Good morning, and welcome to Beam Therapeutics conference call. At this time, all participants are in listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is being recorded at Beam's request. I would now like to turn the call over to Holly Manning, Vice President of Investor Relations and External Communications. Thank you, operator. Good morning, everyone, and welcome to Beam's conference call to review top-line clinical data from the phase I/II trial of BEAM- 302 in patients with alpha-1 antitrypsin deficiency. You can access slides for today's call by going to the investor section of our website, beamtx.com. With me on the call today with prepared remarks are John Evans, our Chief Executive Officer, Dr. Amy Simon, our Chief Medical Officer, Dr. Jeff Teckman from Saint Louis University, and Dr. Giuseppe Ciaramella, our president. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our most recent Annual Report on Form 10-K, and any other filings that we may make with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, Beam specifically disclaims any obligation to update or revise any forward-looking statements even if our views change. With that, I will turn the call over to John. Thanks, Holly, and good morning, everyone. At Beam, our vision is to provide lifelong cures for patients suffering from serious diseases. We believe base editing uniquely positions us to fulfill that vision through one-time, durable genetic medicines that correct disease at its root cause while delivering predictable and reproducible outcomes. One year ago, we established clinical proof of concept for our one-time in vivo base edited therapy, BEAM-302 in alpha-1 antitrypsin deficiency, or AATD, and accomplished an incredible milestone for the field of genetic medicine, delivering, to our knowledge, the first ever genetic correction of a disease-causing mutation in DNA. Today, we're excited to share a compelling and robust data set from 29 AATD patients treated with BEAM-302 in the ongoing phase I/II study. These updated data further strengthen our belief in the best-in-class and first-in-class potential of this one-time therapy and paved the way for the advancement of BEAM-302 into pivotal development. Beam was founded on a simple but powerful idea, that making precise single- base changes in DNA could fundamentally change how we treat many serious genetic diseases. Base editing allows us to correct mutations without creating double-strand DNA breaks. Our goal is to translate that capability into one-time genetic medicines that durably and predictably restore normal gene function. We believe that predictability is not just a scientific advantage, it's a strategic one. Predictable outcomes can streamline R&D, reduce development risk, support regulatory efficiency, and ultimately build confidence among physicians, patients, and payers. Over time, we believe that impact can ripple across the entire healthcare ecosystem. That same predictability also allows us to build a scalable platform for developing multiple genetic medicines. Many of the core components of these therapies can be reused across programs so that once we demonstrate success in one setting, we can apply those capabilities to additional diseases with greater efficiency. In that way, we're not simply advancing a single therapy, we're building a repeatable engine for developing multiple genetic medicines over time. Our liver-targeted in vivo portfolio is a clear example of this platform in action, now with three core programs that are in or nearing clinical development. BEAM-302 in AATD, the focus of today's discussion, as well as BEAM-301 for glycogen storage disease 1A, and BEAM-304 for phenylketonuria, all leverage our LNP delivery capabilities, enabling us to apply the same core technologies across multiple programs and move them forward efficiently through emerging regulatory pathways. Today's data further underscores the strength of our industry-leading in vivo liver-targeted precision gene editing technology and our ability to efficiently and rapidly execute to advance to pivotal development for BEAM-302. Before turning the call over to Amy to walk through the results in detail, I'd like to briefly highlight a few key takeaways from the data set we're reporting this morning. First, treatment with BEAM-302 continues to demonstrate robust and durable efficacy with more patients at higher doses and longer follow-up. In the single-dose 60 mg cohort, where patients have follow-up out to 12 months, we observed meaningful increases in both total and functional AAT, achieving steady-state mean levels of 16 μM, and once again with all patients above the 11 μM protective threshold that is associated with lung health. In addition, treatment resulted in substantial reductions of approximately 84% in mutant Z-AAT, the toxic protein responsible for the liver manifestations of the disease, and that in circulation can also contribute to lung disease. Most importantly, these patients now produce corrected M-AAT for the first time. As seen in a clear shift in circulating AAT protein composition to approximately 94% corrected M-AAT, consistent with correction of the underlying genetic mutation. All of these findings are consistent with AAT profiles seen in MZ genotype carriers, people who do not have severe AATD nor progressive disease and are not at elevated risk for lung or liver disease without secondary factors like smoking or obesity. Second, we now have strong evidence that AAT production is inducible following BEAM-302 treatment during periods of inflammation when it is most needed, as expected from BEAM-302's mechanism of action. In one patient, AAT levels increased to approximately 30 μM during a respiratory infection and critically retained the corrected AAT composition of approximately 95% M-AAT, suggesting the edited gene does indeed function under normal physiologic regulation following treatment with BEAM-302. This is the strongest induction result yet observed after a genetic treatment in AATD, showing that treatment with BEAM-302 not only elevates basal AAT levels to a new floor similar to carrier levels, it further provides a dynamic capacity in the body to generate even more AAT whenever it is most needed. Restoring the AAT acute phase response in these treated patients offers a fundamentally different treatment profile from that seen with augmentation therapies and shows the power of precision base editing to correct all aspects of this disease. Third, BEAM-302 continues to demonstrate a well-tolerated safety profile across the single-dose cohorts, with Grade 1 transaminase elevations being the most common adverse event. Based on the strength of both the safety and efficacy data, we have selected 60 mg as the optimal biological dose for our pivotal cohort, which we plan to initiate in the second half of this year. Taken together, we believe these findings reinforce the potential for BEAM-302 as a best-in-class and first-in-class one-time treatment for AATD. With that, I'll turn the call over to Amy to go through these BEAM-302 findings in more detail. Thanks, John. Alpha-1 Antitrypsin Deficiency, or AATD, is a serious genetic disorder caused by mutations in the SERPINA1 gene, which affects the production of alpha-1 antitrypsin, or AAT, a protein made in the liver that is secreted into the bloodstream to protect the lungs from inflammation and damage. The most common and severe form of AATD results from mutations in the Z allele known as PiZ, which is caused by a single G-to-A point mutation in the SERPINA1 gene. This results in the expression of a pathogenic variant of AAT, known as Z-AAT, that misfolds and aggregates in the liver, leading to liver damage and disease such as cirrhosis. You'll hear more about this from Dr. Teckman shortly. The Z-AAT made in the liver is poorly secreted into the circulation and less effective in inhibiting neutrophil elastase, leading to total circulating levels of AAT that are 10%-15% of normal in homozygous PiZZ individuals. As a consequence, the lung is left unprotected from neutrophil elastase and other damaging proteases that can cause progressive lung destruction, resulting in early-onset emphysema. In this disease, it is caused by too much abnormal AAT that gets stuck in the liver and too little AAT that gets out in the circulation. The current standard of care for AATD for patients with lung disease primarily consists of treatment for emphysema, such things as bronchodilators, inhaled steroids, oxygen therapy, and with severe cases requiring lung