BridgeBio Pharma, Inc. — Call Transcript 2025

Ladies and gentlemen, thank you for standing by. My name is Krista, and I will be your conference operator today. At this time, I would like to welcome everyone to the BridgeBio Pharma, Limb-girdle Muscular Dystrophy Type 2I/R9 FORTIFY phase three interim analysis results webinar. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question at that time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press 1. Thank you. I would now like to turn the conference over to Dr. Neil Kumar, Chief Executive Officer. Dr. Kumar, please go ahead. Thanks, everyone, for joining this call. Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with Limb-girdle Muscular Dystrophy Type 2I/R9. The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current and future patients struggling with this condition. Before I set the corporate context for this readout, I want to begin with the most important slide in this document, slide four, a thank you to the amazing and inspiring patients and families, advocates, physicians, clinical research staff, and collaborating research partners that made this study possible. As we have hopefully demonstrated in the past, across conditions as desperate and disparate as MOCD type A and ATTR cardiomyopathy, we recognize now our responsibility to the community that made this work possible and therefore plan to move expeditiously to provide this medicine to patients broadly. Turning to slide five, I'll take a brief moment to provide some corporate context for today's data. As many of you know, BridgeBio Pharma was founded almost 10 years ago to target well-described genetic diseases at their source. Our efficient R&D engine has helped generate almost 20 INDs and three approvals to date, and we hope to add BBP-418 to that list in short order. Today's data represent the first of three major current and upcoming phase three readouts for us, with results from our ADH1 and achondroplasia efforts expected in the near term as well. Together, these and ongoing earlier stage programs should provide, on a risk-adjusted basis, a reasonable tapestry of impact for the patients we serve and investors alike. Turning back to the program of the moment on slide six, I thought I'd make two final observations that pertain more broadly to our efforts. First, although we deploy many different modalities in an effort to target causal drivers of Mendelian disease, where we can, we often use small molecules. In many of the disease areas in which we play, there's sometimes a misconception that small molecules, while perhaps being more efficient to develop or safer, can't provide the type of efficacy other modalities can. Here, with perhaps the most impressive data set generated to date in the muscular dystrophy space, we once again show that the quantitative impact on the causal genetic driver is what counts, and that small molecules can provide optimal impact safely and obviously in the most cost-efficient form for society in the long run. Secondly, we were profoundly enthused to observe improvement for the patients in this trial. It's not a new concept, but a good reminder that intervening to take away the biochemical insult can result not only in the halting of ongoing pathology, but indeed in improvement. Reliably improving patient lives is the ultimate aim for any therapeutic we develop, and BBP-418 has met that high bar. With that, I'll turn it over to Christine and team to tell you more about the specifics of this remarkable trial result and the next steps for this program. Thanks, Neil. First, I'd like to thank our BridgeBio Pharma team who have worked at a high pace with high standards to achieve this milestone. I'd also like to thank the community of collaborators, patients, caregivers, investigators. Without them, this would not be possible. When I speak with patients, I'm first inspired by their courage and struck by their hope for a therapy. Because LGMD2I/R9 is a progressive disease, what they can believe in is something that could stop or slow the progressive loss of daily function. These data show BBP-418 could be transformative in not only slowing the loss, but improving clinical function too. On slide nine, the data are striking in how consistent and how robust it is across all key endpoints measured. The results were highly statistically significant for glycosylated alpha-dystroglycan at three months, at 12 months, serum creatine kinase at 12 months, and our functional measures, 100 m time test, and forced vital capacity at 12 months. On the next slide, we compare these results to our expectations. Relative to our base case, this was really a home run scenario. We expected robust biomarker changes in glycosylated alpha-dystroglycan and serum creatine kinase, which were demonstrated and exceeded our expectations. We did not expect statistical significance, however, on the functional endpoints. The study wasn't powered for statistical significance on functional endpoints, so the fact that we saw such high statistical significance on 100 m time test and forced vital capacity at 12 months is really quite remarkable. Not only did we see separation from placebo, we saw improvement in the treatment arm. This is remarkable and the first time that I'm really aware of any therapy demonstrating functional improvement in a randomized controlled study in limb girdle. This underscores the potential for BBP-418 first to market for a disease-modifying therapy for LGMD2I/R9. I will now turn it over to our Chief Medical Officer, Dr. Doug Sproul, to walk through the data. Thank you, Christine, for that kind introduction. It is a distinct pleasure of mine to have the opportunity to present the top-line phase three FORTIFY interim analysis data. It is a special privilege as a member of this community to be able to present such impressive data. Before I present the data, I would be remiss without expressing the immense appreciation that we have for the patients and their families who have contributed and sacrificed so much to advance care and research in LGMD2I/R9. Particularly call out the tireless work of our patient advocate community partners and the many physicians, clinical trialists, caregivers, clinical research staff, and other collaborating research partners who have all contributed in such a major way to this data and the ongoing advances that we see in the field. Moving to slide 13, FORTIFY is our ongoing randomized placebo-controlled phase three study of BBP-418 versus placebo. This is a well-controlled and balanced study comparing patients treated with BBP-418 versus placebo in a double-blind randomized controlled manner. Patients are randomized two to one to receive BBP-418 versus placebo. We are reporting the top-line results of our interim analysis that involved the first 72 patients to complete at least one year of clinical study. I'll be discussing our interim endpoints that we have assessed in a formal, statistically rigorous manner. That is including our biomarker glycosylated alpha-dystroglycan, the change from baseline at three months as well as at 12 months. We are also assessing creatine kinase, which is a widely used and well-established marker of muscle injury and breakdown. We are assessing two important and clinically meaningful clinical measures widely used in neuromuscular research. The first is the 100-meter time test, which is an assessment of ambulatory function as well as fatigue. The second is a broadly used measure of pulmonary function, forced vital capacity. As I've mentioned, this is a double-blind randomized control trial. The placebo and BBP-418 arms were stratified by age, by ambulatory status, as well as by genotype to allow a well-balanced and well-controlled study that I am eager and proud to present today. Before I get into the clinical markers, I wanted to give my colleague Uma Sinha the opportunity to discuss the dramatic results from our alpha-dystroglycan glycosylation bioassay. With that, I'll pass the baton to her to speak. Thank you, Doug. It's an incredible pleasure and a source of pride to be able to present the biomarker data that the whole team has worked long and hard on. Most importantly, the patient samples, which allowed us to develop the biomarker assay. I'm incredibly grateful for those. First, let me remind everybody about the mechanisms of this disease. LGMD2I/R9 is caused by mutations in FKRP that lead to decreased enzymatic activity of FKRP. This in turn reduces the extent of glycosylation of alpha-DG. Hypoglycosylation of alpha-DG is a core defect in the disease, and this is consistent with the genotype-phenotype association of L276I mutant and other heterozygous FKRP genotypes that are in the literature, and we have also tested in our natural history study. The hypothesis that we are testing here is that by BBP-418 dosing, we are targeting the disease at its source, restoring glycosylation of alpha-dystroglycan, and thereby enabling the muscle to continue binding laminin at the expected level. We have developed a proprietary validated western blot assay to accurately and reliably measure glycosylated alpha-DG directly in skeletal muscle tissue. This is important on multiple levels. It's a proprietary assay. FDA has reviewed our approach and agreed that it is reasonable. What's novel about this assay? The assay uses two antibodies for immune detection of alpha-DG. One directly measures glycosylated alpha-DG, and the other measures the core protein. It's important to remember that the first antibody is detecting the functional moiety, the moiety responsible for laminin binding. In this slide, we're showing you representative data from phase two. Both glycosylated and non-glycosylated protein is being shown here. As you can see in the untreated patients, there's barely a signal for the glycosylated alpha-DG protein component. In this data, we have confirmed that upon BBP-418 dosing, already at three months, we are detecting an increase in the glycosylated alpha-DG level, which is sustained at the six-month level. This was the dose-finding phase two data, so it allowed us to build on our hypothesis. Another thing that we have done is use this validated assay to measure baseline levels of glycosylated alpha-DG across our natural history, phase two, and phase three studies. I'm happy to report that the results have been consistent and given us more faith in what the assay is measuring. As Doug has already mentioned, the change from baseline in glycosylated alpha-dystroglycan was the primary endpoint of the phase three trial. We have observed a robust and rapid increase in glycosylated alpha-dystroglycan at three months. I'd like to focus on the three salient points that this data set is telling us. One is that the change from baseline in alpha-dystroglycan is robust and seen rapidly at the three-month time point, very statistically significant. This increase is sustained through the 12-month period. The third point I'd like to remind everybody about is that our knowledge in the natural history study as to how the baseline levels of glycosylated alpha-dystroglycan behave, that has been confirmed in this study. There was essentially no change in the placebo arm. Our preclinical data in mouse models, as well as in the natural history study, told us that targeting a 5% change in glycosylated alpha-dystroglycan would be expected to be a clinically meaningful benefit in the patient population. As you can see from this data, we saw an increase of 17% of control at the three-month time point, and the effect was sustained at the 12-month time point with a 23% change from baseline. Target was 5%, so we have definitely exceeded expectations here. I'd like to now turn this over to Doug to delve deeper into the clinical data. Thank you, Uma, for that fantastic overview of the glycosylated alpha-dystroglycan bioassay. I'd like to build upon those amazing and dramatic results that we're seeing from our bioassay, which shows an approximate doubling in glycosylated alpha-dystroglycan levels amongst patients treated with BBP-418. We're seeing a similarly dramatic, large, statistically significant reduction in serum creatine kinase amongst patients treated with BBP-418, a difference of 82%, a decrease of 82% from baseline at 12 months. This is an amazing observation, just to put it in a little bit of context, a large proportion of patients treated with BBP-418 achieve levels that are within one or two times the upper limit of normal. This suggests a marked reduction in muscle breakdown that's indicated by this reduction in serum creatine kinase. We demonstrated with the bioassay that we have an impact on cellular physiology, that we're improving and increasing glycosylated alpha-dystroglycan levels. That's translating to a large and important reduction in muscle breakdown that's measured using and demonstrated using serum creatine kinase. These are results that we expected to see, to be perfectly frank. We have confidence in this compound. What is most exciting is what I'm going to talk about in the next few slides, that this physiologic effect, this biologic effect that we're able to demonstrate now, excitingly translates as well to signs and signals of meaningful and important clinical impact. We are excited to present data that is demonstrating that third link in the chain, that we're demonstrating the impact on the physiology that's translating to reduced muscle breakdown. Now we're able to report, excitingly, an impact on clinical function as well. We are observing a 0.27 m/s improvement amongst patients treated with BBP-418 versus placebo in the 100 m time test. To put a little bit of clinical context, the 100 m time test is a broadly used clinical and clinical research tool to assess ambulatory function and fatigue in patients with neuromuscular diseases. As we have seen in the natural history of the disease and demonstrated in our placebo arm, we see a consistent and inexorable decline in performance on this scale. We see a 0.12 m/s decline in patients treated with placebo. In contrast, we're seeing an improvement in patients treated with BBP-418 in their velocity of performance on the 100 m time test. This translates to an approximately 14 s faster performance amongst patients treated with BBP-418 when compared with patients treated with placebo as far as the time to complete this test. This is a statistically significant result, and it's a clinically meaningful result that we're seeing in patients treated with BBP-418 on their ambulatory function. Moving to the next slide, we're seeing a similarly dramatic and remarkable and improving performance in pulmonary function in patients treated with BBP-418 versus placebo as well. Amongst patients treated with BBP-418, we see a 3% increase in percent predicted volume from baseline, which represents an approximately 5% increase in percent predicted volume versus placebo. Taking a step back, pulmonary function is a critical system impacted in patients with LGMD2I, has a marked impact on morbidity and mortality. Forced vital capacity is measured in liters, but then adjusted for the gender, height, weight, age of a patient to give a percentage of how they should perform on this test. What we know from the natural history is that we see an inexorable 2% decline and loss year upon year upon year upon year, and that's actually seen in our placebo arm as well. In contrast, patients treated with BBP-418 have experienced an improvement in pulmonary function, an improvement in forced vital capacity that represents a 5% difference between the percentage predicted volume in one year between patients treated with placebo versus patients treated with BBP-418. This is a broadly clinically meaningful as well as statistically significant result that we're observing in patients treated with BBP-418 in this study. This summarizes, and not to beat a dead horse, but frankly to beat a dead horse, we're seeing not just stability, we're seeing not just a slowing of the reduction in loss compared with placebo, but we're seeing an absolute and statistically significant and clinically meaningful improvement in patients treated with BBP-418, not just with placebo, but also with their baseline status. That's a remarkable and really unprecedented result, particularly in the context of a double-blind randomized clinical trial. This is the most impressive placebo-controlled data, in my opinion, in the LGMD space by a wide margin, perhaps in the entire muscle disease community to this date. I'm extraordinarily proud and excited to have had the opportunity to present this data to you today. I'm equally proud and happy to report that we have a continued highly favorable safety profile of BBP-418. We have no new or unexpected safety findings that have been observed in our phase three study. These are results that are consistent with our phase two study, consistent with everything that we previously reported. We have a low discontinuation rate overall. It's higher in the placebo group. We have no treatment-related serious TEAEs that have been observed in our phase three study. The interim analysis continues to support that favorable risk profile as well as what I would consider a much increased benefit profile of the product. We're excited to present these top-line results today. What we've executed on to date sets the stage for an ambitious year and years ahead for our program, and we're extremely excited to move this program forward aggressively into the commercial phase of development. We plan to engage the FDA to discuss our pathway for NDA submission later this year or in early 2026. We intend to present the broader phase three data from our FORTIFY interim analysis results at the Muscular Dystrophy Association Clinical and Scientific Conference in March of 2026. We furthermore intend to file an NDA with the FDA in the first half of 2026 and anticipate a US approval and commercial launch of BBP-418 to treat patients with LGMD2I/R9, potentially in late 2026 or early 2027. With that, I would like to introduce my colleague Matthew Outten, our Chief Commercial Officer, who will present our overall commercial strategy. We are very excited about the data discussed today, which set the stage for BridgeBio Pharma's next commercial launch. Over the past 18 months, we've been preparing for this moment, building on the successful launch of Attruby to establish a robust commercial foundation across all functions, including market access, operations, analytics, and marketing. We will now leverage this infrastructure to launch BBP-418, supported by a dedicated field sales team that we have been proactively planning in anticipation of today's results. Our proven launch playbook will enable rapid mobilization for a launch that positions BBP-418 as the standard of care in LGMD2I/R9. We will continue to drive education and awareness as we move toward approval. It's important to remember that today represents the first and only positive data in LGMD2I/R9, a major milestone on our path to approval and for the community that we serve. We look forward to sharing more about our commercial strategy as we get closer to approval. For today, there are two key takeaways. First, the data are as strong as we could hope for heading into launch. Second, our commercial organization is ready to execute, drawing on the same experienced teams that successfully brought Atrubi to the market. We are poised to do it again with BBP-418. With that, we will now open the discussion and start the Q&A portion of the call. Thank you. We will now begin the question and answer. Thanks, everyone, for joining this call. Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with limb girdle muscular dystrophy type 2I/R9. The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current. If you would like to ask a question, please press 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, again, press star one. We also ask that you limit yourself to one question. Your first question comes from Tyler Van Buren with TD Cowen. Please go ahead. Great. Good morning, guys. Congratulations on the tremendous results. It looks like the results exceeded your home run scenario for the interim. I'm curious just to better understand what you think explains the outperformance. The 5% FVC benefit seems striking. Could you elaborate on the clinical significance of that 5% as well as the 14 s improvement on the functional outcomes? Why would the FDA allow patients to continue on placebo for another two years given these data? All right. Thanks, Tyler. I don't think that was one question, but we'd love to answer all of them. I'm going to turn it over to our team advisor. Hi, this is Doug Sproul. I'll address the first question, which was regarding why we saw the results that we did and whether we were surprised by the results. I have personal belief in this compound. Personally, this was my hope and expect hope that we would see this. I believe that this product would have demonstrated this at any point. My biggest concern, frankly, was the endpoints and the ability to demonstrate a material effect over a relatively brief period of time. There are two aspects, I think, that drive how we were approaching the study and explain the outside results. The first is that our study was structured around the concept of stability. It's been reiterated over and over again from the community that just stabilizing the disease, stopping it from getting worse, was an important advance that they would consider a strong win. Our program was based around that as being kind of the minimal efficacy that would be clinically and important for patients and really a meaningful advance for the field. We also expected and always concern ourselves with the concept of a placebo effect. Anytime you do a study in a placebo-controlled manner, patients perform differently than they might in an otherwise open natural history perspective. Those two aspects were brought into account as we designed and structured this study. While this is an upside scenario, it's something that we hope to be able to demonstrate. It wasn't what we considered necessary. This is gravy on top of the turkey, so to speak. I think that explains why we're seeing it. There's such a much greater difference in placebo versus the clinical improvement that we're seeing on these measures, and that would drive the statistics. I think the second question was regarding the meaningfulness of these measures, particularly FVC. FVC, forced vital capacity, is a broad tool used in clinical practice across multiple specialties. FVC has been used as an endpoint in a number of different trials, both intrinsic pulmonary diseases as well as in the neuromuscular community. Depending on the different studies, there are different approaches for what would define clinical meaningfulness in a specific disease. The difference we're seeing at 5% is broadly within and above the ranges that people generally consider as intrinsically meaningful in clinical trials and in clinical practice for this disease, and in clinical practice in general use in specific for this disease. The third question, I can't remember. The third question was about the ability to continue treating people in the study and the placebo arm. I think on that question, Tyler, I think it's a good question. Obviously, with the strength of this data and the clean safety profile, it's something that we're going to have to align with the FDA on before we can make any, you know, on the optimal path forward before we make any changes. Your next question comes from the line of Salim Syed with Mizuho. Please go ahead. Hey, congrats, guys. Thanks for the question. If you don't mind, I'll also ask three questions. I guess the first one here is just on the different subgroups you guys had in this trial, the L276I homozygous patients versus the other FKRP genotypes. Can you maybe just articulate if there was any difference between the two groups, or if you saw more or less benefit in one versus the other? Then just a clarification just on the N that was in the different clinical endpoints here. I think you had like 49 on one, 46. This is all for the drug arm, 40 for like 100 m time test, 35 on forced vital capacity. Can you maybe just clarify why the different N on the different clinical measures at 12 months? Lastly, if you think this mechanism could be used in other LGMD subtypes. Thanks. Okay. Thanks, Salim. Uma, you want to take the first part of that question? Sure. As you could see when Doug showed the study design, we had a very broad enrollment criteria for the phase three trial. It included both the homozygous L276I patients, and that's about 75% of the study population representing what we see in real-world evidence. The other 25% were the heterozygous and the other FKRP genotypes. We have seen very robust and highly statistically significant results in both of these genotype segments. This is quite consistent with BBP-418 to be a disease-modifying therapy, an oral disease-modifying therapy with a potentially very broad inclusive label. As you can tell, this data is very new to us, so we're analyzing all subgroups and getting clarity on what the data means. Again, very, very promising, highly statistically significant data. Additional details as they emerge, we're going to be presenting it in future medical meetings. I'll turn it over to Doug to answer the question. The second question was why do we see different Ns on some of the different endpoints? The quick answer for that is that the data incorporates the available data. In the case of the 100 m time test, there are some individuals who are unable to perform the test and are therefore not incorporated into the analysis. For forced vital capacity, our collaborators applied a rigorous standard to ensure validity of the test and the assessments. There were certain patients who were excluded based on their inability to perform the test correctly. This is incorporated into the test statistic, and the test statistic that we are reporting is a conservative adjustment to reflect that. Yeah. The other part about it, Salim, is just the enrollment rate. For example, the primary endpoint of glycosylated alpha-dystroglycan at three months looks at all the patients available at three months, but then, of course, not all of them made it to the 12-month time point at the same time to collect those data. I think your last question was about the applicability of 418 in other LGMDs. We do believe that it could be applicable for LGMD2M and 2U in the US and Europe. These are a little bit smaller conditions than 2I. In Japan, it may have potential in Tokiyama. That's a muscular dystrophy that is actually kind of a found mutation in Japan. It's specific to Japan, but actually the second most common form of muscular dystrophy in Japan. Those are probably the most likely mutation expansion opportunities for 418 specifically. Your next question comes from the line of Corey Kasimov with Evercore ISI. Please go ahead. Hey, good morning, guys. Thank you for taking my question and great to see such strong data. I wanted to ask more about the commercial opportunity. I'm curious, at this point, what percentage of patients are diagnosed today, both in if you can split it between like in the US and globally? From a strategic standpoint, do you plan to commercialize 418 yourself outside of the US, or would you look to out-license the molecule? Thank you. Thanks. I'm going to turn it over to Matt. Hi, Corey. Thanks for the question. First, we plan to launch ourselves globally, and we've been preparing in anticipation of positive data. Those assumptions that we put into that include about 7,000 patients between the U.S. and Europe, and about 2,000-2,500 of those are in the U.S. Just to give a little bit of color on some of the commercial parameters that we're looking at, we'll start to refine our pricing assumptions, things like that. As you're thinking about what to expect, I would expect sort of normal rare disease pricing similar to other recent rare disease launches. We'll be using the current infrastructure that we have to kind of put all this together. It should be another blockbuster drug for BridgeBio Pharma. Yeah. I think I would add just on the diagnosis rates, it's a little TBD right now since there's nothing available for these patients right now. There's no therapies. We must be the first to market for, you know, disease-modifying therapy. I will say I think there's some tailwinds already that exist in the market. There is sponsored genetic testing that's available, for example. I guess, you know, anecdotally, our experience with the clinical trial enrollment may suggest that there's actually kind of maybe more patients identified than we thought. I mean, with the clinical trial enrollment, we enrolled it eight months faster than expected and 20% more patients than expected. The demand for treatment and to be in a study there, again, suggests that there might already be a large volume of patients identified. Your next question comes from the line of Mani Foroohar with Leerink Partners. Please go ahead. Hey, guys. I'd like to add my congratulations on the data. I have a quick question about correlation between glycosylated alpha-dystroglycan and the various functional measures. Can you share with us to what extent we could get a little bit of a sense of the correlation between one and the other, recognizing you're limited to what you've already disclosed? Where might we look to see a more sort of detailed disclosure of how the one correlates with the other? Yeah. Thanks, Manny. That is going to be part of the ongoing analysis. This is really only that top-line data. We're going to use that data to have a discussion with the FDA, and we'll present a fuller data package most likely at the NDA in March. Your next question comes from the line of Josh Schimmer with Cantor. Please go ahead. Hey, congrats on the data, and thanks for taking the questions. Maybe just clarifying for the U.S. patient population, you'd said 2,000-2,500 patients. Are those all identified? How did you kind of come up with that estimate, especially because you suggested it potentially could be higher? Thank you. Right. The question was about just how we came up with our patient number estimates. I think that's the question. The estimates are derived from basically the prevalence in the Northern European population. This is a disease that has a founding mutation in Northern Europeans, so the prevalence is much higher in Northern European countries and places where Northern Europeans immigrated to. If you take those prevalence rates and extrapolate them out to the broader population, that's what we've come up with for our patient population. Your next question comes from the line of Biren Amin with Piper Sandler. Please go ahead. Yeah. Hi, guys. Thanks for taking my questions and congrats on the data. I guess, you know, given the strength of the results on the clinical functional endpoint, and you talk about NDA filing in first half 2026, do you still plan to pursue the accelerated approval pathway, or is there a path to full approval? Maybe second question on, you know, a path for ex-US approval. Would you pursue approval prior to readout of the full analysis? I guess, you know, third question is, when can we expect the final full analysis from the trial? Yeah. Thanks for the question. I think it's a good question. Obviously, given the strength of the data, the improvement on the functional endpoints, and the clean safety profile, it is the key question that we want to align with on the FDA about whether to seek an accelerated approval, which is our original strategy, or if this data, as we think, supports a full approval in the U.S. In Europe, we are also going to align with the European regulatory agencies on a path forward there. I think the key principle for us is, given the strength of this data, how do we accelerate access for patients as quickly as possible? Your next question comes from the line of Andrew Tsai with Jefferies. Please go ahead. Hey, good morning. Thanks for taking my question. Congrats also on the compelling data set. Aside from the FDA meeting that you have, what gating items, if there are any, are still outstanding before you can file the NDA? Do you need to run any other peripheral studies in the meantime, or do you even have enough drug for a commercial launch? Secondly, does it make sense to file for breakthrough designation? Thank you. Yeah. The gating item really is this alignment with the FDA on whether we're seeking accelerated approval or whether we're seeking traditional approval. You know, we don't anticipate that that's going to affect our timelines. We still anticipate filing our NDA in the first half of next year. We already have priority review. We also have the rare pediatric designation on this program as well. At this point, I don't think that filing for breakthrough is going to give us any additional benefit. Your next question comes from the line of Danielle Brill with Truist. Please go ahead. Hi, guys. Good morning. Thanks so much for the question and congrats on the excellent data. I have a few questions. First, I'm just curious, maybe you can walk us through how you selected the 100-meter time test and forced vital capacity as the functional endpoint measures for the 12-month analysis. Is there something specific about these that would make them more sensitive to a change after 12 months than, say, NSAID or a 10 m walk test? Were the changes observed in the placebo arm on 100 m time test and serum creatine kinase levels also consistent with natural history? Maybe just a clarification. In your prior conversations with the agency, were they generally supportive of a potential full approval filing with 12 month data that showed significant improvements on functional benefits? Thank you. Thanks for the question. Doug, do you want to take the clinical question? I'll take the clinical questions, and then I'll kick it back to Christine for the regulatory question. The first question is why those endpoints and how is that different from the other potential endpoints that you might excel? We selected specifically the 100 m time test and FVC because of the expectation that these were two endpoints that would be likely to be able to show relatively early association and improvement with following administration of the therapy. The 100 m time test is the, I would call it the modern version of the six-minute walk test, the measure of ambulatory function and fatigue that is highly sensitive to changes in function and ability that shows a better ability to differentiate decline in higher functioning patients than the 10 m walk test. We felt that this is a more sensitive scale than the other ambulatory measure. FVC has been well established by the history of the disease to show pretty outsized decline. The 2% decline that we see in the placebo arm mirrors what we see in the published natural histories, and that's a pretty stark year-upon-year-upon-year decline. This was specifically chosen because of the decline that we expected to see in the untreated patient. What we're demonstrating today, though, is not just an avoidance of that decline, but a pretty marked improvement in the overall function in those two measures. With regard to the regulatory question. Yeah. I'll take the regulatory question. Maybe just to back up, the way we designed the study was really in alignment with the FDA, which is the primary endpoint was the North Star endpoint at 36 months. That was the endpoint that the FDA strongly encouraged us to use for approval. Given that, you know, that incident is a relatively insensitive one, takes a long time to show treatment benefit, that's why we wound up with the study with the interim analysis at 12 months where the primary endpoint was based on glycosylated alpha-dystroglycan. The strategy was to seek accelerated approval based on the biomarkers, based on the fact that they are the cause of this disease, and we're targeting the disease at its source and directly impacting glycosylated alpha-dystroglycan. Our prior discussions with the FDA have all been about accelerated approval on, and the, I guess, the potential to use glycosylated alpha-dystroglycan as the surrogate. We weren't really expecting statistical significance on the functional improvement at 12 months, and that really wasn't, you know, the tenor of our prior discussion. Given that we have seen highly statistical significant functional improvement, as well as a clean safety profile, which we did expect, I think that's where we want to reopen discussions with the FDA. Your next question comes from the line of Anupam Rama with JP Morgan. Please go ahead. Hey, guys. Thanks so much for taking the question and congrats on the data. Christine, maybe I can follow up on your just prior comment. Anything more you can share on the nature and severity of some of the treatment emergent adverse events you saw in the treated group? Also, can you say anything about the baseline characteristics and the severity of the patients enrolled in the study just to help us further kind of put the efficacy that we're seeing into context? Thanks so much. Yeah. Thanks for that, Anupum. I think on the treatment emergent events, we aren't sharing a lot of detail right now only because we need to be mindful of the integrity of the ongoing study before we have the discussions with the FDA. What we've said, of course, is that there are no new ones that we've identified and that the safety profile is very consistent with phase two. I don't know, Doug, if you want to add any more color to that in terms of what we've hoped to discuss about. It's unfortunately a tricky question because the numbers are very low, and we want to avoid further impacting study integrity. There were no new TEAEs, certainly nothing associated with therapy. The safety and risk profile has not changed from what we've described previously. Yeah. Encouragingly, as you said as well, the attenuation rate was very low, and it was higher in the placebo arm. I think in terms of the baseline characteristics for the phase three, it's very consistent, actually, with our phase two study population. I don't know if that's anything else. Yeah. I mean, it's a mixed cohort, and we'll be presenting additional, we'll continue to present this in greater details moving forward. There's a mixed cohort of patients with homozygosity for L276I and patients with other FKRP genotypes that roughly matches the general population. The predominance were ambulatory patients because of the structure of this study. There were a sizable cohort of non-ambulatory patients enrolled as well that are incorporated in appropriate analyses, including forced vital capacity. This is a broad study that we believe will provide sufficient coverage for a relatively expansive label. Your next question comes from the line of Paul Toy with Goldman Sachs. Please go ahead. Hi. Good morning. Congratulations on the data, and thanks for taking our questions. My first question is, can you maybe comment on if the magnitude of benefit was the same in pediatric patients as it was in the adult patients just in the context of the natural history? I think your international enrollment was largely limited to adults, so maybe just some clarity on that would be helpful. My second question is, as sort of a first-in-class for this therapy, do you anticipate a potential FDA adcom might be held for this, just given the novelty of the category and just sort of the unknown treatment options for this particular disease? Thanks for taking our questions, and congrats again on the data. Thank you. On the pediatric subgroups, all the subgroup analyses are ongoing, so we'll disclose that at a later time. On the, sorry, what was the second part of the question? Adcom, right. Adcom. Prior to this data, I actually thought an adcom was more likely than not, and now I think it's the opposite. I think given the strength of the data, how robust it is, how consistent it is, how overwhelming and positive it is in the clean safety profile, I'm not really sure that there's, I don't know what we're going to discuss. I think it's less likely now. Your next question comes from the line of Jason Zemansky with Bank of America. Please go ahead. Good morning. Congrats on the data, and thanks for squeezing us in. I wanted to ask on your expectations over the long-term outcomes. I mean, granted, things are still early, but it did appear that the alpha-DG levels continued to improve somewhat over the 12 month interval. Is there the potential that longer-term exposure can drive even better responses? Alternatively, is there a limit to how much you can replace and at some level, you know, patients will decline at, you know, albeit a more modest level? Thank you. Yeah, thanks. I'll turn it over to Doug. Yeah. Obviously, we'll need to see ultimately. Our expectation, based on what we've seen from our natural history, from the natural history studies, what we've seen from the longer-term datasets from the University of Iowa, is that patients who are not treated will experience a continued ongoing and inexorable decline along the fashion that we're seeing in our placebo arm, and that will continue in the longer term. We believe that this demonstrates a change in trajectory. You know, the magnitude of that and, you know, the continued directionality obviously will remain to be seen. We expect that that gap and that difference between the treatment and placebo arms will continue to grow with longer and longer therapy. Again, that remains to be demonstrated with the data. One more thing, which is the data that we showed, that's the change from baseline. The one-year time point, we're essentially already doubled the baseline level of glycosylated alpha-DG. About 21%-22% has already increased by 23%. It's a remarkable increase already at 12 months. Yeah, just with that in context, what we believed was clinically meaningful was an absolute increase of 5%. The fact that we're getting a 17% increase already at three months is pretty meaningful. That concludes our question and answer session. I will turn the conference back over to Christine Siu for closing comments. All right. Thanks, everyone. I think, you know, based on the strength of the data, I think we're very excited about the potential here. It just could be very transformative for these patients, for this community, because we could offer really, you know, we could be first to market with an oral disease-modifying therapy. It's a functional improvement. We're excited. Thank you. Ladies and gentlemen, that does conclude today's conference call. Thank you for your participation, and you may now disconnect.

