroplasia, both when looking at change from baseline in AHV, as well as absolute AHV, and then coupling that with maybe perhaps the best endpoint given the variance associated with AHV, which is the Z-score where we showed a 0.36 plus standard deviation at month 12. The community was incredibly excited about these results in addition to the fact that we were able to the first -- for the first time to provide a statistically significant result against proportionality, a decrease of 0.12. We're the only agent in this space that's received breakthrough designation, suggesting that the FDA sees this as a marked leap against standard of care. And finally, and importantly, as we've done our market research, this is a convenient, safe and oral medicine, that allows all kidos that might want to try this agent to be able to try it in a convenient manner. And just so I can elaborate on that a little bit here. You can see a picture of the capsules on your left-hand side, again, 17 millimeters long, very easy to swallow. And if you have trouble swallowing that, you can break this up into the granules, which are 2 millimeters long and easily mixable with soft foods. Okay. So what does this look like in terms of the marketplace? We obviously have to start thinking about our commercial efforts. And for those of you that were here a couple of years ago, you'll remember that as we were getting set to launch in ATTR, we had done quite a bit of market research using a couple of different tools to better estimate what our share would be, and how to size our sales force. And I think actually, those projections have been fairly accurate. And we marry those now with a third tool that I'll talk about in a moment. So the first way that we try to understand how this agent might perform is by taking a variety of TPPs and using it in the context of market research, where we're able to go out to 80% of the physicians by volume that are prescribing today's currently available CMPs. The second is that we look at analogs and 3,500 molecules, many of them that are oral versus injections, et cetera. So we were able to look at the appropriate analogs to estimate what PKM market share might look like in this space. And then finally, in collaboration with MIT, Andrew Lowe and his QLS group, we have launched a Revenue Institute where we will be publishing on in the next few months, a brand-new algorithm that helps us better predict how our molecules will launch over time and indeed, how other molecules hopefully will launch in a future state. So I won't talk about all of the research here. You can expect to hear updates from us in the months to come, especially as we get a glimpse of our Phase III data. But here's the TPP that we actually tested in market research most robustly. And you can see, again, an indication that's the broadest indication in terms of age range being interrogated in our trial, an MOA that's a selective FGFR1/2/3 inhibitor, the dosing and administration that's a real mark step forward, a daily oral as opposed to a daily or a weekly injection. We put our delta in AHV change from baseline at the tippy top of what CMPs have been able to achieve 1.5 centimeters per year. And we put a well-tolerated AE profile into the TPP, which is effectively all of the safety that you've seen from this compound to date, less than 10% hyperphos, and importantly, avoidance of injection site reactions, hypotension because recall, that's really where the CMP category comes from and the excessive hairiness that has been otherwise observed with some of the CMP products. And what we found based on that TPP was a stubbornly consistent 52% market share. We believe that we will take a vast majority of this market, but we will at least, given the market research, take a majority of the market given the profile shown on the left. So again, we anticipate data so we can fill this in for real and go and take somewhere between a majority and vast majority of the market based on data to come. Last but certainly not least, are our efforts in Canavan disease. As many of you know, Canavan is an extraordinarily rare, extremely deleterious neurodevelopmental disease, and we've been taking a gene therapy approach to see what we can do to serve children affected with this condition. I don't have time to walk through many slides on this, but what I will show you in this single slide associated with Canavan is the evolution of the data that I presented last year, where you can see at our eve of 14 high dose, robust and profound decreases in the causal biomarker associated with this disease, which is urine NAA and mirrored by CSF NAA. And very hearteningly, you see a dose-responsive improvement in the behavior of these children, improvements such as sitting, head control, reaching and grasping and in certain cases, ambulation where you would certainly not expect to see it. We continue to dose children and assess the safety and efficacy of this product, and we anticipate filing its BLA sometime in 2027. Okay. So hopefully, three launches upcoming. How are we