transplantation. The only approved treatment today, plasma-derived AAT or augmentation therapy, requires weekly intravenous infusions to achieve static levels of AAT, lacking the natural upregulation of AAT so important during infections and inflammatory processes such as respiratory infections. While augmentation has been shown to slow lung disease progression, it does not stop it, nor does it prevent ongoing liver damage and has no impact on the Z-AAT aggregates in the liver or circulation. Treatment for liver disease is limited to supportive care, as there are currently no approved therapies. In severe cases, liver transplantation remains the only option. The PiZZ genotype accounts for over 95% of severe AATD cases, and despite affecting more than 100,000 individuals in the U.S., only about 10% of people living with this disease have been diagnosed. As shown in slide 12, clinical genetics provides critical information on a wide range of AAT levels and highlights why reaching the protective threshold of greater than 11 μM for AAT in circulation is critical for decreasing disease risk related to AATD. Patients with a severe PiZZ genotype have two copies of the disease-causing mutation, leading to a high risk of developing both emphysema and liver disease. These patients have very low levels of AAT between 3 μM-7 μM, shown in orange. All of their AAT is in the mutant Z-AAT form, which is much less effective and can form polymers in circulation, leading to lung inflammation and injury. In the middle are individuals with just one mutant PiZ copy, referred to as MZ or SZ individuals. In this case, the majority of these individuals have AAT levels above 11 μM. On the right-hand side of the slide, you can see how these genotypes correspond to lifetime risk for emphysema and liver disease. People with the PiZZ genotype are greater than 30x more likely to develop emphysema and greater than 20 x more likely to develop liver fibrosis or cirrhosis. Conversely, an SZ or MZ individual's risk is only marginally greater than a person with no mutation, and disease in these individuals requires the presence of additional risk factors such as smoking or obesity. These genotype characteristics are important as they help define what the critical goalposts are for efficacious AAT treatment. Any treatment that can achieve carrier range or better levels of AAT greater than that 11 μM protective threshold, along with further upregulation of the gene during inflammation, would eliminate risk of progressive disease and would represent a functional cure of severe AATD. Our base editor consists of two components, an mRNA encoding an adenine base editor protein and a guide RNA that directs it to the precise location of a Z mutation in the SERPINA1 gene. Both are encapsulated in a lipid nanoparticle, or LNP, for delivery to the liver. Once in the liver cells or hepatocytes, the base editor precisely and directly corrects the misspelling, so it changes the A base into a G base, converting the disease-causing PiZ mutation back to the normal functioning PiM form. By correcting the root cause of AATD at the most proximal source, the DNA, we believe that BEAM-302 has the potential to deliver on the critical aspects of a one-time transformational genetic medicine. First and foremost, our goal with BEAM-302 is to have a person make corrected and properly functioning M-AAT that gets into the circulation so that it is above the protective threshold of 11 μM, which, as described earlier, is informed through genetics and was clinically accepted as the basis of augmentation's approval. Second, BEAM-302 aims to treat the full spectrum of AATD's disease manifestations by significantly reducing mutant Z-AAT levels as much as possible to prevent aggregates in the liver and blood that can lead to ongoing organ damage. Finally, AAT needs to be available in a dynamic manner, meaning that during periods of inflammation or infection, AAT levels need to be able to increase in order to combat lung destruction from unopposed proteases generated from inflammatory cells, such as a neutrophil elastase protease. This is not possible with existing therapies like augmentation. With those goals in mind, we designed a robust phase I/II trial to assess early safety and efficacy of BEAM-302 and enable dose selection in patients across the spectrum of AATD. The dose escalation phase of the study is structured in two parts. Part A includes patients with lung disease to establish an understanding of the safety in patients without clinically evident liver disease, followed by Part B, which includes patients with mild to moderate liver disease with or without AATD-associated lung disease. As of the February 10, 2026 data cutoff, we have treated a total of 29 patients across both Part A and Part B, representing a meaningful update from our proof- of -concept data last year, where we presented data from nine patients. In Part A, we've completed a 15 mg cohort with three patients dosed for 12-18 months of follow-up, a 30 mg cohort with three patients, each with 12 months of follow-up, a 60 mg cohort with six patients followed for five to 12 months, a 75 mg cohort with nine patients followed for two to 9 months, and a multi-dose cohort evaluating two doses of 60 mg given 8 weeks apart, which included three patients followed for 84 days or 28 days after the second dose. In Part B, we completed a 30 mg cohort with three patients followed for four to five months and dosed two patients in a 60 mg cohort. The first patient had three months of follow-up and the second patient was dosed after the February 10 data cut and is included in the safety data throughout the DLT period but excluded from the efficacy data. Turning to safety, single-dose BEAM-302 demonstrated a well-tolerated safety profile at doses up to 75 mg. Importantly, the safety profile was consistent in patients across all single-dose Part A and Part B cohorts. In the 26 patients treated with single-dose BEAM-302 from 15 mg up to 75 mg, no serious adverse events, dose limiting toxicities, or Grade 3 or higher adverse events were observed. All treatment emergent adverse events were mild to moderate. Grade 1 asymptomatic transient elevations in ALT and AST were observed within the first 28 days in some patients. In addition, Grade 1 and Grade 2 infusion-related reactions were observed and all resolved within a day. In the multi-dose cohort evaluating two doses of 60 mg in three patients, we observed a higher rate of events following the second dose of BEAM-302. One patient experienced Grade 4 ALT and Grade 3 AST increases within days of the second dose, which were asymptomatic and resolved without treatment. A Grade 2 ALT increase occurred in another patient, which also resolved without treatment. No clinical signs of liver dysfunction or bilirubin increases were observed in any patient. Transient Grade 2 IRRs occurred in all patients. Turning to efficacy, treatment with BEAM-302 led to durable increases in total AAT into the MZ carrier range at single doses of 60 mg or greater. Here we show steady-state mean total AAT levels by dose, which is the mean of each patient's total AAT levels measured by an LC-MS assay from day 28 to their month 12 visit, or until the patient's last visit if earlier than 12 months. In the 60 mg cohort, where we have now dosed six patients with follow-up out to 12 months, we observed a steady-state total AAT mean of 16.1 μM. In addition, all patients consistently and durably demonstrated mean steady-state total AAT levels above the 11 μM protective threshold. In the 75 mg cohort with nine patients and follow-up out to nine months, we observed a steady-state total AAT mean of 14.4 μM. Increased total AAT in circulation was functional, as demonstrated by a functional AAT assay based on neutrophil elastase inhibition. The fold change from baseline in total AAT was comparable between the 60 mg and 75 mg single-dose cohorts, suggesting near saturation editing at doses greater than or equal to 60 mg. BEAM-302 was designed to increase total AAT by inducing expression of corrected M-AAT, while at the same time stopping the expression of mutant Z-AAT. As shown here, mutant Z-AAT was durably and significantly reduced by 80% at steady state compared to baseline in the highest dose cohorts. As a result, newly produced corrected M-AAT comprised the majority of total AAT in the circulation, with 94% M-AAT in the 60 mg cohort and 91% M-AAT in the 75 mg cohort. This exceeds the AAT profile seen in people with the MZ genotype, who have 80% M-AAT and 20% Z-AAT