Speaker 16: Ladies and gentlemen, thank you for standing by. My name is Krista, and I will be your conference operator today. At this time, I would like to welcome everyone to the BridgeBio Pharma, Limb-girdle Muscular Dystrophy Type 2I/R9 FORTIFY phase three interim analysis results webinar. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question at that time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press 1. Thank you. I would now like to turn the conference over to Dr. Neil Kumar, Chief Executive Officer. Dr. Kumar, please go ahead. Ladies and gentlemen, thank you for standing by. ladies and gentlemen thank you for standing by My name is Krista, and I will be your conference operator today. my name is krista and i will be your conference operator today At this time, I would like to welcome everyone to the BridgeBio Pharma, Limb- girdle Muscular Dystrophy Type 2I/R9 FORTIFY phase three interim analysis results webinar. at this time i would like to welcome everyone to the bridgebio pharma limb- girdle muscular dystrophy type 2i/r9 fortify phase three interim analysis results webinar All lines have been placed on mute to prevent any background noise. all lines have been placed on mute to prevent any background noise After the speaker's remarks, there will be a question and answer session. after the speaker's remarks there will be a question and answer session If you would like to ask a question at that time, simply press star, followed by the number one on your telephone keypad. if you would like to ask a question at that time simply press star followed by the number one on your telephone keypad If you would like to withdraw your question, again, press 1 . if you would like to withdraw your question again press *1 Thank you. thank you I would now like to turn the conference over to Dr. Neil Kumar, Chief Executive Officer. i would now like to turn the conference over to dr neil kumar chief executive officer Dr. Kumar, please go ahead. dr kumar please go ahead

Speaker 10: Thanks, everyone, for joining this call. Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with Limb-girdle Muscular Dystrophy Type 2I/R9. The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current and future patients struggling with this condition. Before I set the corporate context for this readout, I want to begin with the most important slide in this document, slide four, a thank you to the amazing and inspiring patients and families, advocates, physicians, clinical research staff, and collaborating research partners that made this study possible. Thanks, everyone, for joining this call. thanks everyone for joining this call Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with Limb- girdle Muscular Dystrophy Type 2I/R9. together with our amazing team i'm grateful to be able to share with you on behalf of the extraordinary physicians patients families and caregivers involved the positive phase three results of our fortify clinical trial for patients with limb- girdle muscular dystrophy type 2i/r9 The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current and future patients struggling with this condition. the strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current and future patients struggling with this condition Before I set the corporate context for this readout, I want to begin with the most important slide in this document, slide four, a thank you to the amazing and inspiring patients and families, advocates, physicians, clinical research staff, and collaborating research partners that made this study possible. before i set the corporate context for this readout i want to begin with the most important slide in this document slide four a thank you to the amazing and inspiring patients and families advocates physicians clinical research staff and collaborating research partners that made this study possible As we have hopefully demonstrated in the past, across conditions as desperate and disparate as MOCD type A and ATTR cardiomyopathy, we recognize now our responsibility to the community that made this work possible and therefore plan to move expeditiously to provide this medicine to patients broadly. Turning to slide five, I'll take a brief moment to provide some corporate context for today's data. As many of you know, BridgeBio Pharma was founded almost 10 years ago to target well-described genetic diseases at their source. Our efficient R&D engine has helped generate almost 20 INDs and three approvals to date, and we hope to add BBP-418 to that list in short order. Today's data represent the first of three major current and upcoming phase three readouts for us, with results from our ADH1 and achondroplasia efforts expected in the near term as well. As we have hopefully demonstrated in the past, across conditions as desperate and disparate as MOCD type A and ATTR cardiomyopathy, we recognize now our responsibility to the community that made this work possible and therefore plan to move expeditiously to provide this medicine to patients broadly. as we have hopefully demonstrated in the past across conditions as desperate and disparate as mocd type a and attr cardiomyopathy we recognize now our responsibility to the community that made this work possible and therefore plan to move expeditiously to provide this medicine to patients broadly Turning to slide five, I'll take a brief moment to provide some corporate context for today's data. turning to slide five i'll take a brief moment to provide some corporate context for today's data As many of you know, BridgeBio Pharma was founded almost 10 years ago to target well-described genetic diseases at their source. as many of you know, bridgebio pharma was founded almost 10 years ago to target well-described genetic diseases at their source Our efficient R&D engine has helped generate almost 20 INDs and three approvals to date, and we hope to add BBP-418 to that list in short order. our efficient r&d engine has helped generate almost 20 inds and three approvals to date and we hope to add bbp-418 to that list in short order Today's data represent the first of three major current and upcoming phase three readouts for us, with results from our ADH1 and achondroplasia efforts expected in the near term as well. today's data represent the first of three major current and upcoming phase three readouts for us with results from our adh1 and achondroplasia efforts expected in the near term as well Together, these and ongoing earlier stage programs should provide, on a risk-adjusted basis, a reasonable tapestry of impact for the patients we serve and investors alike. Turning back to the program of the moment on slide six, I thought I'd make two final observations that pertain more broadly to our efforts. First, although we deploy many different modalities in an effort to target causal drivers of Mendelian disease, where we can, we often use small molecules. In many of the disease areas in which we play, there's sometimes a misconception that small molecules, while perhaps being more efficient to develop or safer, can't provide the type of efficacy other modalities can. Together, these and ongoing earlier stage programs should provide, on a risk-adjusted basis, a reasonable tapestry of impact for the patients we serve and investors alike. together these and ongoing earlier stage programs should provide on a risk-adjusted basis a reasonable tapestry of impact for the patients we serve and investors alike Turning back to the program of the moment on slide six, I thought I'd make two final observations that pertain more broadly to our efforts. turning back to the program of the moment on slide six i thought i'd make two final observations that pertain more broadly to our efforts First, although we deploy many different modalities in an effort to target causal drivers of Mendelian disease, where we can, we often use small molecules. first although we deploy many different modalities in an effort to target causal drivers of mendelian disease where we can we often use small molecules In many of the disease areas in which we play, there's sometimes a misconception that small molecules, while perhaps being more efficient to develop or safer, can't provide the type of efficacy other modalities can. in many of the disease areas in which we play there's sometimes a misconception that small molecules while perhaps being more efficient to develop or safer can't provide the type of efficacy other modalities can Here, with perhaps the most impressive data set generated to date in the muscular dystrophy space, we once again show that the quantitative impact on the causal genetic driver is what counts, and that small molecules can provide optimal impact safely and obviously in the most cost-efficient form for society in the long run. Secondly, we were profoundly enthused to observe improvement for the patients in this trial. It's not a new concept, but a good reminder that intervening to take away the biochemical insult can result not only in the halting of ongoing pathology, but indeed in improvement. Reliably improving patient lives is the ultimate aim for any therapeutic we develop, and BBP-418 has met that high bar. With that, I'll turn it over to Christine and team to tell you more about the specifics of this remarkable trial result and the next steps for this program. Here, with perhaps the most impressive data set generated to date in the muscular dystrophy space, we once again show that the quantitative impact on the causal genetic driver is what counts, and that small molecules can provide optimal impact safely and obviously in the most cost-efficient form for society in the long run. here with perhaps the most impressive data set generated to date in the muscular dystrophy space we once again show that the quantitative impact on the causal genetic driver is what counts and that small molecules can provide optimal impact safely and obviously in the most cost-efficient form for society in the long run Secondly, we were profoundly enthused to observe improvement for the patients in this trial. secondly we were profoundly enthused to observe improvement for the patients in this trial It's not a new concept, but a good reminder that intervening to take away the biochemical insult can result not only in the halting of ongoing pathology, but indeed in improvement. it's not a new concept but a good reminder that intervening to take away the biochemical insult can result not only in the halting of ongoing pathology but indeed in improvement Reliably improving patient lives is the ultimate aim for any therapeutic we develop, and BBP-418 has met that high bar. reliably improving patient lives is the ultimate aim for any therapeutic we develop and bbp-418 has met that high bar With that, I'll turn it over to Christine and team to tell you more about the specifics of this remarkable trial result and the next steps for this program. with that i'll turn it over to christine and team to tell you more about the specifics of this remarkable trial result and the next steps for this program

Speaker 14: Thanks, Neil. First, I'd like to thank our BridgeBio Pharma team who have worked at a high pace with high standards to achieve this milestone. I'd also like to thank the community of collaborators, patients, caregivers, investigators. Without them, this would not be possible. When I speak with patients, I'm first inspired by their courage and struck by their hope for a therapy. Because LGMD2I/R9 is a progressive disease, what they can believe in is something that could stop or slow the progressive loss of daily function. These data show BBP-418 could be transformative in not only slowing the loss, but improving clinical function too. On slide nine, the data are striking in how consistent and how robust it is across all key endpoints measured. Thanks, Neil. thanks neil First, I'd like to thank our BridgeBio Pharma team who have worked at a high pace with high standards to achieve this milestone. first i'd like to thank our bridgebio pharma team who have worked at a high pace with high standards to achieve this milestone I'd also like to thank the community of collaborators, patients, caregivers, investigators. i'd also like to thank the community of collaborators patients caregivers investigators Without them, this would not be possible. without them this would not be possible When I speak with patients, I'm first inspired by their courage and struck by their hope for a therapy. when i speak with patients i'm first inspired by their courage and struck by their hope for a therapy Because LGMD2I/R9 is a progressive disease, what they can believe in is something that could stop or slow the progressive loss of daily function. because lgmd2i/r9 is a progressive disease what they can believe in is something that could stop or slow the progressive loss of daily function These data show BBP-418 could be transformative in not only slowing the loss, but improving clinical function too. these data show bbp-418 could be transformative in not only slowing the loss but improving clinical function too On slide nine, the data are striking in how consistent and how robust it is across all key endpoints measured. on slide nine the data are striking in how consistent and how robust it is across all key endpoints measured The results were highly statistically significant for glycosylated alpha-dystroglycan at three months, at 12 months, serum creatine kinase at 12 months, and our functional measures, 100 m time test, and forced vital capacity at 12 months. On the next slide, we compare these results to our expectations. Relative to our base case, this was really a home run scenario. We expected robust biomarker changes in glycosylated alpha-dystroglycan and serum creatine kinase, which were demonstrated and exceeded our expectations. We did not expect statistical significance, however, on the functional endpoints. The study wasn't powered for statistical significance on functional endpoints, so the fact that we saw such high statistical significance on 100 m time test and forced vital capacity at 12 months is really quite remarkable. Not only did we see separation from placebo, we saw improvement in the treatment arm. The results were highly statistically significant for glycosylated alpha-dystroglycan at three months, at 12 months, serum creatine kinase at 12 months, and our functional measures, 100 m time test, and forced vital capacity at 12 months. the results were highly statistically significant for glycosylated alpha-dystroglycan at three months at 12 months serum creatine kinase at 12 months and our functional measures, 100 m time test and forced vital capacity at 12 months On the next slide, we compare these results to our expectations. on the next slide we compare these results to our expectations Relative to our base case, this was really a home run scenario. relative to our base case this was really a home run scenario We expected robust biomarker changes in glycosylated alpha-dystroglycan and serum creatine kinase, which were demonstrated and exceeded our expectations. we expected robust biomarker changes in glycosylated alpha-dystroglycan and serum creatine kinase which were demonstrated and exceeded our expectations We did not expect statistical significance, however, on the functional endpoints. we did not expect statistical significance however on the functional endpoints The study wasn't powered for statistical significance on functional endpoints, so the fact that we saw such high statistical significance on 100 m time test and forced vital capacity at 12 months is really quite remarkable. the study wasn't powered for statistical significance on functional endpoints so the fact that we saw such high statistical significance on 100 m time test and forced vital capacity at 12 months is really quite remarkable Not only did we see separation from placebo, we saw improvement in the treatment arm. not only did we see separation from placebo we saw improvement in the treatment arm This is remarkable and the first time that I'm really aware of any therapy demonstrating functional improvement in a randomized controlled study in limb girdle. This underscores the potential for BBP-418 first to market for a disease-modifying therapy for LGMD2I/R9. I will now turn it over to our Chief Medical Officer, Dr. Doug Sproul, to walk through the data. This is remarkable and the first time that I'm really aware of any therapy demonstrating functional improvement in a randomized controlled study in limb girdle. this is remarkable and the first time that i'm really aware of any therapy demonstrating functional improvement in a randomized controlled study in limb girdle This underscores the potential for BBP-418 first to market for a disease-modifying therapy for LGMD2I/R9. this underscores the potential for bbp-418 first to market for a disease-modifying therapy for lgmd2i/r9 I will now turn it over to our Chief Medical Officer, Dr. Doug Sproul, to walk through the data. i will now turn it over to our chief medical officer dr doug sproul to walk through the data

Speaker 3: Thank you, Christine, for that kind introduction. It is a distinct pleasure of mine to have the opportunity to present the top-line phase three FORTIFY interim analysis data. It is a special privilege as a member of this community to be able to present such impressive data. Before I present the data, I would be remiss without expressing the immense appreciation that we have for the patients and their families who have contributed and sacrificed so much to advance care and research in LGMD2I/R9. Particularly call out the tireless work of our patient advocate community partners and the many physicians, clinical trialists, caregivers, clinical research staff, and other collaborating research partners who have all contributed in such a major way to this data and the ongoing advances that we see in the field. Moving to slide 13, FORTIFY is our ongoing randomized placebo-controlled phase three study of BBP-418 versus placebo. Thank you, Christine, for that kind introduction. thank you christine for that kind introduction It is a distinct pleasure of mine to have the opportunity to present the top-line phase three FORTIFY interim analysis data. it is a distinct pleasure of mine to have the opportunity to present the top-line phase three fortify interim analysis data It is a special privilege as a member of this community to be able to present such impressive data. it is a special privilege as a member of this community to be able to present such impressive data Before I present the data, I would be remiss without expressing the immense appreciation that we have for the patients and their families who have contributed and sacrificed so much to advance care and research in LGMD2I/R9. before i present the data i would be remiss without expressing the immense appreciation that we have for the patients and their families who have contributed and sacrificed so much to advance care and research in lgmd2i/r9 Particularly call out the tireless work of our patient advocate community partners and the many physicians, clinical trialists, caregivers, clinical research staff, and other collaborating research partners who have all contributed in such a major way to this data and the ongoing advances that we see in the field. particularly call out the tireless work of our patient advocate community partners and the many physicians clinical trialists caregivers clinical research staff and other collaborating research partners who have all contributed in such a major way to this data and the ongoing advances that we see in the field Moving to slide 13, FORTIFY is our ongoing randomized placebo-controlled phase three study of BBP-418 versus placebo. moving to slide 13 fortify is our ongoing randomized placebo-controlled phase three study of bbp-418 versus placebo This is a well-controlled and balanced study comparing patients treated with BBP-418 versus placebo in a double-blind randomized controlled manner. Patients are randomized two to one to receive BBP-418 versus placebo. We are reporting the top-line results of our interim analysis that involved the first 72 patients to complete at least one year of clinical study. I'll be discussing our interim endpoints that we have assessed in a formal, statistically rigorous manner. That is including our biomarker glycosylated alpha-dystroglycan, the change from baseline at three months as well as at 12 months. We are also assessing creatine kinase, which is a widely used and well-established marker of muscle injury and breakdown. We are assessing two important and clinically meaningful clinical measures widely used in neuromuscular research. The first is the 100-meter time test, which is an assessment of ambulatory function as well as fatigue. This is a well-controlled and balanced study comparing patients treated with BBP-418 versus placebo in a double-blind randomized controlled manner. this is a well-controlled and balanced study comparing patients treated with bbp-418 versus placebo in a double-blind randomized controlled manner Patients are randomized two to one to receive BBP-418 versus placebo. patients are randomized two to one to receive bbp-418 versus placebo We are reporting the top-line results of our interim analysis that involved the first 72 patients to complete at least one year of clinical study. we are reporting the top-line results of our interim analysis that involved the first 72 patients to complete at least one year of clinical study I'll be discussing our interim endpoints that we have assessed in a formal, statistically rigorous manner. i'll be discussing our interim endpoints that we have assessed in a formal statistically rigorous manner That is including our biomarker glycosylated alpha-dystroglycan, the change from baseline at three months as well as at 12 months. that is including our biomarker glycosylated alpha-dystroglycan the change from baseline at three months as well as at 12 months We are also assessing creatine kinase, which is a widely used and well-established marker of muscle injury and breakdown. we are also assessing creatine kinase which is a widely used and well-established marker of muscle injury and breakdown We are assessing two important and clinically meaningful clinical measures widely used in neuromuscular research. we are assessing two important and clinically meaningful clinical measures widely used in neuromuscular research The first is the 100-meter time test, which is an assessment of ambulatory function as well as fatigue. the first is the 100-meter time test which is an assessment of ambulatory function as well as fatigue The second is a broadly used measure of pulmonary function, forced vital capacity. As I've mentioned, this is a double-blind randomized control trial. The placebo and BBP-418 arms were stratified by age, by ambulatory status, as well as by genotype to allow a well-balanced and well-controlled study that I am eager and proud to present today. Before I get into the clinical markers, I wanted to give my colleague Uma Sinha the opportunity to discuss the dramatic results from our alpha-dystroglycan glycosylation bioassay. With that, I'll pass the baton to her to speak. The second is a broadly used measure of pulmonary function, forced vital capacity. the second is a broadly used measure of pulmonary function forced vital capacity As I've mentioned, this is a double-blind randomized control trial. as i've mentioned this is a double-blind randomized control trial The placebo and BBP-418 arms were stratified by age, by ambulatory status, as well as by genotype to allow a well-balanced and well-controlled study that I am eager and proud to present today. the placebo and bbp-418 arms were stratified by age by ambulatory status as well as by genotype to allow a well-balanced and well-controlled study that i am eager and proud to present today Before I get into the clinical markers, I wanted to give my colleague Uma Sinha the opportunity to discuss the dramatic results from our alpha-dystroglycan glycosylation bioassay. before i get into the clinical markers i wanted to give my colleague uma sinha the opportunity to discuss the dramatic results from our alpha-dystroglycan glycosylation bioassay With that, I'll pass the baton to her to speak. with that i'll pass the baton to her to speak