going to do it? That's a lot for a small biotech, and we think we can employ this decentralized model that we have to continue to scale launches, those three launches, hopefully, if we're lucky with the achondroplasia top line, and hopefully launches to come with some of these additional indications that I talked about. And what we've done here is we've preserved the affiliate structure so that we have the teams that are close to the physicians in any given therapeutic area, that are close to the patient and patient advocacy groups, and that are close to the data, really running the launches, but they're doing so in partnership with the wonderful team that Matt Outten and our commercial colleagues have put together, therefore, making it such that we don't have to respend the money to set up the infrastructure. As many of you know, in rare disease, the preponderance of spend is not against FTEs or the field force every time, but rather against the back end of market access, patient services, analytics, et cetera. So we can use that already established expertise and apply it to launch after launch in tandem with the affiliates. And so that's what we intend to do over these next 3 launches and hopefully, maybe 5 launches associated with the comments I've made to date. But the question is where else do we want to take this platform in the years to come? And that takes me to the final points maybe I'll make on why we believe it is still day 1 in this area of genetic disease. And I won't belabor it because I think many of you in the room know this. But about 3 years ago, I was up here chatting with Anup about this concept of missing heritability. And why is it that so much of what we see in terms of phenotype is not well captured by genetic information. And it turns out, as many of you know, who have been following the literature that just an increase in whole genome sequences versus exome sequences, coupled with the higher density of data has allowed us to really fill in the gaps around missing heritability, and to begin to really tamp that down. But maybe most excitingly, we're able to start to identify these new variants and then connect them with mechanism, and then connect that mechanism with phenotype. What's allowing us to do that? Obviously, advances in long-read sequencing, allowing us to identify things like structural variants. Obviously, advances in things like having a pan-genome, a better reference against which we can understand variants, the pre and aforementioned increase in data density associated with these databases like UK Biobank and the like. And then really importantly, the ability to interrogate the function of these variants in cell and tissue-specific experiments so that we can tease out their function and better design therapeutics that target well-described conditions at their source. A fingerprint of all of these advances is simply the pipeline that we see at GondolaBio, a company, as you know, that is a sister company to BridgeBio, and a company that you collectively own as investors in BridgeBio. Here, you can see 17 different programs in a span of just a year, all pretty early stage, advancing all the way from early-stage research to Phase II, but in important areas of high unmet need. Investors will be familiar with areas like EPP, ADPKD, alpha-1 antitrypsin, CMT1A, neurofibromatosis type 1 and the like. I don't have time to go through all of these programs, obviously, but I'd like to touch on one example of, again, the well-described process that we put forward at BridgeBio, which is to take generally small molecules and target these well-described conditions at their source. So I want to talk a little bit about our EPP program. Most of you in the room, I think, and on the line are familiar with EPP, but for those of you that are not, it is unfortunately a very large unmet need, affecting some 20,000 to 25,000 people between the United States and the EU. So that makes it one of the larger disease states that we work on. And when it does affect people, unfortunately, it affects them with deleterious morbidity associated with skin damage and excruciating pain, as well as downstream liver disease. That's the bad news. The good news is that the path of mechanism of this condition has been very well described over the years. So what we can see here from the cartoon on the left-hand side of this slide is that this condition uniformly arises from mutations in the heme synthesis pathway, most commonly through mutations in ferrochelatase. And what that does is it promotes the production of a compound called PP IX, which then is present in the plasma, the skin and the bile at too high a concentration. And because PP IX is photosensitive, it drives the phototoxicity and pain that I just mentioned. Now there are many different ways to go after this condition. There are noncausal ways to go after it like using canning agents that has been the approach of Clinuvel, Mitsubishi Tanabe. And then there are different ways to target this causal pathway. Certainly, this medicines has one