in circulation and do not have disease unless there is a second injurious insult. Moving to Part B, patients with AAT-related liver disease show similar efficacy trends as Part A patients without liver disease. In the 30 mg Part B cohort, three patients achieved a steady-state mean total AAT of 12.5 micromole, of which 75% was newly produced M-AAT, representing a 51% reduction in mutant Z-AAT. In the 60 mg Part B cohort, only one patient was efficacy evaluable at the time of the data cutoff. That patient achieved a steady-state mean total AAT of 17.2 μM, and similar to the 60 mg Part A cohort, 95% was newly produced M-AAT, driven by an 86% decrease in Z-AAT. In the multi-dose cohort, we observed an efficacy profile consistent with the single-dose 60 mg cohort. The three multi-dose patients achieved a mean of 16.5 μM of total AAT at day 84, which was 28 days following the second dose of 60 mg of BEAM-302. In addition, the mean Z-AAT reduction was 80%, and the newly produced M-AAT was 93% of total AAT. Together, these early data suggest that a single dose of 60 mg BEAM-302 has achieved near saturation editing. As I highlighted earlier, one of the goals of therapy with BEAM-302 is to restore the physiologic control of AAT during inflammation, which is when lungs require higher AAT levels to maintain protection against tissue-damaging proteases. Here we show strong evidence of inducibility of AAT in a patient who experienced a respiratory infection roughly eight months after treatment with BEAM-302. This patient was dosed with 60 mg of BEAM-302 in Part A and achieved steady-state mean total AAT of about 16 μM through month six. At an unscheduled visit around month 8, patient presented with a respiratory infection resulting in an elevated CRP and a concomitant increase in total AAT to approximately 30 μM. After the infection resolved, their total AAT levels trended back down, along with their CRP values by their month nine scheduled visit. Importantly, the patient maintained consistent AAT composition of 94% M-AAT before, during, and after the respiratory infection. This case study shows clearly that there are two distinct aspects of AAT protection offered by BEAM-302 treatment. First, the achievement of a new basal AAT level above the protective threshold achieved within 28 days after treatment. Second, the ability to produce significantly more corrected M-AAT on demand during periods of inflammation or infection. In summary, we are encouraged by these robust and comprehensive BEAM-302 clinical data now in 29 patients and follow-up out to 18 months. These data demonstrate that a single 60 mg dose of BEAM-302 led to durable correction of the PiZ mutation, resulting in increases in total AAT to a mean of 60 μM above the therapeutic threshold of 11 μM and into the MZ range. Production of corrected functional M-AAT in circulation for the first time and significantly decreased mutant Z-AAT by approximately 80%. Treatment with BEAM-302 enabled production of corrected and functional M-AAT that was under normal regulatory control, as shown by the increase in AAT that occurred in response to inflammation in a patient with a respiratory tract infection, enabling the body to naturally regulate AAT as needed. Importantly, BEAM-302 was well-tolerated with an acceptable safety profile at all single doses tested to date in 26 patients. Based on the strength of safety and the efficacy profile of BEAM-302 in single-dose cohorts, 60 mg was chosen as the optimal biological dose for the pivotal trial, which we plan to initiate in the second half of this year. Tino will provide more details about the next steps for pivotal development shortly. Taken together, we believe these data demonstrate the potential for BEAM-302 to be a transformative one-time treatment for AATD that could meaningfully impact both the lung and liver manifestations of the disease. With that, I would like to turn the call over to Dr. Jeffrey Teckman. Dr. Teckman is a professor of pediatrics and biochemistry at Saint Louis University School of Medicine and a recognized world leader in alpha-1 antitrypsin deficiency. His over 30 years of research in clinical care have focused on the mechanisms of liver injury in AATD and on improving the diagnosis and clinical management of patients across the disease spectrum. We're pleased to have him with us today to provide a clinical perspective on the disease, the needs of patients living with AATD today, and how emerging genetic medicines could reshape the way this disease is treated in the future. Dr. Teckman, over to you. Thank you, Amy. It's a pleasure to be here. On a personal note, I've been working on alpha-1 antitrypsin deficiency for a long time. When I first started, we didn't even know how this disease worked in the liver, let alone a concept that we would have, like, cures, on the horizon. It's very exciting to see how much has happened. I think the question, you know, to first start with is, you know, why alpha-1 antitrypsin deficiency now? You know, there are a lot of conditions. There's a lot of interest in biological treatments. You know, why this disease? Well, first of all, there's an increased awareness in the liver disease and hepatology field. There has been a lot of talk about steatotic liver disease, quote-unquote, our new word for fatty liver disease, steatotic liver disease. There's a recognition that metabolic genetic liver disease like alpha-1 antitrypsin deficiency actually cause steatotic liver disease. As more people with steatotic liver disease are being evaluated, there's more testing going on for specific causes like alpha-1 antitrypsin deficiency. The lung disease of alpha-1 is well known, but the patients are not fully diagnosed. The treatment options, while they exist, are suboptimal. There is a protein replacement, as we'll talk about, but it does not return people to wild type. It's very expensive, and it's burdensome to patients. What's also unique about alpha-1 antitrypsin deficiency is the patient community is highly centralized. There is a very active foundation, the Alpha-1 Foundation. They have national meetings, they have a registry, they have a therapeutic development network, and they're a major mover in research and treatment and in lobbying for alpha-1 antitrypsin deficiency. These factors together really make this a great time to be developing treatments for alpha-1. Next slide. Just as background reminder, the alpha-1 gene, the SERPINA1 gene, has hundreds of variants. M being the normal wild type allele, which is MM, is 96%-98% of the population in the United States and Europe. The Z allele is by far responsible for 90%-95% of disease. People sometimes also talk about the S allele, which is an intermediate disease allele, which also when present with Z especially, it can be related to disease. Really the vast majority of diseased individuals are ZZ. Next slide. As you might recall, the liver disease in alpha-1 is a storage disease, and the lung disease is a serum deficiency. That's why it's called alpha-1 antitrypsin deficiency, because it was originally identified as a serum deficiency, but the liver has too much. Next slide. This is just a schematic of alpha-1 protein processing in the liver. On the left side, you see a normal wild-type MM individual. That's the endoplasmic reticulum of the hepatocyte. The little black wavy lines are nascent polypeptide chains of AAT protein, and it folds into its secretion-competent conformation. That's the little knot. And then it's secreted into the blood in huge quantities. The adult liver makes 2 g per day of alpha-1 antitrypsin. On the right side, a ZZ individual is still synthesizing the same number of nascent polypeptides, but they do not fold efficiently into the secretion-competent conformation. Only 15% of the peptides reach a secretion-competent conformation are secreted. The rest accumulate in the ER of the hepatocyte. Now, most of those polypeptides are degraded by proteolysis pathways within the hepatocyte. But for reasons we're not totally sure, some accumulate and form these unusual, what we call polymers of protein, which are highly cytotoxic to the cell. Again, you have the situation where the liver has too much, but the serum has too little. Next slide. These are photomicrographs of human ZZ liver. On the left side is H&E. On the right side is what we call periodic acid-Schiff with digestion or PAS with digestion. The PAS stains glycogen and glycoproteins red purple, and the digestion washes the stain out of glycogen. If you have an accumulation of