Speaker 12: Thank you, Doug. It's an incredible pleasure and a source of pride to be able to present the biomarker data that the whole team has worked long and hard on. Most importantly, the patient samples, which allowed us to develop the biomarker assay. I'm incredibly grateful for those. First, let me remind everybody about the mechanisms of this disease. LGMD2I/R9 is caused by mutations in FKRP that lead to decreased enzymatic activity of FKRP. This in turn reduces the extent of glycosylation of alpha-DG. Hypoglycosylation of alpha-DG is a core defect in the disease, and this is consistent with the genotype-phenotype association of L276I mutant and other heterozygous FKRP genotypes that are in the literature, and we have also tested in our natural history study. Thank you, Doug. thank you doug It's an incredible pleasure and a source of pride to be able to present the biomarker data that the whole team has worked long and hard on. it's an incredible pleasure and a source of pride to be able to present the biomarker data that the whole team has worked long and hard on Most importantly, the patient samples, which allowed us to develop the biomarker assay. most importantly the patient samples which allowed us to develop the biomarker assay I'm incredibly grateful for those. i'm incredibly grateful for those First, let me remind everybody about the mechanisms of this disease. first let me remind everybody about the mechanisms of this disease LGMD2I/R9 is caused by mutations in FKRP that lead to decreased enzymatic activity of FKRP. lgmd2i/r9 is caused by mutations in fkrp that lead to decreased enzymatic activity of fkrp This in turn reduces the extent of glycosylation of alpha-DG. this in turn reduces the extent of glycosylation of alpha-dg Hypoglycosylation of alpha-DG is a core defect in the disease, and this is consistent with the genotype-phenotype association of L276I mutant and other heterozygous FKRP genotypes that are in the literature, and we have also tested in our natural history study. hypoglycosylation of alpha-dg is a core defect in the disease and this is consistent with the genotype-phenotype association of l276i mutant and other heterozygous fkrp genotypes that are in the literature and we have also tested in our natural history study The hypothesis that we are testing here is that by BBP-418 dosing, we are targeting the disease at its source, restoring glycosylation of alpha-dystroglycan, and thereby enabling the muscle to continue binding laminin at the expected level. We have developed a proprietary validated western blot assay to accurately and reliably measure glycosylated alpha-DG directly in skeletal muscle tissue. This is important on multiple levels. It's a proprietary assay. FDA has reviewed our approach and agreed that it is reasonable. What's novel about this assay? The assay uses two antibodies for immune detection of alpha-DG. One directly measures glycosylated alpha-DG, and the other measures the core protein. It's important to remember that the first antibody is detecting the functional moiety, the moiety responsible for laminin binding. In this slide, we're showing you representative data from phase two. Both glycosylated and non-glycosylated protein is being shown here. The hypothesis that we are testing here is that by BBP-418 dosing, we are targeting the disease at its source, restoring glycosylation of alpha-dystroglycan, and thereby enabling the muscle to continue binding laminin at the expected level. the hypothesis that we are testing here is that by bbp-418 dosing we are targeting the disease at its source restoring glycosylation of alpha-dystroglycan and thereby enabling the muscle to continue binding laminin at the expected level We have developed a proprietary validated western blot assay to accurately and reliably measure glycosylated alpha-DG directly in skeletal muscle tissue. we have developed a proprietary validated western blot assay to accurately and reliably measure glycosylated alpha-dg directly in skeletal muscle tissue This is important on multiple levels. this is important on multiple levels It's a proprietary assay. it's a proprietary assay FDA has reviewed our approach and agreed that it is reasonable. fda has reviewed our approach and agreed that it is reasonable What's novel about this assay? what's novel about this assay The assay uses two antibodies for immune detection of alpha-DG. the assay uses two antibodies for immune detection of alpha-dg One directly measures glycosylated alpha-DG, and the other measures the core protein. one directly measures glycosylated alpha-dg and the other measures the core protein It's important to remember that the first antibody is detecting the functional moiety, the moiety responsible for laminin binding. it's important to remember that the first antibody is detecting the functional moiety the moiety responsible for laminin binding In this slide, we're showing you representative data from phase two. in this slide we're showing you representative data from phase two Both glycosylated and non-glycosylated protein is being shown here. both glycosylated and non-glycosylated protein is being shown here As you can see in the untreated patients, there's barely a signal for the glycosylated alpha-DG protein component. In this data, we have confirmed that upon BBP-418 dosing, already at three months, we are detecting an increase in the glycosylated alpha-DG level, which is sustained at the six-month level. This was the dose-finding phase two data, so it allowed us to build on our hypothesis. Another thing that we have done is use this validated assay to measure baseline levels of glycosylated alpha-DG across our natural history, phase two, and phase three studies. I'm happy to report that the results have been consistent and given us more faith in what the assay is measuring. As Doug has already mentioned, the change from baseline in glycosylated alpha-dystroglycan was the primary endpoint of the phase three trial. We have observed a robust and rapid increase in glycosylated alpha-dystroglycan at three months. As you can see in the untreated patients, there's barely a signal for the glycosylated alpha-DG protein component. as you can see in the untreated patients there's barely a signal for the glycosylated alpha-dg protein component In this data, we have confirmed that upon BBP-418 dosing, already at three months, we are detecting an increase in the glycosylated alpha-DG level, which is sustained at the six-month level. in this data we have confirmed that upon bbp-418 dosing already at three months we are detecting an increase in the glycosylated alpha-dg level which is sustained at the six-month level This was the dose-finding phase two data, so it allowed us to build on our hypothesis. this was the dose-finding phase two data so it allowed us to build on our hypothesis Another thing that we have done is use this validated assay to measure baseline levels of glycosylated alpha-DG across our natural history, phase two, and phase three studies. another thing that we have done is use this validated assay to measure baseline levels of glycosylated alpha-dg across our natural history phase two and phase three studies I'm happy to report that the results have been consistent and given us more faith in what the assay is measuring. i'm happy to report that the results have been consistent and given us more faith in what the assay is measuring As Doug has already mentioned, the change from baseline in glycosylated alpha-dystroglycan was the primary endpoint of the phase three trial. as doug has already mentioned the change from baseline in glycosylated alpha-dystroglycan was the primary endpoint of the phase three trial We have observed a robust and rapid increase in glycosylated alpha-dystroglycan at three months. we have observed a robust and rapid increase in glycosylated alpha-dystroglycan at three months I'd like to focus on the three salient points that this data set is telling us. One is that the change from baseline in alpha-dystroglycan is robust and seen rapidly at the three-month time point, very statistically significant. This increase is sustained through the 12-month period. The third point I'd like to remind everybody about is that our knowledge in the natural history study as to how the baseline levels of glycosylated alpha-dystroglycan behave, that has been confirmed in this study. There was essentially no change in the placebo arm. Our preclinical data in mouse models, as well as in the natural history study, told us that targeting a 5% change in glycosylated alpha-dystroglycan would be expected to be a clinically meaningful benefit in the patient population. I'd like to focus on the three salient points that this data set is telling us. i'd like to focus on the three salient points that this data set is telling us One is that the change from baseline in alpha-dystroglycan is robust and seen rapidly at the three-month time point, very statistically significant. one is that the change from baseline in alpha-dystroglycan is robust and seen rapidly at the three-month time point very statistically significant This increase is sustained through the 12-month period. this increase is sustained through the 12-month period The third point I'd like to remind everybody about is that our knowledge in the natural history study as to how the baseline levels of glycosylated alpha-dystroglycan behave, that has been confirmed in this study. the third point i'd like to remind everybody about is that our knowledge in the natural history study as to how the baseline levels of glycosylated alpha-dystroglycan behave that has been confirmed in this study There was essentially no change in the placebo arm. there was essentially no change in the placebo arm Our preclinical data in mouse models, as well as in the natural history study, told us that targeting a 5% change in glycosylated alpha-dystroglycan would be expected to be a clinically meaningful benefit in the patient population. our preclinical data in mouse models as well as in the natural history study told us that targeting a 5% change in glycosylated alpha-dystroglycan would be expected to be a clinically meaningful benefit in the patient population As you can see from this data, we saw an increase of 17% of control at the three-month time point, and the effect was sustained at the 12-month time point with a 23% change from baseline. Target was 5%, so we have definitely exceeded expectations here. I'd like to now turn this over to Doug to delve deeper into the clinical data. As you can see from this data, we saw an increase of 17% of control at the three-month time point, and the effect was sustained at the 12-month time point with a 23% change from baseline. as you can see from this data we saw an increase of 17% of control at the three-month time point and the effect was sustained at the 12-month time point with a 23% change from baseline Target was 5%, so we have definitely exceeded expectations here. target was 5% so we have definitely exceeded expectations here I'd like to now turn this over to Doug to delve deeper into the clinical data. i'd like to now turn this over to doug to delve deeper into the clinical data