where they try to inhibit the intake of glycine. And we looked at that product, and we started to ask ourselves, how do we improve upon it? The intake of glycine and its inhibition takes a very long time to provide PP IX reduction. It's not able to provide PP IX reduction to the marked levels that would be required to take people back down to, let's say, "a normal range of PP IX". And you can't do it safely. As you know, GlyT1 inhibition, which is associated with glycine intake comes from the schizophrenia field and is associated in EPP trials alone with high levels, almost 50% of dizziness and other AEs. So we asked ourselves, how else might we target this [indiscernible] at its source, but do so avoiding some of those handicaps? And what we decided on, in collaboration with Dr. Ma at University of Pittsburgh, was to inhibit the egress of PP IX from the red blood cell by inhibiting potently its solitary transporter, which is entitled ABCG2. And so we have designed a compound by the name of PORT-77, which is an orally bioavailable, highly potent inhibitor of ABCG2 that in cellular models, animal models and the like has provided best-in-class efficacy and a beautifully safe profile that allows us to turn down levels of PP IX in the plasma and importantly and uniquely, PP IX levels in the bile, saving off both the phototoxicity and pain that patients suffer from, but also the downstream liver disease. So I'll just go right to the point here, which are the results of our Phase IIa trial, which we recently just generated about a month ago. And here, you can see the design of our GATEWAY trial effectively to interrogate 2 different doses of PORT-77, and to look at the change in plasma PP IX as compared to baseline and running placebo. We also obviously wanted to interrogate PK, safety and tolerability. So what did we find? Firstly, and hearteningly, we found a profound impact in terms of the diminishment of PP IX in the plasma. This has not been seen before, 75% reduction in PP IX levels. And even more importantly, because every minute matters for the patients that we serve, we were able to take action in a matter of hours as opposed to weeks from this medicine's drug. And within days, we reached steady state at 75% reduction. So the marked efficacy associated with this compound is unique in this space. But perhaps even more encouraging to me was the next slide. I have sat on many clinical trials, and I rarely get this level of consistency from a Phase IIa. Here, you can see all 12 patients, and I'll just take your eye to the dark blue lines here. Every single patient dosed with a high dose PORT-77 experienced a reduction in PP IX levels. Maybe the smallest reduction observed was 57%. And again, the mean was 75%. So not only do we see profound reductions in PP IX levels, not only do we see relatively quick reductions in PP IX levels, we see very consistent action from this drug across the patient population. And importantly, we are doing it safely. You can see a numeric imbalance in actually favor of the treatment as compared to placebo in most of these rows. This is importantly different than the other molecules in this space. Okay. So what I hope I've convinced you of in a few brief slides, and we will certainly be elaborating on this more in talks to come is that we have an ABCG2 inhibitor that it applied in its application to EPP allows for potential best-in-class PP IX reduction. It has a dual mechanism that targets all aspects of the condition, has a clean safety profile, and that we're able to see it and that reduction within hours, not days to weeks. This is just one snapshot of all of the progress that you as investors own across the ecosystem of BridgeBio. We've got BridgeBio and its late-stage franchises. We certainly have early-stage research ongoing, as I highlighted with the depleter program, and there are other programs in that same vein at Bridge. We have all of what's happening at GondolaBio. And indeed, you are substantial owners of BridgeBio Oncology Therapeutics, where the CEO of that effort, Eli Wallace, will be talking a bit later today about some of the exciting updates against its franchises as well. So lots going on, lots to do for the patients that we serve. And this is just a summary of all of the issues that I've covered today. Commercial momentum, late-stage development momentum, early-stage research and development momentum, all portending, I hope, in partnership with you all in this room, the ability to serve many more patients in the years to come. And it wouldn't be a JPM slide if I didn't end on the comment that we are well financed to undertake all of these activities in the coming years, and that all collectively, these activities will create a steady drumbeat -- hopefully, drumbeat, hopefully, of advances for both the patients that we serve and investors in and around the stock. And so with that, I will thank you all for your attention. And if we have time, I'll take a question or two.

Neil, your presentation was so robust. I do not have any questions.

Thank you Anup.