glycoproteins in the cell, which is shown there by the inclusions and what we call globules, that shows the accumulation. You know, sometimes those are 100% made up of Z protein in the polymerized conformation. Sometimes those accumulations are larger than the nucleus. It really is very toxic to the liver cell. Next slide. What's the risk of liver and lung disease? It is complicated. Let me just walk you through the slide for a second. If you look at the top, and as from left to right is the odds ratio that's shown at the very bottom. And you see the line there on one, you know, that's the same risk as MM individual. At the very top you see MZ, and MZ individuals have a modest 1.7-ish, you know, odds ratio increase of liver disease and cirrhosis. We think of MZ being a genetic modifier of other liver diseases. Most of those people have other kinds of steatotic liver disease, MASH, other things like that. The risk of lung disease in MZ, again, it shows there, you know, is between 1.5 and 2, but really that's just smokers. Non-smokers who are MZ appear to have no increased risk of lung disease. If you look down a little further on FZ, the cirrhosis risk for lifetime for FZ might be an odds ratio of three over MM individuals, so increased. And emphysema again, you know, between 1.5-2. Down at the bottom in ZZ, the risk of fibrosis, cirrhosis lifetime, the odds ratio is more than 20. Significantly increased over the general population. Likewise with emphysema, somewhere between 30-40 odds ratio increase of risk compared to MM individuals. What's really interesting about the data is that, you know, we appear to. In this treatment, you appear to be able to make people at least MZ, if not better. That would eliminate 95% of the risk, which, you know, is incredible, and very exciting and, something that, you know, we're anxious to see, you know, how it turns out with further study. Next slide. This just sort of says over time, over lifetime, because what's interesting also about this disease is it affects different people, different ages differently. On the vertical is the incidence of medically significant disease in a ZZ individual at a certain age. Then you have age, you know, from left, right across the bottom. Early in life, ZZ babies and children can develop liver disease, but it's only about 20% of ZZ individuals have enough disease to come to medical attention in childhood. The risk of liver disease in young adulthood and incidence of liver disease is very low, but it goes up later in adulthood and again becomes significant as a lifelong risk. With regard to lung disease, you do see an increased risk of childhood asthma, but not emphysema in ZZ children. The lung disease really starts to become evident in the thirties and older. The lung function decline in alpha-1 antitrypsin deficiency is greater than the in MM individuals in general population. Now not everyone has, who's ZZ has accelerated lung function decline, but it is well known that it is higher and really even if you're a non-smoker. Next slide. I wanted to go back and touch on how the American Association for the Study of Liver Diseases, AASLD, which is the worldwide leader in liver disease science. Just in the last couple years, we've changed the way we look at "fatty liver disease." It's not just a nomenclature change, but it's really a recognition change. We call steatotic liver disease overall. This again is the official sort of scheme, which not only shows metabolic dysfunction associated steatotic liver disease, so that's individuals with obesity, high lipids, who then, you know, develop MASLD, as well as alcohol. It's also recognized that increasingly monogenic diseases like alpha-1 antitrypsin deficiency, you see in the red circle on the right, contributes to the steatotic liver disease, group of patients. This has really led to an increased focus on diagnosis because it's on clinical grounds to a hepatologist. You just, you know, history, physical exam, basic lab tests. You can't differentiate alpha-1 antitrypsin deficiency from MASLD or alcohol. You really need to test for it specifically. That's being increasingly recognized. Especially as treatments are rolled out, it's gonna be tested for even more. We've seen that in a lot of rare diseases where when there's no treatment, the testing is modest. But when new treatments are available, there's a huge spike in testing. We saw that actually in alpha-1 antitrypsin deficiency in the late 1980s and in the 1990s when the protein replacement for the lung disease became available. There was a dramatic increase in diagnosis. We went from just a few hundred people on replacement therapy to thousands and thousands on replacement therapy in just a decade as a result of more treatment. Next slide. As we said, the liver currently has no approved treatment but supportive care and liver transplant if liver failure becomes untreatable. The lung disease does have the protein replacement, which is an intravenous product. It's fairly burdensome, and it doesn't do anything for the liver, right? Because as I said, the liver is a storage disease and the lung disease is a serum deficiency. You know, this really brings up how that patients are really ready for you know, new treatment options. There would seem to be significant interest among patients on IV replacement therapy to move to something more permanent such as you know, a DNA-targeted treatment which would be equal, if not better, to the protein replacement. I think one of the key concepts which has been touched on is that alpha-1 antitrypsin protein is an acute phase reactant, so it can increase three to five -fold in serum with inflammation. That seems to be very important in the pathology, pathophysiology of preventing damage, because if you get inflammation of the lung and pneumonia, then you make a lot more alpha-1 antitrypsin to protect the host tissues from injury. That's part of the normal physiology. People on IV protein replacement don't infuse more when they're sick. They just have that same dose, so they don't get that boost. We see that in some of the data that there is an acute phase reactant boost, which will, you know, probably be much more effective at protecting the lung and not require weekly infusion. There's a lot of interest in patients, you know, for this kind of intervention. Next slide. Again, just touching on the community, the Alpha-1 Foundation, their registry, their therapy development network, their funding of research, and their support with government. I personally have been to the FDA a number of times as part of delegations from the Alpha-1 Foundation to discuss therapeutic development, to discuss how these treatments should be evaluated, and how important it is to treat both the liver and the lung. These are very exciting developments. I think the community is going be very excited about the data that, you know, we've been discussing. I think we're very excited to see not only improved treatment, but cures for this disease. Next slide. Again, in summarizing our key takeaways, alpha-1 antitrypsin deficiency has a wide range of presentations over a full lifetime, from infantile liver disease to emphysema in older adults. It's way underdiagnosed but increasingly being recognized not only in lung disease but also in liver disease as a result of increased focus on steatotic liver disease. There certainly is unmet need. Even though there are treatments, they're suboptimal. These are very exciting developments, and we look forward to the next steps. Thank you, Dr. Teckman. It's a pleasure to have you here with us today. As we disclosed in January, on the heels of significant regulatory engagement over the course of last year, we have reached alignment with U.S. FDA on a potential accelerated approval pathway for BEAM-302. To support the future BLA submission, we anticipate enrolling approximately 50 additional patients to be treated with BEAM-302 in an expansion of the ongoing phase I/II study. The primary endpoint is expected to be based on AAT biomarkers evaluated over 12 months. Continuing our track record for efficient and rapid execution. We're moving forward with multiple parallel efforts to maintain momentum in the ongoing phase I/II trial in preparation for initiating the pivotal cohort, which we expect to do in the second half of 2026. To start, now that we have selected 60 mg as our optimal biological dose, we plan to enroll additional patients in an expansion of Part A, as well as continue to enroll patients in the 60 mg cohort in Part B. This allows