Speaker 3: Thank you, Uma, for that fantastic overview of the glycosylated alpha-dystroglycan bioassay. I'd like to build upon those amazing and dramatic results that we're seeing from our bioassay, which shows an approximate doubling in glycosylated alpha-dystroglycan levels amongst patients treated with BBP-418. We're seeing a similarly dramatic, large, statistically significant reduction in serum creatine kinase amongst patients treated with BBP-418, a difference of 82%, a decrease of 82% from baseline at 12 months. This is an amazing observation, just to put it in a little bit of context, a large proportion of patients treated with BBP-418 achieve levels that are within one or two times the upper limit of normal. This suggests a marked reduction in muscle breakdown that's indicated by this reduction in serum creatine kinase. We demonstrated with the bioassay that we have an impact on cellular physiology, that we're improving and increasing glycosylated alpha-dystroglycan levels. Thank you, Uma, for that fantastic overview of the glycosylated alpha-dystroglycan bioassay. thank you uma for that fantastic overview of the glycosylated alpha-dystroglycan bioassay I'd like to build upon those amazing and dramatic results that we're seeing from our bioassay, which shows an approximate doubling in glycosylated alpha-dystroglycan levels amongst patients treated with BBP-418. i'd like to build upon those amazing and dramatic results that we're seeing from our bioassay which shows an approximate doubling in glycosylated alpha-dystroglycan levels amongst patients treated with bbp-418 We're seeing a similarly dramatic, large, statistically significant reduction in serum creatine kinase amongst patients treated with BBP-418, a difference of 82%, a decrease of 82% from baseline at 12 months. we're seeing a similarly dramatic large statistically significant reduction in serum creatine kinase amongst patients treated with bbp-418 a difference of 82% a decrease of 82% from baseline at 12 months This is an amazing observation, just to put it in a little bit of context, a large proportion of patients treated with BBP-418 achieve levels that are within one or two times the upper limit of normal. this is an amazing observation just to put it in a little bit of context a large proportion of patients treated with bbp-418 achieve levels that are within one or two times the upper limit of normal This suggests a marked reduction in muscle breakdown that's indicated by this reduction in serum creatine kinase. this suggests a marked reduction in muscle breakdown that's indicated by this reduction in serum creatine kinase We demonstrated with the bioassay that we have an impact on cellular physiology, that we're improving and increasing glycosylated alpha-dystroglycan levels. we demonstrated with the bioassay that we have an impact on cellular physiology that we're improving and increasing glycosylated alpha-dystroglycan levels That's translating to a large and important reduction in muscle breakdown that's measured using and demonstrated using serum creatine kinase. These are results that we expected to see, to be perfectly frank. We have confidence in this compound. What is most exciting is what I'm going to talk about in the next few slides, that this physiologic effect, this biologic effect that we're able to demonstrate now, excitingly translates as well to signs and signals of meaningful and important clinical impact. We are excited to present data that is demonstrating that third link in the chain, that we're demonstrating the impact on the physiology that's translating to reduced muscle breakdown. Now we're able to report, excitingly, an impact on clinical function as well. We are observing a 0.27 m/s improvement amongst patients treated with BBP-418 versus placebo in the 100 m time test. That's translating to a large and important reduction in muscle breakdown that's measured using and demonstrated using serum creatine kinase. that's translating to a large and important reduction in muscle breakdown that's measured using and demonstrated using serum creatine kinase These are results that we expected to see, to be perfectly frank. these are results that we expected to see to be perfectly frank We have confidence in this compound. we have confidence in this compound What is most exciting is what I'm going to talk about in the next few slides, that this physiologic effect, this biologic effect that we're able to demonstrate now, excitingly translates as well to signs and signals of meaningful and important clinical impact. what is most exciting is what i'm going to talk about in the next few slides that this physiologic effect this biologic effect that we're able to demonstrate now excitingly translates as well to signs and signals of meaningful and important clinical impact We are excited to present data that is demonstrating that third link in the chain, that we're demonstrating the impact on the physiology that's translating to reduced muscle breakdown. we are excited to present data that is demonstrating that third link in the chain that we're demonstrating the impact on the physiology that's translating to reduced muscle breakdown Now we're able to report, excitingly, an impact on clinical function as well. now we're able to report excitingly an impact on clinical function as well We are observing a 0.27 m/s improvement amongst patients treated with BBP-418 versus placebo in the 100 m time test. we are observing a 0.27 m/s improvement amongst patients treated with bbp-418 versus placebo in the 100 m time test To put a little bit of clinical context, the 100 m time test is a broadly used clinical and clinical research tool to assess ambulatory function and fatigue in patients with neuromuscular diseases. As we have seen in the natural history of the disease and demonstrated in our placebo arm, we see a consistent and inexorable decline in performance on this scale. We see a 0.12 m/s decline in patients treated with placebo. In contrast, we're seeing an improvement in patients treated with BBP-418 in their velocity of performance on the 100 m time test. This translates to an approximately 14 s faster performance amongst patients treated with BBP-418 when compared with patients treated with placebo as far as the time to complete this test. This is a statistically significant result, and it's a clinically meaningful result that we're seeing in patients treated with BBP-418 on their ambulatory function. To put a little bit of clinical context, the 100 m time test is a broadly used clinical and clinical research tool to assess ambulatory function and fatigue in patients with neuromuscular diseases. to put a little bit of clinical context the 100 m time test is a broadly used clinical and clinical research tool to assess ambulatory function and fatigue in patients with neuromuscular diseases As we have seen in the natural history of the disease and demonstrated in our placebo arm, we see a consistent and inexorable decline in performance on this scale. as we have seen in the natural history of the disease and demonstrated in our placebo arm we see a consistent and inexorable decline in performance on this scale We see a 0.12 m/s decline in patients treated with placebo. we see a 0.12 m/s decline in patients treated with placebo In contrast, we're seeing an improvement in patients treated with BBP-418 in their velocity of performance on the 100 m time test. in contrast we're seeing an improvement in patients treated with bbp-418 in their velocity of performance on the 100 m time test This translates to an approximately 14 s faster performance amongst patients treated with BBP-418 when compared with patients treated with placebo as far as the time to complete this test. this translates to an approximately 14 s faster performance amongst patients treated with bbp-418 when compared with patients treated with placebo as far as the time to complete this test This is a statistically significant result, and it's a clinically meaningful result that we're seeing in patients treated with BBP-418 on their ambulatory function. this is a statistically significant result and it's a clinically meaningful result that we're seeing in patients treated with bbp-418 on their ambulatory function Moving to the next slide, we're seeing a similarly dramatic and remarkable and improving performance in pulmonary function in patients treated with BBP-418 versus placebo as well. Amongst patients treated with BBP-418, we see a 3% increase in percent predicted volume from baseline, which represents an approximately 5% increase in percent predicted volume versus placebo. Taking a step back, pulmonary function is a critical system impacted in patients with LGMD2I, has a marked impact on morbidity and mortality. Forced vital capacity is measured in liters, but then adjusted for the gender, height, weight, age of a patient to give a percentage of how they should perform on this test. What we know from the natural history is that we see an inexorable 2% decline and loss year upon year upon year upon year, and that's actually seen in our placebo arm as well. Moving to the next slide, we're seeing a similarly dramatic and remarkable and improving performance in pulmonary function in patients treated with BBP-418 versus placebo as well. moving to the next slide we're seeing a similarly dramatic and remarkable and improving performance in pulmonary function in patients treated with bbp-418 versus placebo as well Amongst patients treated with BBP-418, we see a 3% increase in percent predicted volume from baseline, which represents an approximately 5% increase in percent predicted volume versus placebo. amongst patients treated with bbp-418 we see a 3% increase in percent predicted volume from baseline which represents an approximately 5% increase in percent predicted volume versus placebo Taking a step back, pulmonary function is a critical system impacted in patients with LGMD2I, has a marked impact on morbidity and mortality. taking a step back pulmonary function is a critical system impacted in patients with lgmd2i has a marked impact on morbidity and mortality Forced vital capacity is measured in liters, but then adjusted for the gender, height, weight, age of a patient to give a percentage of how they should perform on this test. forced vital capacity is measured in liters but then adjusted for the gender height weight age of a patient to give a percentage of how they should perform on this test What we know from the natural history is that we see an inexorable 2% decline and loss year upon year upon year upon year, and that's actually seen in our placebo arm as well. what we know from the natural history is that we see an inexorable 2% decline and loss year upon year upon year upon year and that's actually seen in our placebo arm as well In contrast, patients treated with BBP-418 have experienced an improvement in pulmonary function, an improvement in forced vital capacity that represents a 5% difference between the percentage predicted volume in one year between patients treated with placebo versus patients treated with BBP-418. This is a broadly clinically meaningful as well as statistically significant result that we're observing in patients treated with BBP-418 in this study. This summarizes, and not to beat a dead horse, but frankly to beat a dead horse, we're seeing not just stability, we're seeing not just a slowing of the reduction in loss compared with placebo, but we're seeing an absolute and statistically significant and clinically meaningful improvement in patients treated with BBP-418, not just with placebo, but also with their baseline status. That's a remarkable and really unprecedented result, particularly in the context of a double-blind randomized clinical trial. In contrast, patients treated with BBP-418 have experienced an improvement in pulmonary function, an improvement in forced vital capacity that represents a 5% difference between the percentage predicted volume in one year between patients treated with placebo versus patients treated with BBP-418. in contrast patients treated with bbp-418 have experienced an improvement in pulmonary function an improvement in forced vital capacity that represents a 5% difference between the percentage predicted volume in one year between patients treated with placebo versus patients treated with bbp-418 This is a broadly clinically meaningful as well as statistically significant result that we're observing in patients treated with BBP-418 in this study. this is a broadly clinically meaningful as well as statistically significant result that we're observing in patients treated with bbp-418 in this study This summarizes, and not to beat a dead horse, but frankly to beat a dead horse, we're seeing not just stability, we're seeing not just a slowing of the reduction in loss compared with placebo, but we're seeing an absolute and statistically significant and clinically meaningful improvement in patients treated with BBP-418, not just with placebo, but also with their baseline status. this summarizes and not to beat a dead horse but frankly to beat a dead horse we're seeing not just stability we're seeing not just a slowing of the reduction in loss compared with placebo but we're seeing an absolute and statistically significant and clinically meaningful improvement in patients treated with bbp-418 not just with placebo but also with their baseline status That's a remarkable and really unprecedented result, particularly in the context of a double-blind randomized clinical trial. that's a remarkable and really unprecedented result particularly in the context of a double-blind randomized clinical trial This is the most impressive placebo-controlled data, in my opinion, in the LGMD space by a wide margin, perhaps in the entire muscle disease community to this date. I'm extraordinarily proud and excited to have had the opportunity to present this data to you today. I'm equally proud and happy to report that we have a continued highly favorable safety profile of BBP-418. We have no new or unexpected safety findings that have been observed in our phase three study. These are results that are consistent with our phase two study, consistent with everything that we previously reported. We have a low discontinuation rate overall. It's higher in the placebo group. We have no treatment-related serious TEAEs that have been observed in our phase three study. This is the most impressive placebo-controlled data, in my opinion, in the LGMD space by a wide margin, perhaps in the entire muscle disease community to this date. this is the most impressive placebo-controlled data in my opinion in the lgmd space by a wide margin perhaps in the entire muscle disease community to this date I'm extraordinarily proud and excited to have had the opportunity to present this data to you today. i'm extraordinarily proud and excited to have had the opportunity to present this data to you today I'm equally proud and happy to report that we have a continued highly favorable safety profile of BBP-418. i'm equally proud and happy to report that we have a continued highly favorable safety profile of bbp-418 We have no new or unexpected safety findings that have been observed in our phase three study. we have no new or unexpected safety findings that have been observed in our phase three study These are results that are consistent with our phase two study, consistent with everything that we previously reported. these are results that are consistent with our phase two study consistent with everything that we previously reported We have a low discontinuation rate overall. we have a low discontinuation rate overall It's higher in the placebo group. it's higher in the placebo group We have no treatment-related serious TEAEs that have been observed in our phase three study. we have no treatment-related serious teaes that have been observed in our phase three study The interim analysis continues to support that favorable risk profile as well as what I would consider a much increased benefit profile of the product. We're excited to present these top-line results today. What we've executed on to date sets the stage for an ambitious year and years ahead for our program, and we're extremely excited to move this program forward aggressively into the commercial phase of development. We plan to engage the FDA to discuss our pathway for NDA submission later this year or in early 2026. We intend to present the broader phase three data from our FORTIFY interim analysis results at the Muscular Dystrophy Association Clinical and Scientific Conference in March of 2026. The interim analysis continues to support that favorable risk profile as well as what I would consider a much increased benefit profile of the product. the interim analysis continues to support that favorable risk profile as well as what i would consider a much increased benefit profile of the product We're excited to present these top-line results today. we're excited to present these top-line results today What we've executed on to date sets the stage for an ambitious year and years ahead for our program, and we're extremely excited to move this program forward aggressively into the commercial phase of development. what we've executed on to date sets the stage for an ambitious year and years ahead for our program and we're extremely excited to move this program forward aggressively into the commercial phase of development We plan to engage the FDA to discuss our pathway for NDA submission later this year or in early 2026. we plan to engage the fda to discuss our pathway for nda submission later this year or in early 2026 We intend to present the broader phase three data from our FORTIFY interim analysis results at the Muscular Dystrophy Association Clinical and Scientific Conference in March of 2026. we intend to present the broader phase three data from our fortify interim analysis results at the muscular dystrophy association clinical and scientific conference in march of 2026 We furthermore intend to file an NDA with the FDA in the first half of 2026 and anticipate a US approval and commercial launch of BBP-418 to treat patients with LGMD2I/R9, potentially in late 2026 or early 2027. With that, I would like to introduce my colleague Matthew Outten, our Chief Commercial Officer, who will present our overall commercial strategy. We furthermore intend to file an NDA with the FDA in the first half of 2026 and anticipate a US approval and commercial launch of BBP-418 to treat patients with LGMD2I/R9, potentially in late 2026 or early 2027. we furthermore intend to file an nda with the fda in the first half of 2026 and anticipate a us approval and commercial launch of bbp-418 to treat patients with lgmd2i/r9 potentially in late 2026 or early 2027 With that, I would like to introduce my colleague Matthew Outten, our Chief Commercial Officer, who will present our overall commercial strategy. with that i would like to introduce my colleague matthew outten our chief commercial officer who will present our overall commercial strategy

Speaker 15: We are very excited about the data discussed today, which set the stage for BridgeBio Pharma's next commercial launch. Over the past 18 months, we've been preparing for this moment, building on the successful launch of Attruby to establish a robust commercial foundation across all functions, including market access, operations, analytics, and marketing. We will now leverage this infrastructure to launch BBP-418, supported by a dedicated field sales team that we have been proactively planning in anticipation of today's results. Our proven launch playbook will enable rapid mobilization for a launch that positions BBP-418 as the standard of care in LGMD2I/R9. We will continue to drive education and awareness as we move toward approval. It's important to remember that today represents the first and only positive data in LGMD2I/R9, a major milestone on our path to approval and for the community that we serve. We are very excited about the data discussed today, which set the stage for BridgeBio Pharma's next commercial launch. we are very excited about the data discussed today which set the stage for bridgebio pharma's next commercial launch Over the past 18 months, we've been preparing for this moment, building on the successful launch of Attruby to establish a robust commercial foundation across all functions, including market access, operations, analytics, and marketing. over the past 18 months we've been preparing for this moment building on the successful launch of attruby to establish a robust commercial foundation across all functions including market access operations analytics and marketing We will now leverage this infrastructure to launch BBP-418, supported by a dedicated field sales team that we have been proactively planning in anticipation of today's results. we will now leverage this infrastructure to launch bbp-418 supported by a dedicated field sales team that we have been proactively planning in anticipation of today's results Our proven launch playbook will enable rapid mobilization for a launch that positions BBP-418 as the standard of care in LGMD2I/R9. our proven launch playbook will enable rapid mobilization for a launch that positions bbp-418 as the standard of care in lgmd2i/r9 We will continue to drive education and awareness as we move toward approval. we will continue to drive education and awareness as we move toward approval It's important to remember that today represents the first and only positive data in LGMD2I/R9, a major milestone on our path to approval and for the community that we serve. it's important to remember that today represents the first and only positive data in lgmd2i/r9 a major milestone on our path to approval and for the community that we serve We look forward to sharing more about our commercial strategy as we get closer to approval. For today, there are two key takeaways. First, the data are as strong as we could hope for heading into launch. Second, our commercial organization is ready to execute, drawing on the same experienced teams that successfully brought Atrubi to the market. We are poised to do it again with BBP-418. With that, we will now open the discussion and start the Q&A portion of the call. We look forward to sharing more about our commercial strategy as we get closer to approval. we look forward to sharing more about our commercial strategy as we get closer to approval For today, there are two key takeaways. for today there are two key takeaways First, the data are as strong as we could hope for heading into launch. first the data are as strong as we could hope for heading into launch Second, our commercial organization is ready to execute, drawing on the same experienced teams that successfully brought Atrubi to the market. second our commercial organization is ready to execute drawing on the same experienced teams that successfully brought atrubi to the market We are poised to do it again with BBP-418. we are poised to do it again with bbp-418 With that, we will now open the discussion and start the Q&A portion of the call. with that we will now open the discussion and start the q&a portion of the call

Speaker 16: Thank you. We will now begin the question and answer. Thank you. thank you We will now begin the question and answer. we will now begin the question and answer

Speaker 10: Thanks, everyone, for joining this call. Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with limb girdle muscular dystrophy type 2I/R9. The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current. Thanks, everyone, for joining this call. thanks everyone for joining this call Together with our amazing team, I'm grateful to be able to share with you, on behalf of the extraordinary physicians, patients, families, and caregivers involved, the positive phase three results of our FORTIFY clinical trial for patients with limb girdle muscular dystrophy type 2I/R9. together with our amazing team i'm grateful to be able to share with you on behalf of the extraordinary physicians patients families and caregivers involved the positive phase three results of our fortify clinical trial for patients with limb girdle muscular dystrophy type 2i/r9 The strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current. the strongly positive and consistent data the community worked tirelessly to generate come together at this moment to portend a new and better day for current

Speaker 16: If you would like to ask a question, please press 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, again, press star one. We also ask that you limit yourself to one question. Your first question comes from Tyler Van Buren with TD Cowen. Please go ahead. If you would like to ask a question, please press 1 on your telephone keypad to raise your hand and join the queue. if you would like to ask a question please press *1 on your telephone keypad to raise your hand and join the queue If you would like to withdraw your question, again, press star one. if you would like to withdraw your question again press star one We also ask that you limit yourself to one question. we also ask that you limit yourself to one question Your first question comes from Tyler Van Buren with TD Cowen. your first question comes from tyler van buren with td cowen Please go ahead. please go ahead

Speaker 2: Great. Good morning, guys. Congratulations on the tremendous results. It looks like the results exceeded your home run scenario for the interim. I'm curious just to better understand what you think explains the outperformance. The 5% FVC benefit seems striking. Could you elaborate on the clinical significance of that 5% as well as the 14 s improvement on the functional outcomes? Why would the FDA allow patients to continue on placebo for another two years given these data? Great. great Good morning, guys. good morning guys Congratulations on the tremendous results. congratulations on the tremendous results It looks like the results exceeded your home run scenario for the interim. it looks like the results exceeded your home run scenario for the interim I'm curious just to better understand what you think explains the outperformance. i'm curious just to better understand what you think explains the outperformance The 5% FVC benefit seems striking. the 5% fvc benefit seems striking Could you elaborate on the clinical significance of that 5% as well as the 14 s improvement on the functional outcomes? could you elaborate on the clinical significance of that 5% as well as the 14 s improvement on the functional outcomes Why would the FDA allow patients to continue on placebo for another two years given these data? why would the fda allow patients to continue on placebo for another two years given these data

Speaker 14: All right. Thanks, Tyler. I don't think that was one question, but we'd love to answer all of them. I'm going to turn it over to our team advisor. All right. all right Thanks, Tyler. thanks tyler I don't think that was one question, but we'd love to answer all of them. i don't think that was one question but we'd love to answer all of them I'm going to turn it over to our team advisor. i'm going to turn it over to our team advisor

Speaker 3: Hi, this is Doug Sproul. I'll address the first question, which was regarding why we saw the results that we did and whether we were surprised by the results. I have personal belief in this compound. Personally, this was my hope and expect hope that we would see this. I believe that this product would have demonstrated this at any point. My biggest concern, frankly, was the endpoints and the ability to demonstrate a material effect over a relatively brief period of time. There are two aspects, I think, that drive how we were approaching the study and explain the outside results. The first is that our study was structured around the concept of stability. It's been reiterated over and over again from the community that just stabilizing the disease, stopping it from getting worse, was an important advance that they would consider a strong win. Hi, this is Doug Sproul. hi this is doug sproul I'll address the first question, which was regarding why we saw the results that we did and whether we were surprised by the results. i'll address the first question which was regarding why we saw the results that we did and whether we were surprised by the results I have personal belief in this compound. i have personal belief in this compound Personally, this was my hope and expect hope that we would see this. personally this was my hope and expect hope that we would see this I believe that this product would have demonstrated this at any point. i believe that this product would have demonstrated this at any point My biggest concern, frankly, was the endpoints and the ability to demonstrate a material effect over a relatively brief period of time. There are two aspects, I think, that drive how we were approaching the study and explain the outside results. my biggest concern frankly was the endpoints and the ability to demonstrate a material effect over a relatively brief period of time. there are two aspects i think that drive how we were approaching the study and explain the outside results The first is that our study was structured around the concept of stability. the first is that our study was structured around the concept of stability It's been reiterated over and over again from the community that just stabilizing the disease, stopping it from getting worse, was an important advance that they would consider a strong win. it's been reiterated over and over again from the community that just stabilizing the disease stopping it from getting worse was an important advance that they would consider a strong win Our program was based around that as being kind of the minimal efficacy that would be clinically and important for patients and really a meaningful advance for the field. We also expected and always concern ourselves with the concept of a placebo effect. Anytime you do a study in a placebo-controlled manner, patients perform differently than they might in an otherwise open natural history perspective. Those two aspects were brought into account as we designed and structured this study. While this is an upside scenario, it's something that we hope to be able to demonstrate. It wasn't what we considered necessary. This is gravy on top of the turkey, so to speak. I think that explains why we're seeing it. There's such a much greater difference in placebo versus the clinical improvement that we're seeing on these measures, and that would drive the statistics. Our program was based around that as being kind of the minimal efficacy that would be clinically and important for patients and really a meaningful advance for the field. our program was based around that as being kind of the minimal efficacy that would be clinically and important for patients and really a meaningful advance for the field We also expected and always concern ourselves with the concept of a placebo effect. we also expected and always concern ourselves with the concept of a placebo effect Anytime you do a study in a placebo-controlled manner, patients perform differently than they might in an otherwise open natural history perspective. anytime you do a study in a placebo-controlled manner patients perform differently than they might in an otherwise open natural history perspective Those two aspects were brought into account as we designed and structured this study. those two aspects were brought into account as we designed and structured this study While this is an upside scenario, it's something that we hope to be able to demonstrate. while this is an upside scenario it's something that we hope to be able to demonstrate It wasn't what we considered necessary. it wasn't what we considered necessary This is gravy on top of the turkey, so to speak. this is gravy on top of the turkey so to speak I think that explains why we're seeing it. i think that explains why we're seeing it There's such a much greater difference in placebo versus the clinical improvement that we're seeing on these measures, and that would drive the statistics. there's such a much greater difference in placebo versus the clinical improvement that we're seeing on these measures and that would drive the statistics I think the second question was regarding the meaningfulness of these measures, particularly FVC. I think the second question was regarding the meaningfulness of these measures, particularly FVC. i think the second question was regarding the meaningfulness of these measures particularly fvc FVC, forced vital capacity, is a broad tool used in clinical practice across multiple specialties. FVC has been used as an endpoint in a number of different trials, both intrinsic pulmonary diseases as well as in the neuromuscular community. Depending on the different studies, there are different approaches for what would define clinical meaningfulness in a specific disease. The difference we're seeing at 5% is broadly within and above the ranges that people generally consider as intrinsically meaningful in clinical trials and in clinical practice for this disease, and in clinical practice in general use in specific for this disease. The third question, I can't remember. FVC, forced vital capacity, is a broad tool used in clinical practice across multiple specialties. fvc forced vital capacity is a broad tool used in clinical practice across multiple specialties FVC has been used as an endpoint in a number of different trials, both intrinsic pulmonary diseases as well as in the neuromuscular community. fvc has been used as an endpoint in a number of different trials both intrinsic pulmonary diseases as well as in the neuromuscular community Depending on the different studies, there are different approaches for what would define clinical meaningfulness in a specific disease. depending on the different studies there are different approaches for what would define clinical meaningfulness in a specific disease The difference we're seeing at 5% is broadly within and above the ranges that people generally consider as intrinsically meaningful in clinical trials and in clinical practice for this disease, and in clinical practice in general use in specific for this disease. the difference we're seeing at 5% is broadly within and above the ranges that people generally consider as intrinsically meaningful in clinical trials and in clinical practice for this disease and in clinical practice in general use in specific for this disease The third question, I can't remember. the third question i can't remember

Speaker 14: The third question was about the ability to continue treating people in the study and the placebo arm. I think on that question, Tyler, I think it's a good question. Obviously, with the strength of this data and the clean safety profile, it's something that we're going to have to align with the FDA on before we can make any, you know, on the optimal path forward before we make any changes. The third question was about the ability to continue treating people in the study and the placebo arm. the third question was about the ability to continue treating people in the study and the placebo arm I think on that question, Tyler, I think it's a good question. i think on that question tyler i think it's a good question Obviously, with the strength of this data and the clean safety profile, it's something that we're going to have to align with the FDA on before we can make any, you know, on the optimal path forward before we make any changes. obviously with the strength of this data and the clean safety profile it's something that we're going to have to align with the fda on before we can make any you know on the optimal path forward before we make any changes

Speaker 16: Your next question comes from the line of Salim Syed with Mizuho. Please go ahead. Your next question comes from the line of Salim Syed with Mizuho. your next question comes from the line of salim syed with mizuho Please go ahead. please go ahead

Speaker 13: Hey, congrats, guys. Thanks for the question. If you don't mind, I'll also ask three questions. I guess the first one here is just on the different subgroups you guys had in this trial, the L276I homozygous patients versus the other FKRP genotypes. Can you maybe just articulate if there was any difference between the two groups, or if you saw more or less benefit in one versus the other? Then just a clarification just on the N that was in the different clinical endpoints here. I think you had like 49 on one, 46. This is all for the drug arm, 40 for like 100 m time test, 35 on forced vital capacity. Can you maybe just clarify why the different N on the different clinical measures at 12 months? Lastly, if you think this mechanism could be used in other LGMD subtypes. Thanks. Hey, congrats, guys. hey congrats guys Thanks for the question. thanks for the question If you don't mind, I'll also ask three questions. if you don't mind i'll also ask three questions I guess the first one here is just on the different subgroups you guys had in this trial, the L276I homozygous patients versus the other FKRP genotypes. i guess the first one here is just on the different subgroups you guys had in this trial the l276i homozygous patients versus the other fkrp genotypes Can you maybe just articulate if there was any difference between the two groups, or if you saw more or less benefit in one versus the other? can you maybe just articulate if there was any difference between the two groups or if you saw more or less benefit in one versus the other Then just a clarification just on the N that was in the different clinical endpoints here. then just a clarification just on the n that was in the different clinical endpoints here I think you had like 49 on one, 46. i think you had like 49 on one 46 This is all for the drug arm, 40 for like 100 m time test, 35 on forced vital capacity. this is all for the drug arm 40 for like 100 m time test 35 on forced vital capacity Can you maybe just clarify why the different N on the different clinical measures at 12 months? can you maybe just clarify why the different n on the different clinical measures at 12 months Lastly, if you think this mechanism could be used in other LGMD subtypes. lastly if you think this mechanism could be used in other lgmd subtypes Thanks. thanks

Speaker 14: Okay. Thanks, Salim. Uma, you want to take the first part of that question? Okay. okay Thanks, Salim. thanks salim Uma, you want to take the first part of that question? uma you want to take the first part of that question

Speaker 12: Sure. As you could see when Doug showed the study design, we had a very broad enrollment criteria for the phase three trial. It included both the homozygous L276I patients, and that's about 75% of the study population representing what we see in real-world evidence. The other 25% were the heterozygous and the other FKRP genotypes. We have seen very robust and highly statistically significant results in both of these genotype segments. This is quite consistent with BBP-418 to be a disease-modifying therapy, an oral disease-modifying therapy with a potentially very broad inclusive label. As you can tell, this data is very new to us, so we're analyzing all subgroups and getting clarity on what the data means. Again, very, very promising, highly statistically significant data. Additional details as they emerge, we're going to be presenting it in future medical meetings. Sure. sure As you could see when Doug showed the study design, we had a very broad enrollment criteria for the phase three trial. as you could see when doug showed the study design we had a very broad enrollment criteria for the phase three trial It included both the homozygous L276I patients, and that's about 75% of the study population representing what we see in real-world evidence. it included both the homozygous l276i patients and that's about 75% of the study population representing what we see in real-world evidence The other 25% were the heterozygous and the other FKRP genotypes. the other 25% were the heterozygous and the other fkrp genotypes We have seen very robust and highly statistically significant results in both of these genotype segments. we have seen very robust and highly statistically significant results in both of these genotype segments This is quite consistent with BBP-418 to be a disease-modifying therapy, an oral disease-modifying therapy with a potentially very broad inclusive label. this is quite consistent with bbp-418 to be a disease-modifying therapy an oral disease-modifying therapy with a potentially very broad inclusive label As you can tell, this data is very new to us, so we're analyzing all subgroups and getting clarity on what the data means. as you can tell this data is very new to us so we're analyzing all subgroups and getting clarity on what the data means Again, very, very promising, highly statistically significant data. again very very promising highly statistically significant data Additional details as they emerge, we're going to be presenting it in future medical meetings. additional details as they emerge we're going to be presenting it in future medical meetings I'll turn it over to Doug to answer the question. I'll turn it over to Doug to answer the question. i'll turn it over to doug to answer the question

Speaker 3: The second question was why do we see different Ns on some of the different endpoints? The quick answer for that is that the data incorporates the available data. In the case of the 100 m time test, there are some individuals who are unable to perform the test and are therefore not incorporated into the analysis. For forced vital capacity, our collaborators applied a rigorous standard to ensure validity of the test and the assessments. There were certain patients who were excluded based on their inability to perform the test correctly. This is incorporated into the test statistic, and the test statistic that we are reporting is a conservative adjustment to reflect that. The second question was why do we see different Ns on some of the different endpoints? the second question was why do we see different ns on some of the different endpoints The quick answer for that is that the data incorporates the available data. the quick answer for that is that the data incorporates the available data In the case of the 100 m time test, there are some individuals who are unable to perform the test and are therefore not incorporated into the analysis. in the case of the 100 m time test there are some individuals who are unable to perform the test and are therefore not incorporated into the analysis For forced vital capacity, our collaborators applied a rigorous standard to ensure validity of the test and the assessments. for forced vital capacity our collaborators applied a rigorous standard to ensure validity of the test and the assessments There were certain patients who were excluded based on their inability to perform the test correctly. there were certain patients who were excluded based on their inability to perform the test correctly This is incorporated into the test statistic, and the test statistic that we are reporting is a conservative adjustment to reflect that. this is incorporated into the test statistic and the test statistic that we are reporting is a conservative adjustment to reflect that

Speaker 14: Yeah. The other part about it, Salim, is just the enrollment rate. For example, the primary endpoint of glycosylated alpha-dystroglycan at three months looks at all the patients available at three months, but then, of course, not all of them made it to the 12-month time point at the same time to collect those data. I think your last question was about the applicability of 418 in other LGMDs. We do believe that it could be applicable for LGMD2M and 2U in the US and Europe. These are a little bit smaller conditions than 2I. In Japan, it may have potential in Tokiyama. That's a muscular dystrophy that is actually kind of a found mutation in Japan. It's specific to Japan, but actually the second most common form of muscular dystrophy in Japan. Those are probably the most likely mutation expansion opportunities for 418 specifically. Yeah. yeah The other part about it, Salim, is just the enrollment rate. the other part about it salim is just the enrollment rate For example, the primary endpoint of glycosylated alpha-dystroglycan at three months looks at all the patients available at three months, but then, of course, not all of them made it to the 12-month time point at the same time to collect those data. for example the primary endpoint of glycosylated alpha-dystroglycan at three months looks at all the patients available at three months but then of course not all of them made it to the 12-month time point at the same time to collect those data I think your last question was about the applicability of 418 in other LGMDs. i think your last question was about the applicability of 418 in other lgmds We do believe that it could be applicable for LGMD2M and 2U in the US and Europe. we do believe that it could be applicable for lgmd2m and 2u in the us and europe These are a little bit smaller conditions than 2I. these are a little bit smaller conditions than 2i In Japan, it may have potential in Tokiyama. in japan it may have potential in tokiyama That's a muscular dystrophy that is actually kind of a found mutation in Japan. that's a muscular dystrophy that is actually kind of a found mutation in japan It's specific to Japan, but actually the second most common form of muscular dystrophy in Japan. it's specific to japan but actually the second most common form of muscular dystrophy in japan Those are probably the most likely mutation expansion opportunities for 418 specifically. those are probably the most likely mutation expansion opportunities for 418 specifically

Speaker 16: Your next question comes from the line of Corey Kasimov with Evercore ISI. Please go ahead. Your next question comes from the line of Corey Kasimov with Evercore ISI. your next question comes from the line of corey kasimov with evercore isi Please go ahead. please go ahead

Speaker 5: Hey, good morning, guys. Thank you for taking my question and great to see such strong data. I wanted to ask more about the commercial opportunity. I'm curious, at this point, what percentage of patients are diagnosed today, both in if you can split it between like in the US and globally? From a strategic standpoint, do you plan to commercialize 418 yourself outside of the US, or would you look to out-license the molecule? Thank you. Hey, good morning, guys. hey good morning guys Thank you for taking my question and great to see such strong data. thank you for taking my question and great to see such strong data I wanted to ask more about the commercial opportunity. i wanted to ask more about the commercial opportunity I'm curious, at this point, what percentage of patients are diagnosed today, both in if you can split it between like in the US and globally? i'm curious at this point what percentage of patients are diagnosed today both in if you can split it between like in the us and globally From a strategic standpoint, do you plan to commercialize 418 yourself outside of the US, or would you look to out-license the molecule? from a strategic standpoint do you plan to commercialize 418 yourself outside of the us or would you look to out-license the molecule Thank you. thank you

Speaker 14: Thanks. I'm going to turn it over to Matt. Thanks. thanks I'm going to turn it over to Matt. i'm going to turn it over to matt

Speaker 15: Hi, Corey. Thanks for the question. First, we plan to launch ourselves globally, and we've been preparing in anticipation of positive data. Those assumptions that we put into that include about 7,000 patients between the U.S. and Europe, and about 2,000-2,500 of those are in the U.S. Just to give a little bit of color on some of the commercial parameters that we're looking at, we'll start to refine our pricing assumptions, things like that. As you're thinking about what to expect, I would expect sort of normal rare disease pricing similar to other recent rare disease launches. We'll be using the current infrastructure that we have to kind of put all this together. It should be another blockbuster drug for BridgeBio Pharma. Hi, Corey. hi corey Thanks for the question. thanks for the question First, we plan to launch ourselves globally, and we've been preparing in anticipation of positive data. first we plan to launch ourselves globally and we've been preparing in anticipation of positive data Those assumptions that we put into that include about 7,000 patients between the U.S. and Europe, and about 2,000- 2,500 of those are in the U.S. those assumptions that we put into that include about 7,000 patients between the u.s and europe and about 2,000- 2,500 of those are in the u.s Just to give a little bit of color on some of the commercial parameters that we're looking at, we'll start to refine our pricing assumptions, things like that. just to give a little bit of color on some of the commercial parameters that we're looking at we'll start to refine our pricing assumptions things like that As you're thinking about what to expect, I would expect sort of normal rare disease pricing similar to other recent rare disease launches. as you're thinking about what to expect i would expect sort of normal rare disease pricing similar to other recent rare disease launches We'll be using the current infrastructure that we have to kind of put all this together. we'll be using the current infrastructure that we have to kind of put all this together It should be another blockbuster drug for BridgeBio Pharma. it should be another blockbuster drug for bridgebio pharma