us to not only grow our safety database, but also to provide new sites in U.S. with BEAM-302 experience prior to initiating the pivotal cohort. At the same time, we're actively working to complete the pivotal protocol amendment, and recently we completed site activation at multiple U.S. sites. This builds on our already extensive global site network spanning 12 sites and six countries. At Beam, our commitment to leading innovation for the AATD community extends far beyond one program. In addition to our focus on advancing BEAM-302 to patients as efficiently as possible, we continue internal R&D efforts for future life cycle management. We're also deeply involved in the advocacy and research communities and serve as a member of C-Path's CPA-1 consortium in collaboration with the FDA to accelerate AATD research by identifying clinical efficacy endpoints, as a collaborator with Alpha-1 Foundation and Alpha-1 Europe Alliance to educate about gene editing and obtain a critical input on clinical trial design and patient experience. As we look ahead to the rest of the year, 2026 is shaping up to be a milestone-rich period for BEAM, with multiple value-driven catalysts on the horizon across our growing clinical portfolio. First, we remain focused on advancing our lead programs, including progressing BEAM-302 towards pivotal development in the second half of this year, following the data that we share today. Second, we expect to continue advancing the pipeline with key development milestones across several programs that leverage the same platform capabilities. Finally, we are doing this from a position of financial strength with a balance sheet that we believe supports the execution of our commercial, clinical, and development plans over the coming years. To close, at BEAM, everything we do is driven by our commitment to patients. The promise of base editing is not just about innovation. It's about transforming lives and enabling people to live the lives that we're meant to live. We are deeply committed to a vision of developing one-time life-changing therapies for patients. I'd like to thank the entire BEAM team for their tireless efforts and exceptional teamwork in advancing this program from inception to today. I'd also like to acknowledge that these findings today would not be possible were it not for the individuals whose lives we aim to change, people living with AATD. We'd like to thank all of our partners, including the investigators, the clinical site staff, our clinical development and manufacturing partners, the Alpha-1 Foundation, and other advocacy organizations around the world. Above all, each of the patients and caregivers who have taken part in our trials and made today possible. Operator, please open the line for Q&A. Thank you. Ladies and gentlemen, to ask a question at this time, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. As a reminder, in consideration of time, please limit yourself to one question only per person. One moment for our first question. Now, first question in queue coming from the line of Cory Kasimov with Evercore ISI. Line is now open. Hi, this is Eddy on for Cory. Thanks for taking our question. In the multi-dose cohort, how should we interpret the observed transaminase elevations? Are these events primarily a function of cumulative LNP exposure with repeat dosing? Are there any residual concerns around the safety profile that could impact the future dosing strategies as well? Thank you. Yeah. Thank you. Great question, and I'll pass that to Amy. Hi. Thanks for the question. I think with one event such as that, and the fact that it has very swift onset and a very rapid resolution along with some cytokine increases, we think it's likely driven by the inflammatory response to the second load of lipid. However, you know, given that I've mentioned it's just a limited number of patients, we're not entirely sure. But I think what's important is the LFTs resolved very quickly back to normal, and there was no evidence, for example, that the patient had symptoms, required any intervention. At the end of the day, I think that, you know, this is something that we think we didn't see with the single dose, which is very reassuring. We've now dosed, I want to remind people, 20 patients at the 60 mg and 75 mg doses with really just very consistent Grade 1 elevations in ALTs. I also just want to note that seeing Grade 1 elevations of LFTs or even Grade 2 are not really predictive of more severe events in the future, such as things like DILI. I think from that perspective, we feel very reassured, at this point in time with our single dose, and our optimal biologic dose chosen of 60 mg, x1. Thank you. Our next question coming from the line of Maury Raycroft with Jefferies. Your line is now open. Hi. Congrats on that great data, and thanks for taking my question. Wondering if you can talk more about just explanations for why the AAT levels at 60 mg are higher than your last update, increasing from 12.4 to 16.1. Is it due to higher baseline AAT, or dynamics with longer follow-up? Maybe a combination of both. Do you have a good understanding of the rate of AAT levels reaching steady state after dosing? Do you think that could continue to improve with longer follow-up? Sure. There's a lot in there. I mean, I think maybe just the first comment I'll make, and then I'll invite Amy to expand on it, is, you know, there's obviously a very significantly updated data set since last year. We went from n=3 to now, you know, n=6 with much longer follow-up, plus obviously expanding on the other dose areas as well. I think we commented last year, actually, we felt that the few patients we had at 60 were probably a little on the low end. I think you've seen that sort of normalize here. In terms of how the you know the overall data set has matured, I mean, I think that you know we see a lot of stability in the levels that we're achieving, and that you know is quite consistent with the mechanism of action of the drug. Yeah. I mean, I do think that over time, with more patients, we are seeing probably in the mean baselines that are more kind of what had been reported in the literature. Instead of having baselines of around five, we're kind of up in the range of about 6 μM at this time. I will say that once people, you know, hit day 28, they tend to kind of remain fairly stable from day 28. You can see all the way out now to as far as month 12. What we don't know yet is will the people who are at the lower doses, let's say the 15 or 30 mg, which are not close to kind of editing saturation, will they continue to increase over time because of the potential theoretic survival advantage that the cells that have corrected M-AAT would have over those that still have Z-AAT? Given the slow turnover in the liver of a, you know, t half-life of maybe 365 days, those drifts upwards over time in AAT levels may take a little time to see. In other words, one to two years may be kind of more along the lines what we would need to see. We're very pleased that we're seeing very strong, steady state levels and people maintaining those gains, you know, now in a durable manner. Thank you. Our next question coming from the line of Samantha Semenkow with Citi. Your line is now open. Hi, good morning. Thanks very much for taking the question, and congrats on all the great data and all the progress. I have a question for Dr. Teckman. Dr. Teckman, it would be great to just have your thoughts on what is most important here from an efficacy and safety standpoint in your view for a gene editing therapy specifically. When you look at the emerging profile for BEAM-302, how compelling is that mean 16.1 μM in total AAT? There's a few other additional gene editing therapies in the pipeline, and I'd love to get a sense on whether you think pushing that total AAT higher, if that's possible, would impact your view on the BEAM-302 profile as we see it thus far. Hi. Yes. Go ahead. Yes. Yeah, good question, and I think something that, you know, I've been thinking about and others have been thinking about. I mean, certainly there's some element of a continuum there, so, you know, more probably better. On the other hand, the curve of that line, it's not straight, right? I mean, it's actually a curve. As we've talked about, at the level that we're seeing, it's at least MZ, and that eliminates 95% of the risk. Plus it's better than that because in MZ people, half the, you know, protein they're making is Z. You know, in this situation, we see that really almost everything in the liver at