Speaker 14: Yeah. I think I would add just on the diagnosis rates, it's a little TBD right now since there's nothing available for these patients right now. There's no therapies. We must be the first to market for, you know, disease-modifying therapy. I will say I think there's some tailwinds already that exist in the market. There is sponsored genetic testing that's available, for example. I guess, you know, anecdotally, our experience with the clinical trial enrollment may suggest that there's actually kind of maybe more patients identified than we thought. I mean, with the clinical trial enrollment, we enrolled it eight months faster than expected and 20% more patients than expected. The demand for treatment and to be in a study there, again, suggests that there might already be a large volume of patients identified. Yeah. yeah I think I would add just on the diagnosis rates, it's a little TBD right now since there's nothing available for these patients right now. i think i would add just on the diagnosis rates it's a little tbd right now since there's nothing available for these patients right now There's no therapies. there's no therapies We must be the first to market for, you know, disease-modifying therapy. we must be the first to market for you know disease-modifying therapy I will say I think there's some tailwinds already that exist in the market. i will say i think there's some tailwinds already that exist in the market There is sponsored genetic testing that's available, for example. there is sponsored genetic testing that's available for example I guess, you know, anecdotally, our experience with the clinical trial enrollment may suggest that there's actually kind of maybe more patients identified than we thought. i guess you know anecdotally our experience with the clinical trial enrollment may suggest that there's actually kind of maybe more patients identified than we thought I mean, with the clinical trial enrollment, we enrolled it eight months faster than expected and 20% more patients than expected. i mean with the clinical trial enrollment we enrolled it eight months faster than expected and 20% more patients than expected The demand for treatment and to be in a study there, again, suggests that there might already be a large volume of patients identified. the demand for treatment and to be in a study there again suggests that there might already be a large volume of patients identified

Speaker 16: Your next question comes from the line of Mani Foroohar with Leerink Partners. Please go ahead. Your next question comes from the line of Mani Foroohar with Leerink Partners. your next question comes from the line of mani foroohar with leerink partners Please go ahead. please go ahead

Speaker 11: Hey, guys. I'd like to add my congratulations on the data. I have a quick question about correlation between glycosylated alpha-dystroglycan and the various functional measures. Can you share with us to what extent we could get a little bit of a sense of the correlation between one and the other, recognizing you're limited to what you've already disclosed? Where might we look to see a more sort of detailed disclosure of how the one correlates with the other? Hey, guys. hey guys I'd like to add my congratulations on the data. i'd like to add my congratulations on the data I have a quick question about correlation between glycosylated alpha-dystroglycan and the various functional measures. i have a quick question about correlation between glycosylated alpha-dystroglycan and the various functional measures Can you share with us to what extent we could get a little bit of a sense of the correlation between one and the other, recognizing you're limited to what you've already disclosed? can you share with us to what extent we could get a little bit of a sense of the correlation between one and the other recognizing you're limited to what you've already disclosed Where might we look to see a more sort of detailed disclosure of how the one correlates with the other? where might we look to see a more sort of detailed disclosure of how the one correlates with the other

Speaker 14: Yeah. Thanks, Manny. That is going to be part of the ongoing analysis. This is really only that top-line data. We're going to use that data to have a discussion with the FDA, and we'll present a fuller data package most likely at the NDA in March. Yeah. yeah Thanks, Manny. thanks manny That is going to be part of the ongoing analysis. that is going to be part of the ongoing analysis This is really only that top-line data. this is really only that top-line data We're going to use that data to have a discussion with the FDA, and we'll present a fuller data package most likely at the NDA in March. we're going to use that data to have a discussion with the fda and we'll present a fuller data package most likely at the nda in march

Speaker 16: Your next question comes from the line of Josh Schimmer with Cantor. Please go ahead. Your next question comes from the line of Josh Schimmer with Cantor. your next question comes from the line of josh schimmer with cantor Please go ahead. please go ahead

Speaker 9: Hey, congrats on the data, and thanks for taking the questions. Maybe just clarifying for the U.S. patient population, you'd said 2,000-2,500 patients. Are those all identified? How did you kind of come up with that estimate, especially because you suggested it potentially could be higher? Thank you. Hey, congrats on the data, and thanks for taking the questions. hey congrats on the data and thanks for taking the questions Maybe just clarifying for the U.S. patient population, you'd said 2,000- 2,500 patients. maybe just clarifying for the u.s patient population you'd said 2,000- 2,500 patients Are those all identified? are those all identified How did you kind of come up with that estimate, especially because you suggested it potentially could be higher? how did you kind of come up with that estimate especially because you suggested it potentially could be higher Thank you. thank you

Speaker 14: Right. The question was about just how we came up with our patient number estimates. I think that's the question. The estimates are derived from basically the prevalence in the Northern European population. This is a disease that has a founding mutation in Northern Europeans, so the prevalence is much higher in Northern European countries and places where Northern Europeans immigrated to. If you take those prevalence rates and extrapolate them out to the broader population, that's what we've come up with for our patient population. Right. right The question was about just how we came up with our patient number estimates. the question was about just how we came up with our patient number estimates I think that's the question. i think that's the question The estimates are derived from basically the prevalence in the Northern European population. the estimates are derived from basically the prevalence in the northern european population This is a disease that has a founding mutation in Northern Europeans, so the prevalence is much higher in Northern European countries and places where Northern Europeans immigrated to. this is a disease that has a founding mutation in northern europeans so the prevalence is much higher in northern european countries and places where northern europeans immigrated to If you take those prevalence rates and extrapolate them out to the broader population, that's what we've come up with for our patient population. if you take those prevalence rates and extrapolate them out to the broader population that's what we've come up with for our patient population

Speaker 16: Your next question comes from the line of Biren Amin with Piper Sandler. Please go ahead. Your next question comes from the line of Biren Amin with Piper Sandler. your next question comes from the line of biren amin with piper sandler Please go ahead. please go ahead

Speaker 17: Yeah. Hi, guys. Thanks for taking my questions and congrats on the data. I guess, you know, given the strength of the results on the clinical functional endpoint, and you talk about NDA filing in first half 2026, do you still plan to pursue the accelerated approval pathway, or is there a path to full approval? Maybe second question on, you know, a path for ex-US approval. Would you pursue approval prior to readout of the full analysis? I guess, you know, third question is, when can we expect the final full analysis from the trial? Yeah. yeah Hi, guys. hi guys Thanks for taking my questions and congrats on the data. thanks for taking my questions and congrats on the data I guess, you know, given the strength of the results on the clinical functional endpoint, and you talk about NDA filing in first half 2026, do you still plan to pursue the accelerated approval pathway, or is there a path to full approval? i guess you know given the strength of the results on the clinical functional endpoint and you talk about nda filing in first half 2026 do you still plan to pursue the accelerated approval pathway or is there a path to full approval Maybe second question on, you know, a path for ex-US approval. maybe second question on you know a path for ex-us approval Would you pursue approval prior to readout of the full analysis? would you pursue approval prior to readout of the full analysis I guess, you know, third question is, when can we expect the final full analysis from the trial? i guess you know third question is when can we expect the final full analysis from the trial

Speaker 14: Yeah. Thanks for the question. I think it's a good question. Obviously, given the strength of the data, the improvement on the functional endpoints, and the clean safety profile, it is the key question that we want to align with on the FDA about whether to seek an accelerated approval, which is our original strategy, or if this data, as we think, supports a full approval in the U.S. In Europe, we are also going to align with the European regulatory agencies on a path forward there. I think the key principle for us is, given the strength of this data, how do we accelerate access for patients as quickly as possible? Yeah. yeah Thanks for the question. thanks for the question I think it's a good question. i think it's a good question Obviously, given the strength of the data, the improvement on the functional endpoints, and the clean safety profile, it is the key question that we want to align with on the FDA about whether to seek an accelerated approval, which is our original strategy, or if this data, as we think, supports a full approval in the U.S. obviously given the strength of the data the improvement on the functional endpoints and the clean safety profile it is the key question that we want to align with on the fda about whether to seek an accelerated approval which is our original strategy or if this data as we think supports a full approval in the u.s In Europe, we are also going to align with the European regulatory agencies on a path forward there. in europe we are also going to align with the european regulatory agencies on a path forward there I think the key principle for us is, given the strength of this data, how do we accelerate access for patients as quickly as possible? i think the key principle for us is given the strength of this data how do we accelerate access for patients as quickly as possible

Speaker 16: Your next question comes from the line of Andrew Tsai with Jefferies. Please go ahead. Your next question comes from the line of Andrew Tsai with Jefferies. your next question comes from the line of andrew tsai with jefferies Please go ahead. please go ahead

Speaker 4: Hey, good morning. Thanks for taking my question. Congrats also on the compelling data set. Aside from the FDA meeting that you have, what gating items, if there are any, are still outstanding before you can file the NDA? Do you need to run any other peripheral studies in the meantime, or do you even have enough drug for a commercial launch? Secondly, does it make sense to file for breakthrough designation? Thank you. Hey, good morning. hey good morning Thanks for taking my question. thanks for taking my question Congrats also on the compelling data set. congrats also on the compelling data set Aside from the FDA meeting that you have, what gating items, if there are any, are still outstanding before you can file the NDA? aside from the fda meeting that you have what gating items if there are any are still outstanding before you can file the nda Do you need to run any other peripheral studies in the meantime, or do you even have enough drug for a commercial launch? do you need to run any other peripheral studies in the meantime or do you even have enough drug for a commercial launch Secondly, does it make sense to file for breakthrough designation? secondly does it make sense to file for breakthrough designation Thank you. thank you

Speaker 14: Yeah. The gating item really is this alignment with the FDA on whether we're seeking accelerated approval or whether we're seeking traditional approval. You know, we don't anticipate that that's going to affect our timelines. We still anticipate filing our NDA in the first half of next year. We already have priority review. We also have the rare pediatric designation on this program as well. At this point, I don't think that filing for breakthrough is going to give us any additional benefit. Yeah. yeah The gating item really is this alignment with the FDA on whether we're seeking accelerated approval or whether we're seeking traditional approval. the gating item really is this alignment with the fda on whether we're seeking accelerated approval or whether we're seeking traditional approval You know, we don't anticipate that that's going to affect our timelines. you know we don't anticipate that that's going to affect our timelines We still anticipate filing our NDA in the first half of next year. we still anticipate filing our nda in the first half of next year We already have priority review. we already have priority review We also have the rare pediatric designation on this program as well. we also have the rare pediatric designation on this program as well At this point, I don't think that filing for breakthrough is going to give us any additional benefit. at this point i don't think that filing for breakthrough is going to give us any additional benefit

Speaker 16: Your next question comes from the line of Danielle Brill with Truist. Please go ahead. Your next question comes from the line of Danielle Brill with Truist. your next question comes from the line of danielle brill with truist Please go ahead. please go ahead

Speaker 7: Hi, guys. Good morning. Thanks so much for the question and congrats on the excellent data. I have a few questions. First, I'm just curious, maybe you can walk us through how you selected the 100-meter time test and forced vital capacity as the functional endpoint measures for the 12-month analysis. Is there something specific about these that would make them more sensitive to a change after 12 months than, say, NSAID or a 10 m walk test? Were the changes observed in the placebo arm on 100 m time test and serum creatine kinase levels also consistent with natural history? Maybe just a clarification. In your prior conversations with the agency, were they generally supportive of a potential full approval filing with 12 month data that showed significant improvements on functional benefits? Thank you. Hi, guys. hi guys Good morning. good morning Thanks so much for the question and congrats on the excellent data. thanks so much for the question and congrats on the excellent data I have a few questions. i have a few questions First, I'm just curious, maybe you can walk us through how you selected the 100-meter time test and forced vital capacity as the functional endpoint measures for the 12-month analysis. first i'm just curious maybe you can walk us through how you selected the 100-meter time test and forced vital capacity as the functional endpoint measures for the 12-month analysis Is there something specific about these that would make them more sensitive to a change after 12 months than, say, NSAID or a 10 m walk test? is there something specific about these that would make them more sensitive to a change after 12 months than say nsaid or a 10 m walk test Were the changes observed in the placebo arm on 100 m time test and serum creatine kinase levels also consistent with natural history? were the changes observed in the placebo arm on 100 m time test and serum creatine kinase levels also consistent with natural history Maybe just a clarification. maybe just a clarification In your prior conversations with the agency, were they generally supportive of a potential full approval filing with 12 month data that showed significant improvements on functional benefits? in your prior conversations with the agency were they generally supportive of a potential full approval filing with 12 month data that showed significant improvements on functional benefits Thank you. thank you

Speaker 14: Thanks for the question. Doug, do you want to take the clinical question? Thanks for the question. thanks for the question Doug, do you want to take the clinical question? doug do you want to take the clinical question

Speaker 3: I'll take the clinical questions, and then I'll kick it back to Christine for the regulatory question. The first question is why those endpoints and how is that different from the other potential endpoints that you might excel? We selected specifically the 100 m time test and FVC because of the expectation that these were two endpoints that would be likely to be able to show relatively early association and improvement with following administration of the therapy. The 100 m time test is the, I would call it the modern version of the six-minute walk test, the measure of ambulatory function and fatigue that is highly sensitive to changes in function and ability that shows a better ability to differentiate decline in higher functioning patients than the 10 m walk test. We felt that this is a more sensitive scale than the other ambulatory measure. I'll take the clinical questions, and then I'll kick it back to Christine for the regulatory question. i'll take the clinical questions and then i'll kick it back to christine for the regulatory question The first question is why those endpoints and how is that different from the other potential endpoints that you might excel? the first question is why those endpoints and how is that different from the other potential endpoints that you might excel We selected specifically the 100 m time test and FVC because of the expectation that these were two endpoints that would be likely to be able to show relatively early association and improvement with following administration of the therapy. we selected specifically the 100 m time test and fvc because of the expectation that these were two endpoints that would be likely to be able to show relatively early association and improvement with following administration of the therapy The 100 m time test is the, I would call it the modern version of the six-minute walk test, the measure of ambulatory function and fatigue that is highly sensitive to changes in function and ability that shows a better ability to differentiate decline in higher functioning patients than the 10 m walk test. the 100 m time test is the i would call it the modern version of the six-minute walk test the measure of ambulatory function and fatigue that is highly sensitive to changes in function and ability that shows a better ability to differentiate decline in higher functioning patients than the 10 m walk test We felt that this is a more sensitive scale than the other ambulatory measure. we felt that this is a more sensitive scale than the other ambulatory measure FVC has been well established by the history of the disease to show pretty outsized decline. The 2% decline that we see in the placebo arm mirrors what we see in the published natural histories, and that's a pretty stark year-upon-year-upon-year decline. This was specifically chosen because of the decline that we expected to see in the untreated patient. What we're demonstrating today, though, is not just an avoidance of that decline, but a pretty marked improvement in the overall function in those two measures. With regard to the regulatory question. FVC has been well established by the history of the disease to show pretty outsized decline. fvc has been well established by the history of the disease to show pretty outsized decline The 2% decline that we see in the placebo arm mirrors what we see in the published natural histories, and that's a pretty stark year-upon-year-upon-year decline. the 2% decline that we see in the placebo arm mirrors what we see in the published natural histories and that's a pretty stark year-upon-year-upon-year decline This was specifically chosen because of the decline that we expected to see in the untreated patient. this was specifically chosen because of the decline that we expected to see in the untreated patient What we're demonstrating today, though, is not just an avoidance of that decline, but a pretty marked improvement in the overall function in those two measures. what we're demonstrating today though is not just an avoidance of that decline but a pretty marked improvement in the overall function in those two measures With regard to the regulatory question. with regard to the regulatory question