that dose is converted. You have the acute phase reactant response preserved or restored. You know, do higher levels give some, you know, better protection? You know, possibly. This seems pretty good. I, you know, with regard to, you know, future treatments, hard to say. This looks pretty exciting. I mean, we've discussed this at the FDA going back a decade, you know, what should the target be? A lot of people have, you know, said, "Well, if you make people into carrier or better, then you've eliminated the vast majority of disease." Yeah, I think it's pretty exciting. Thank you. Our next question in queue coming from the line of Eric Schmidt with Cantor Fitzgerald. Your line is now open. Yeah, thank you. Some of the mean values you've produced here are really impressive, so congrats on that. I guess I'm wondering if there are any patient-specific factors that either lead to better or lesser gene editing efficiencies or whether maybe there's limited variability. As a follow-up, Peter mentioned that sites have already been activated in the Part C pivotal portion of this trial. I think some would probably claim that means the trial's already started, but what else are you guys waiting for to give us the green light on the go ahead there? Thanks. Sure. Maybe I'll take the first one and Giuseppe can clarify on the second one. I think the I don't think there's much to say yet on patient-specific factors. You know, generally, if anything, the results have been quite consistent across all types of patients and particularly now, you know, not missing the point that the Part B and Part A patients, that's probably the biggest factor we were already controlling for in the trial, where a Part B patient has, you know, known significant liver burden. As you've seen, the safety and efficacy of the 60 mg dose has been comparable there, which is very exciting. By and large, very consistent, frankly, across the full range of spectrum of patients in this disease. You know, in terms of the site network and then the path to getting the trial open. Yeah. By Amy's comments as well, but fundamentally it's, you know, we've made a protocol change, and we're in the process of the IRBs and the various sites to review that and to approve it. Obviously, we submitted that to the FDA as well. You know, they don't necessarily need to provide the input, but it's obviously always helpful to provide a little bit of time for them to comment, if they choose to do so. Fundamentally just the process of activating all the sites, making sure that the IRB reviewed it, we get approval. In the meantime, we are continuing, as I mentioned, some additional Part A treatment as well as Part B. I think that will provide basically almost like a training ground, if you will, for some of the U.S. sites, so they'll be ready for the pivotal trial. Amy, anything else that I may have missed? Yeah. Just to clarify, just so people know, the footprint that we're using is global, and that footprint is the exact same footprint we've used for the phase I/II study. When we talk about site activation for the pivotal, these sites have already been open for the phase I/II study, and now we'll just wind up conducting the pivotal with, as Pino mentioned, an amended protocol. The good news there is a lot of these sites have already had experience dosing people, kind of figuring out how to do this study, and this allows us to move super- fast because we don't have to then go to new sites that haven't been familiar with BEAM-302 or that then we have to wait for sites to come on board and contract, etc. I think we're gonna be able to move very fast using our existing global site network. Thank you. Our next question coming from the line of Brian Cheng with JP Morgan. Your line is now open. Hey, guys. Thanks for taking our questions this morning. Can you tell us a little bit more about how the additional 50 patients will be split across the lung and liver phenotype in the expansion portion? We know there's also a change in the way how you analyze total AAT here. Previously you used turbidimetry, and then here you use mass spec. Just curious if there's any potential influence in how we interpret the total AAT levels. Thank you. Go ahead, Amy. To answer your first question, I believe you wanted to know how the breakdown would be in the pivotal study for patients. In that study, what we're requiring is that everybody have evidence of emphysema. They don't necessarily have to have abnormal pulmonary function tests, but they have to have by at least CT scans and emphysema. They do not have to have liver disease, but they can have liver disease. What we're hoping here is we now have a pivotal cohort that is a spectrum of disease. Those with lung disease, with and without as well liver disease. It won't be divided into a Part A/B. It will be all together. We feel that our studies that we've done in Part A and B really assure us, to John's point, that the safety and efficacy should be the same whether or not you have liver disease. To get to the second point, we are using LC-MS because it is the preferred assay by the FDA to assess total AAT in circulation and enables us to test the AAT composition. With turbidimetry you can only just look at AAT, but with LC-MS we can look at this composition of M-AAT, Z-AAT. That's very important because it's not just the total AAT matters, but what is it made of. From that perspective, that's why we're switching to this. Now, in general, the values tend to be similar, but again, you would have to have, you know, each assay compared to each other. It's not enough to say like our LC-MS assay versus turbidimetry done at another hospital. We have our own validated assays, and we tend to do our assays side by side. Turbidimetry will have a role because it's a very quick turnaround time. We need that for things like eligibility and other things, but as far as endpoints go, it's gonna all be LC-MS based. Thank you. Our next question coming from the line of Yilan Xu with Wells Fargo Securities. Your line is now open. Great. Thanks for taking our questions, and congrats on the data. I have a question for the doctor and a very quick follow-up regarding an earlier question for the company. For the doctor, could you talk about what proportion for your AATD patients are candidates for this gene editing treatment and how many of them do you think would be interested in proceeding if you prescribe? For the company, the quick follow-up is on the Grade 4 liver enzyme question asked earlier. I was wondering, can you talk about the time course of this event, and how is it similar or different from the other Grade 4 liver enzyme elevations seen by gene editing, your gene editing peers? Thank you. Great. I'll start out. This is Jeff Teckman. Yeah, I think there would be a lot of interest from patients. I think that, like with a lot of new therapies, the use would expand over time. Most alpha-1 patients come to medical attention because of lung disease, at least in the past. There's a significant group of lung disease diagnosed patients and as we said, there is treatment with protein replacement, but it's suboptimal and a lot of lung physicians don't even use it. I talked to a patient last week who probably would benefit from it, but whose doctor told him not to be on it because he didn't like it or something. I think a new thing that's not gonna be weekly infusions and burdensome but is really gonna return people to an excellent defense of the lung. I think people would be very interested in that. I think there would be interest in people, especially as time goes on and it becomes more established, be interested in people from switching from infusions over, you know, to a one and done that really would be superior. At least, you know, that's our initial impression of the data. With regard to the liver, I think that it's extensive and more study would help us understand the impact. There are a lot of people who are gonna be diagnosed more frequently coming up. And again, if we have something to offer them, that is gonna be powerful and it's gonna drive diagnosis. I mean, speaking to the liver doctor, I mean, we test, just as an example, for Wilson's disease all the time, even though Wilson's is, you know, 10 x more rare than alpha-1 antitrypsin deficiency. It has a treatment, and if you can give it to people and save their life, you know, we send zillions of Wilson's treatments for the one out of 1,000 that comes back positive. In this case, there would be way more people with alpha-1 that we would identify and then bring the treatment to bear. I think it's the patients, especially over time, as we establish better data, are gonna be very interested. In answer to the second part of the question about the time course for the Grade 4 ALT elevation, this is very rapid. The ALT started to increase within two days. They probably peaked within five to seven days and were within normal limits even by the next visit at month four. This is a very rapid up down. As mentioned, the patients had no symptoms, was followed as an outpatient. There were no changes in bilirubin. Again, I think this time course is more consistent with what one might see and what had been seen before with LNP dosing. You asked about contrasting it a little bit to what was being seen, and I think you're referring to the Intellia data with some Grade 4 elevations. From what we can tell from what's out in the public domain, it seems like those are occurring later in time and being picked up about one month post-dosing or so. I think this is quite distinct from that. I will point out as well that as you can imagine, there's been no impact to efficacy either. You know, we don't think this is something that's like an antibody-mediated type of thing. We think this is more of a response by the body that you might see when you get a lipid load, like after a COVID vaccine, et cetera. More of an inflammatory response that's transient. Thank you. Our next question coming from the line of Mani Foroohar with Leerink Partners. Your line is now open. Hey, guys. Thanks for the question. A couple of quick ones. One, we've seen a lot of dynamism in response to inflammatory insults in at least one patient you presented today. How should we think about what that might imply in terms of functional outcomes, like clinical profile in a larger, longer pivotal study? I have a quick follow-up. Well, I think I mean just to clarify the question. I mean, clearly, we do think this is a dynamic mechanism. The gene is quite dynamic. It's one of the central parts of the acute phase response to inflammation. I think you actually said it well in the question. I think we think it's a fundamental part of the value proposition of the mechanism of action of this drug to, I think as we said, not only get you to, you know, a new floor, but have you be able to respond over time. You know, we will know when there is an induction event because we're also monitoring CRP, right? So, we're looking at inflammation in real time. You can tell the difference between, you know, a patient who's giving you the read on their new basal level over the long term, which gives you a sense of what their levels have been changed to after therapy, versus when someone's having an inflammatory event and the spike that happens as a result of that. Maybe just one point of clarification. The 16 μM steady-state level importantly does not include the 30 μM spike that has been seen. Just to give you a sense that that 16 μM is really very much basal, you know, a steady-state level measured over several months without incorporating the acute response. Thank you. Our next question is coming from the line of Michael Yee with UBS. Your line is now open. Great. Good morning, guys, and congrats. Matt on for Mike. I wanted to ask one for the doctor, maybe an add-on to a prior question. Could you just talk about how you use IV augmentation therapy now? What the weekly burden looks like for patients. I'm curious whether newer, longer-acting recombinant augmentation could change that. Then just overall, how does that compare to a one-time therapy like base editing from the patient perspective? Thanks so much. Sure. I'll just say I'm a liver doctor. I'm very familiar with the lung disease, so I don't personally prescribe protein replacement for alpha-1, but I'm very familiar with it. Until recently, it's all purified from human plasma and, yeah, people have to have IV started or they have to get a port and it's disruptive to travel and, you know, things that people wanna do. I again wouldn't underestimate what the problems with the therapy are. Like I said, it helps people, but it doesn't return people to wild type and such that many people in the pulmonary field don't use it because they don't feel that the risk-benefit and cost ratio is even worth it. I don't agree with that, but that is a strong opinion among lung doctors, some lung doctors. With regard to the recombinant or long-acting, you know, that might actually be a bad thing because as we've said, when you're sick you need more alpha-1. It gets used up. We didn't really talk about this, the actual physiology. When alpha-1 antitrypsin protein does its job, which is to inactivate neutrophil proteases. When neutrophils are moving through tissue, as part of their attack against bacteria, they use proteases to open some pathways in the tissue. Alpha-1 is present in this fluid between cells and in serum to inactivate that, so that that effect doesn't spread, as well as when neutrophils phagocytose and there's some leakage of proteases. Again, alpha-1 is there so that it protects. When you have an active infection, you use up the alpha-1 antitrypsin protein. Its mechanism is it binds, it's a suicide binding to a molecule of neutrophil elastase, for example, or other neutrophil proteases. You use it up. If you have the long-acting, I mean, it's great that it has a long half-life in circulation, but if you're getting infusions once a month instead of once a week and then you get an infection, your next infusion is for three weeks, you're suddenly unprotected 'cause you used up all the alpha-1 that you've got. The acute phase response and restoring that theoretically would be a major advance in lung protection. Again, we have to see the data, but I mean, people have thought about this and hoped that there was something that would restore the acute phase response in this disease for a long, long time. There are even people who are on protein replacement who in the past especially would hoard it and then try to infuse more when they were sick because they felt like they when they got sick that they had a you know step down in their lung function. I think this is important, and I don't think the long-acting replacement is gonna nearly match, at least if these results are borne out the infusion is not gonna be as good. Thank you. Our next question coming from the line of Luca Issi with RBC. Your line is now open. Well, great. Thanks so much for taking my question. Congrats on the progress here. Maybe, John, kind of high level, any quick thoughts on the competitive landscape here? I'm wondering what was your reaction to GSK returning the rights to Wave. Maybe on the other side also your thoughts on Yoltech, which I believe in China showed more than 20 μM of total protein at, I believe, at just 40 mg-45 mg. Again, any thoughts there are much appreciated. Maybe super quickly, Giuseppe, on the regulatory side, again, appreciate your staff here for accelerated approval on AAT biomarkers. What's the bar here that the FDA is looking for? Do you need to show all patients above 11 μM? Do you need to show a specific ratio between M and Z? Like, any additional color on what the FDA is looking for here, much appreciated. Thanks so much. Great. Yeah. Thanks for the question. I'll take the competitive one, as you noted. You know, we think we're in a very strong position. This is gonna be a huge indication. We have a very clear first mover advantage. You know, we're now up to almost 30 patients and moving directly into a pivotal trial now with alignment on the FDA for the path to market. That puts us, you know, several years ahead of everyone else. There obviously will be more players. You know, as you noted, I think the RNA editing field. I think, you know, we await more data and see if those agents can produce the kind of profile we're seeing here. I think, you know, we clearly believe that this will be a best in class relative to that. You know, look forward to seeing more. For future DNA editing agents, obviously, I mean, Yoltech there, the couple of patients reported in China, we have to wait for more there. You know, only one of which was at the level you described. Other DNA agents moving into the clinic over the course of this year, we'd probably get some data, you know, in a year or so. You know, I think we have a very strong lead over them. I think the most important thing is the fact that, you know, as Dr. Teckman was commenting on the risk levels, you know, we think we've done what we needed to do to get rid of the risk of