Speaker 14: Yeah. I'll take the regulatory question. Maybe just to back up, the way we designed the study was really in alignment with the FDA, which is the primary endpoint was the North Star endpoint at 36 months. That was the endpoint that the FDA strongly encouraged us to use for approval. Given that, you know, that incident is a relatively insensitive one, takes a long time to show treatment benefit, that's why we wound up with the study with the interim analysis at 12 months where the primary endpoint was based on glycosylated alpha-dystroglycan. The strategy was to seek accelerated approval based on the biomarkers, based on the fact that they are the cause of this disease, and we're targeting the disease at its source and directly impacting glycosylated alpha-dystroglycan. Yeah. yeah I'll take the regulatory question. i'll take the regulatory question Maybe just to back up, the way we designed the study was really in alignment with the FDA, which is the primary endpoint was the North Star endpoint at 36 months. maybe just to back up the way we designed the study was really in alignment with the fda which is the primary endpoint was the north star endpoint at 36 months That was the endpoint that the FDA strongly encouraged us to use for approval. that was the endpoint that the fda strongly encouraged us to use for approval Given that, you know, that incident is a relatively insensitive one, takes a long time to show treatment benefit, that's why we wound up with the study with the interim analysis at 12 months where the primary endpoint was based on glycosylated alpha-dystroglycan. given that you know that incident is a relatively insensitive one takes a long time to show treatment benefit that's why we wound up with the study with the interim analysis at 12 months where the primary endpoint was based on glycosylated alpha-dystroglycan The strategy was to seek accelerated approval based on the biomarkers, based on the fact that they are the cause of this disease, and we're targeting the disease at its source and directly impacting glycosylated alpha-dystroglycan. the strategy was to seek accelerated approval based on the biomarkers based on the fact that they are the cause of this disease and we're targeting the disease at its source and directly impacting glycosylated alpha-dystroglycan Our prior discussions with the FDA have all been about accelerated approval on, and the, I guess, the potential to use glycosylated alpha-dystroglycan as the surrogate. We weren't really expecting statistical significance on the functional improvement at 12 months, and that really wasn't, you know, the tenor of our prior discussion. Given that we have seen highly statistical significant functional improvement, as well as a clean safety profile, which we did expect, I think that's where we want to reopen discussions with the FDA. Our prior discussions with the FDA have all been about accelerated approval on, and the, I guess, the potential to use glycosylated alpha-dystroglycan as the surrogate. our prior discussions with the fda have all been about accelerated approval on and the i guess the potential to use glycosylated alpha-dystroglycan as the surrogate We weren't really expecting statistical significance on the functional improvement at 12 months, and that really wasn't, you know, the tenor of our prior discussion. we weren't really expecting statistical significance on the functional improvement at 12 months and that really wasn't you know the tenor of our prior discussion Given that we have seen highly statistical significant functional improvement, as well as a clean safety profile, which we did expect, I think that's where we want to reopen discussions with the FDA. given that we have seen highly statistical significant functional improvement as well as a clean safety profile which we did expect i think that's where we want to reopen discussions with the fda

Speaker 16: Your next question comes from the line of Anupam Rama with JP Morgan. Please go ahead. Your next question comes from the line of Anupam Rama with JP Morgan. your next question comes from the line of anupam rama with jp morgan Please go ahead. please go ahead

Speaker 1: Hey, guys. Thanks so much for taking the question and congrats on the data. Christine, maybe I can follow up on your just prior comment. Anything more you can share on the nature and severity of some of the treatment emergent adverse events you saw in the treated group? Also, can you say anything about the baseline characteristics and the severity of the patients enrolled in the study just to help us further kind of put the efficacy that we're seeing into context? Thanks so much. Hey, guys. hey guys Thanks so much for taking the question and congrats on the data. thanks so much for taking the question and congrats on the data Christine, maybe I can follow up on your just prior comment. christine maybe i can follow up on your just prior comment Anything more you can share on the nature and severity of some of the treatment emergent adverse events you saw in the treated group? anything more you can share on the nature and severity of some of the treatment emergent adverse events you saw in the treated group Also, can you say anything about the baseline characteristics and the severity of the patients enrolled in the study just to help us further kind of put the efficacy that we're seeing into context? also can you say anything about the baseline characteristics and the severity of the patients enrolled in the study just to help us further kind of put the efficacy that we're seeing into context Thanks so much. thanks so much

Speaker 14: Yeah. Thanks for that, Anupum. I think on the treatment emergent events, we aren't sharing a lot of detail right now only because we need to be mindful of the integrity of the ongoing study before we have the discussions with the FDA. What we've said, of course, is that there are no new ones that we've identified and that the safety profile is very consistent with phase two. I don't know, Doug, if you want to add any more color to that in terms of what we've hoped to discuss about. Yeah. yeah Thanks for that, Anupum. thanks for that anupum I think on the treatment emergent events, we aren't sharing a lot of detail right now only because we need to be mindful of the integrity of the ongoing study before we have the discussions with the FDA. i think on the treatment emergent events we aren't sharing a lot of detail right now only because we need to be mindful of the integrity of the ongoing study before we have the discussions with the fda What we've said, of course, is that there are no new ones that we've identified and that the safety profile is very consistent with phase two. what we've said of course is that there are no new ones that we've identified and that the safety profile is very consistent with phase two I don't know, Doug, if you want to add any more color to that in terms of what we've hoped to discuss about. i don't know doug if you want to add any more color to that in terms of what we've hoped to discuss about

Speaker 3: It's unfortunately a tricky question because the numbers are very low, and we want to avoid further impacting study integrity. There were no new TEAEs, certainly nothing associated with therapy. The safety and risk profile has not changed from what we've described previously. It's unfortunately a tricky question because the numbers are very low, and we want to avoid further impacting study integrity. it's unfortunately a tricky question because the numbers are very low and we want to avoid further impacting study integrity There were no new TEAEs, certainly nothing associated with therapy. there were no new teaes certainly nothing associated with therapy The safety and risk profile has not changed from what we've described previously. the safety and risk profile has not changed from what we've described previously

Speaker 14: Yeah. Encouragingly, as you said as well, the attenuation rate was very low, and it was higher in the placebo arm. I think in terms of the baseline characteristics for the phase three, it's very consistent, actually, with our phase two study population. I don't know if that's anything else. Yeah. yeah Encouragingly, as you said as well, the attenuation rate was very low, and it was higher in the placebo arm. encouragingly as you said as well the attenuation rate was very low and it was higher in the placebo arm I think in terms of the baseline characteristics for the phase three, it's very consistent, actually, with our phase two study population. i think in terms of the baseline characteristics for the phase three it's very consistent actually with our phase two study population I don't know if that's anything else. i don't know if that's anything else

Speaker 3: Yeah. I mean, it's a mixed cohort, and we'll be presenting additional, we'll continue to present this in greater details moving forward. There's a mixed cohort of patients with homozygosity for L276I and patients with other FKRP genotypes that roughly matches the general population. The predominance were ambulatory patients because of the structure of this study. There were a sizable cohort of non-ambulatory patients enrolled as well that are incorporated in appropriate analyses, including forced vital capacity. This is a broad study that we believe will provide sufficient coverage for a relatively expansive label. Yeah. yeah i I mean, it's a mixed cohort, and we'll be presenting additional, we'll continue to present this in greater details moving forward. yeah i mean it's a mixed cohort and we'll be presenting additional we'll continue to present this in greater details moving forward There's a mixed cohort of patients with homozygosity for L276I and patients with other FKRP genotypes that roughly matches the general population. there's a mixed cohort of patients with homozygosity for l276i and patients with other fkrp genotypes that roughly matches the general population The predominance were ambulatory patients because of the structure of this study. the predominance were ambulatory patients because of the structure of this study There were a sizable cohort of non-ambulatory patients enrolled as well that are incorporated in appropriate analyses, including forced vital capacity. there were a sizable cohort of non-ambulatory patients enrolled as well that are incorporated in appropriate analyses including forced vital capacity This is a broad study that we believe will provide sufficient coverage for a relatively expansive label. this is a broad study that we believe will provide sufficient coverage for a relatively expansive label

Speaker 16: Your next question comes from the line of Paul Toy with Goldman Sachs. Please go ahead. Your next question comes from the line of Paul Toy with Goldman Sachs. your next question comes from the line of paul toy with goldman sachs Please go ahead. please go ahead

Speaker 6: Hi. Good morning. Congratulations on the data, and thanks for taking our questions. My first question is, can you maybe comment on if the magnitude of benefit was the same in pediatric patients as it was in the adult patients just in the context of the natural history? I think your international enrollment was largely limited to adults, so maybe just some clarity on that would be helpful. My second question is, as sort of a first-in-class for this therapy, do you anticipate a potential FDA adcom might be held for this, just given the novelty of the category and just sort of the unknown treatment options for this particular disease? Thanks for taking our questions, and congrats again on the data. Hi. hi Good morning. good morning Congratulations on the data, and thanks for taking our questions. congratulations on the data and thanks for taking our questions My first question is, can you maybe comment on if the magnitude of benefit was the same in pediatric patients as it was in the adult patients just in the context of the natural history? my first question is can you maybe comment on if the magnitude of benefit was the same in pediatric patients as it was in the adult patients just in the context of the natural history I think your international enrollment was largely limited to adults, so maybe just some clarity on that would be helpful. i think your international enrollment was largely limited to adults so maybe just some clarity on that would be helpful My second question is, as sort of a first-in-class for this therapy, do you anticipate a potential FDA adcom might be held for this, just given the novelty of the category and just sort of the unknown treatment options for this particular disease? my second question is as sort of a first-in-class for this therapy do you anticipate a potential fda adcom might be held for this just given the novelty of the category and just sort of the unknown treatment options for this particular disease Thanks for taking our questions, and congrats again on the data. thanks for taking our questions and congrats again on the data

Speaker 14: Thank you. On the pediatric subgroups, all the subgroup analyses are ongoing, so we'll disclose that at a later time. On the, sorry, what was the second part of the question? Adcom, right. Adcom. Prior to this data, I actually thought an adcom was more likely than not, and now I think it's the opposite. I think given the strength of the data, how robust it is, how consistent it is, how overwhelming and positive it is in the clean safety profile, I'm not really sure that there's, I don't know what we're going to discuss. I think it's less likely now. Thank you. thank you On the pediatric subgroups, all the subgroup analyses are ongoing, so we'll disclose that at a later time. on the pediatric subgroups all the subgroup analyses are ongoing so we'll disclose that at a later time On the, sorry, what was the second part of the question? on the sorry what was the second part of the question Adcom, right. adcom right Adcom. adcom Prior to this data, I actually thought an adcom was more likely than not, and now I think it's the opposite. prior to this data i actually thought an adcom was more likely than not and now i think it's the opposite I think given the strength of the data, how robust it is, how consistent it is, how overwhelming and positive it is in the clean safety profile, I'm not really sure that there's, I don't know what we're going to discuss. i think given the strength of the data how robust it is how consistent it is how overwhelming and positive it is in the clean safety profile i'm not really sure that there's i don't know what we're going to discuss I think it's less likely now. i think it's less likely now

Speaker 16: Your next question comes from the line of Jason Zemansky with Bank of America. Please go ahead. Your next question comes from the line of Jason Zemansky with Bank of America. your next question comes from the line of jason zemansky with bank of america Please go ahead. please go ahead

Speaker 8: Good morning. Congrats on the data, and thanks for squeezing us in. I wanted to ask on your expectations over the long-term outcomes. I mean, granted, things are still early, but it did appear that the alpha-DG levels continued to improve somewhat over the 12 month interval. Is there the potential that longer-term exposure can drive even better responses? Alternatively, is there a limit to how much you can replace and at some level, you know, patients will decline at, you know, albeit a more modest level? Thank you. Good morning. good morning Congrats on the data, and thanks for squeezing us in. congrats on the data and thanks for squeezing us in I wanted to ask on your expectations over the long-term outcomes. i wanted to ask on your expectations over the long-term outcomes I mean, granted, things are still early, but it did appear that the alpha-DG levels continued to improve somewhat over the 12 month interval. i mean granted things are still early but it did appear that the alpha-dg levels continued to improve somewhat over the 12 month interval Is there the potential that longer-term exposure can drive even better responses? is there the potential that longer-term exposure can drive even better responses Alternatively, is there a limit to how much you can replace and at some level, you know, patients will decline at, you know, albeit a more modest level? alternatively is there a limit to how much you can replace and at some level you know patients will decline at you know albeit a more modest level Thank you. thank you

Speaker 14: Yeah, thanks. I'll turn it over to Doug. Yeah, thanks. yeah thanks I'll turn it over to Doug. i'll turn it over to doug

Speaker 3: Yeah. Obviously, we'll need to see ultimately. Our expectation, based on what we've seen from our natural history, from the natural history studies, what we've seen from the longer-term datasets from the University of Iowa, is that patients who are not treated will experience a continued ongoing and inexorable decline along the fashion that we're seeing in our placebo arm, and that will continue in the longer term. We believe that this demonstrates a change in trajectory. You know, the magnitude of that and, you know, the continued directionality obviously will remain to be seen. We expect that that gap and that difference between the treatment and placebo arms will continue to grow with longer and longer therapy. Again, that remains to be demonstrated with the data. Yeah. yeah Obviously, we'll need to see ultimately. obviously we'll need to see ultimately Our expectation, based on what we've seen from our natural history, from the natural history studies, what we've seen from the longer-term datasets from the University of Iowa, is that patients who are not treated will experience a continued ongoing and inexorable decline along the fashion that we're seeing in our placebo arm, and that will continue in the longer term. our expectation based on what we've seen from our natural history from the natural history studies what we've seen from the longer-term datasets from the university of iowa is that patients who are not treated will experience a continued ongoing and inexorable decline along the fashion that we're seeing in our placebo arm and that will continue in the longer term We believe that this demonstrates a change in trajectory. we believe that this demonstrates a change in trajectory You know, the magnitude of that and, you know, the continued directionality obviously will remain to be seen. you know the magnitude of that and you know the continued directionality obviously will remain to be seen We expect that that gap and that difference between the treatment and placebo arms will continue to grow with longer and longer therapy. we expect that that gap and that difference between the treatment and placebo arms will continue to grow with longer and longer therapy Again, that remains to be demonstrated with the data. again that remains to be demonstrated with the data

Speaker 12: One more thing, which is the data that we showed, that's the change from baseline. The one-year time point, we're essentially already doubled the baseline level of glycosylated alpha-DG. About 21%-22% has already increased by 23%. It's a remarkable increase already at 12 months. One more thing, which is the data that we showed, that's the change from baseline. one more thing which is the data that we showed that's the change from baseline The one-year time point, we're essentially already doubled the baseline level of glycosylated alpha-DG. the one-year time point we're essentially already doubled the baseline level of glycosylated alpha-dg About 21%- 22% has already increased by 23%. about 21%- 22% has already increased by 23% It's a remarkable increase already at 12 months. it's a remarkable increase already at 12 months

Speaker 14: Yeah, just with that in context, what we believed was clinically meaningful was an absolute increase of 5%. The fact that we're getting a 17% increase already at three months is pretty meaningful. Yeah, just with that in context, what we believed was clinically meaningful was an absolute increase of 5%. yeah just with that in context what we believed was clinically meaningful was an absolute increase of 5% The fact that we're getting a 17% increase already at three months is pretty meaningful. the fact that we're getting a 17% increase already at three months is pretty meaningful

Speaker 16: That concludes our question and answer session. I will turn the conference back over to Christine Siu for closing comments. That concludes our question and answer session. that concludes our question and answer session I will turn the conference back over to Christine Siu for closing comments. i will turn the conference back over to christine siu for closing comments

Speaker 14: All right. Thanks, everyone. I think, you know, based on the strength of the data, I think we're very excited about the potential here. It just could be very transformative for these patients, for this community, because we could offer really, you know, we could be first to market with an oral disease-modifying therapy. It's a functional improvement. We're excited. Thank you. All right. all right Thanks, everyone. thanks everyone I think, you know, based on the strength of the data, I think we're very excited about the potential here. i think you know based on the strength of the data i think we're very excited about the potential here It just could be very transformative for these patients, for this community, because we could offer really, you know, we could be first to market with an oral disease-modifying therapy. it just could be very transformative for these patients for this community because we could offer really you know we could be first to market with an oral disease-modifying therapy It's a functional improvement. it's a functional improvement We're excited. we're excited Thank you. thank you

Speaker 16: Ladies and gentlemen, that does conclude today's conference call. Thank you for your participation, and you may now disconnect. Ladies and gentlemen, that does conclude today's conference call. ladies and gentlemen that does conclude today's conference call Thank you for your participation, and you may now disconnect. thank you for your participation and you may now disconnect