disease. It doesn't clearly, to me, leave any room for a lot of improvement that would be detectable in any kind of reasonable clinical experiment you can do. I mean, that's the whole point of getting to carrier here is, you know, unless someone's a smoker or something like that, you know, you're not gonna see any progression in the disease, whether you're where we are now or anywhere else that people can try to get to. Bottom line, I think it puts us in a very strong position. The other thing competitors talk a lot about, you know, as you know, is bystander editing and invariant. You know, I think we are very confident, as we've shown before in our preclinical data, that the variant acts completely normally relative to the normal protein. I think we have a lot more data now in the clinic building up that we do share over time. That I think will also, you know, not be a source of competitive advantage over time. In terms of the pivotal cohort, maybe I'll pass that on to Pino to address. Yeah. Look, in terms of what is approvable, there is no real, sort of, you know, sort of hurdle specifically in terms of the level or MZ ratios that the FDA requires. Certainly not expressed to us. I think with the way we handle the conversation with the FDA, we shared the data that we shared with you in the last year, and basically we asked the question, "If you saw this in the pivotal trial, will this be approvable?" The answer is yes. The data that you see today is very consistent with that, and we do believe that that is approvable. Obviously, in the pivotal trial, we will need to see consistent, you know, sort of responses to this data. If we do so, we do believe that that is approvable. Thank you. Again, please limit yourself to only one question. Our next question coming from the line of Alec Stranahan with Bank of America. Your line is now open. Hey, guys, this is Matthew on for Alec. Congrats on the data, and thanks for taking our questions. First one from us, I guess, just curious, you know, the percentage of bystander or passenger edits, is it similar to the previous update, the 60 mg? And sort of how did those pan out at 75 mg in the multi-dose cohort? And then maybe a quick one, double-clicking. Curious whether you're seeing those with higher AAT at baseline have more pronounced increases in, you know, total AAT or the M proportion. Just trying to dig in there a bit. Yeah, maybe I'll handle that. I think, again, nothing different clinically than we've seen pre-clinically in terms of the editing profile and the outcomes. That's true at 60, 75, and multi-dose 60. Again, those are all, you know, quite comparable. Just to your, I guess, your question about baselines and just sort of patients, you know, at a higher or lower baseline. You know, we do think that that's probably physiology, right? That a patient who lives at the high end of maybe their baseline is gonna be a higher outcome after editing versus low end. You know, it's very small n, so we'll obviously be learning more over time about those nuances. Thank you. Next question in queue coming from the line of Whitney Gim with Canaccord Genuity. Your line is now open. Hi, guys. This is Angela on for Whitney Gim. We'll add our congrats and thank you for taking our question. Just curious, has there been any discussion with regulators in terms of wanting to see an acute phase response in the pivotal? Will there be any endpoints related to that? I guess at this point, are there any more conversations that need to be had with the FDA, or do they have all the feedback in terms of getting the pivotal started? Thank you. Yeah, I'll take that. The answer to your second question is no, we don't need to have any further interactions. I think we have the clarity on what it takes to do the pivotal trial and what would be acceptable. There was no specific conversations around needing to see an acute response in pivotal. However, you know, we'll keep on monitoring, and we do believe that on average, we're expecting to see that, just by virtue of the fact that people are exposed to very severe infections and so on. We think it will be part of that data set, but it's not a specific requirement. Thank you. Our next question coming from the line of Myles Minter with William Blair. Your line is now open. Hey. Congrats on the data. My question's actually for Dr. Teckman. I was just wondering whether you're aware of the SPARTA trial that's going to read out at the end of the year for double dose of AAT augmentation therapy. I know it's measuring lung function and RV, DLCO, so I understand that. But if that did show functional superiority with a higher dose, does that move the 11 μM sort of bar that we're looking for efficacy associated with serum AAT levels that's the target here? Just curious of your thoughts there. Thanks. Right. You're referring to the double dose trial, which has been going on for a while. Yeah, this is the dose of augmentation, protein augmentation therapy was arrived at almost 40 years ago, and the reasoning behind that has sort of been reworked. The thought, part of the thought behind why augmentation doesn't return people to wild type is that the dose was too low. Also when you talk about the dose, and the levels reached, you know, people are obviously you give it and it goes down over time till the next infusion, right? It was natural to m- Somebody finally did a higher dose. It's hard to get payers at this point to pay for higher dose or double dose. I think there has been some preliminary evidence that released from those trials which, you know, might probably better, but it doesn't return the acute phase reactant thing. I think there's more to do there. There's still the infusion burden. The infusion would be longer, it would be more expensive. The other thing we really didn't touch on so much is that there is this data and idea that the Z protein polymers are actually damaging to the lung. In the liver it's definitely a storage disease. There is evidence that there's polymer deposition in the periphery, in blood vessels and in the lung. There's evidence that the, these little polymers are chemotactic for neutrophils. Alpha-1 emphysema is known to be more neutrophilic than the usual emphysema. There's some evidence that this actually is a thing. Getting rid of the circulating Z 95%, as was shown here, that might also help the lung as well. Of course, protein replacement doesn't do that. I think protein replacement has helped some people over the last 40 years, but I think it's ready to be replaced by better things. I don't think it's gonna continue on with some of these new treatments which are gonna be so much better. Thank you. Our last questioner will come from the line of Patrick Trucchio with H.C. Wainwright. Your line is now open. Hi, this is Arabella in for Patrick. Thank you so much for taking the question and congrats on the data. I guess I was wondering if you could comment on what drove the numerically lower AAT, the 14.4 μM versus 16.1 μM at the 75 μM versus 60 mg cohort. What drove a lower number instead of just a plateau. Then on the side of near saturation editing at 60 mg, do you have any direct measurement of editing efficiency in the liver or is this inferred from circulating protein biomarkers? Thank you so much. Thanks. I'll close this out here. I think on the latter it's all inferred. We don't have editing rates yet. We'll pick that up over time with biopsies. But I wouldn't read too much into the 14.4 μM versus 16.1 μM. I think that, you know, if you look at the aggregate AAT levels across the 60 μM, 75 μM and the multi just 60 μM, you know, you look at the percent Ms were all in that sort of, you know, low 90s, 90, 95. You look at the Z reduction. You know, we think that those are more comparable than not, and they certainly overlap statistically significantly. You know, I don't think we're picking up any real signal there. Most likely, obviously, with more follow-up, we'll learn more over time. Thank you. I will now turn the call back over to Mr. John Evans for closing comments. Thank you very much. I want to thank you all for your time. It's an exciting day. We're so pleased to see this continue to mature and really looking forward to partnering with the community to getting this to patients as quickly as we can. I want to thank Dr. Teckman for joining us and for the great insightful commentary and help along the way, and we look forward to sharing more of this with you as this moves forward. Thank you very much. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.