All right. I show we're at start time. I'll be transferring now. Good luck, everyone. Good day, and thank you for standing by. Welcome to the Agios Pharmaceuticals European Hematology Association 2026 Investor Webcast and Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, we'll open up for questions. Please be advised that today's call is being recorded. I would now like to hand it over to our first speaker, Morgan Sanford, Head of Investor Relations at Agios. Please go ahead. Thank you, Operator. Good morning and good afternoon, everyone, and thank you for joining us. We're pleased to host today's webcast in conjunction with the 2026 EHA Congress, where we are presenting a broad set of data across our portfolio. You can access the slides for today's presentation on the investor section of our website. Please note that we will be making forward-looking statements during this presentation. Actual results may differ materially due to risks and uncertainties described in our SEC filings. Joining me today are Brian Goff, Chief Executive Officer, Dr. Sarah Gheuens, Chief Medical Officer and Head of R&D, and Tsveta Milanova, Chief Commercial Officer. We will also be joined for Q&A by our participating key opinion leaders, Dr. Alan Anderson, Associate Professor of Pediatrics at the University of South Carolina School of Medicine Greenville, and Director of the Comprehensive Lifespan Sickle Cell Disease Program at Prisma Health, and Dr. Kenneth Ataga, Plough Foundation Endowed Chair in Sickle Cell Disease and Director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center. With that, I'll turn the call over to Brian. Thanks, Morgan, and good morning and good afternoon to everyone. We appreciate you being here and are excited to share new data presented this weekend at the 2026 EHA Congress here in Stockholm, strengthening the profile of mitapivat across thalassemia and sickle cell disease. I'd like to start by highlighting the evolution and strength of our rare disease business at Agios and why this is a pivotal moment for the company. We're transitioning from a single asset story to a multi-asset, multi-indication platform with multiple independent drivers of value now coming into focus. At the same time, our execution and clinical data are meaningfully de-risking the PK activation platform in hemolytic anemias, which include two PK activators, mitapivat and our next-generation asset, tebapivat. We've demonstrated that we can translate biology into clinical benefit. Importantly, we're building strength and momentum in our commercial capabilities to launch and grow these medicines in a repeatable way. Looking ahead, we have multiple near and midterm catalysts over the next 12- 24 months. From our continued scaling of the U.S. commercial launch of AQVESME and thalassemia to potential advancement into larger rare hematology populations, including sickle cell disease, polycythemia vera, also known as PV, and immune thrombocytopenia, referred to as ITP. Taken together, this is not just about any one program. It's about a broad and increasingly diversified pipeline targeting multiple large, underserved, rare hematology communities. Guided by these principles, we are executing a strategy that extends our leadership in hemolytic anemias with selective expansion into adjacent rare hematology opportunities where we see clear pathways to innovate and lead. This slide captures where and how we are driving targeted disruption across rare diseases. We are highly selective, focusing on underserved rare disease communities where the biology is well understood, the disease burden is significant, and current treatment options remain limited. In thalassemia and sickle cell disease, we are building from a foundation of PK activation where we've demonstrated the ability to translate mechanism into durable, clinically meaningful outcomes. At the same time, we are intentionally diversifying our portfolio with assets supported by unique mechanisms and best-in-class potential, including next-generation SYK inhibition in ITP and siRNA TMPRSS6 inhibition targeting polycythemia vera. These are areas where we believe we can deliver differentiated profiles with the potential for improved tolerability and durability of treatment effect. Beyond hematology, we're applying the same mechanism-driven approach in phenylketonuria, or PKU, where we see the potential to bring a disruptive new therapeutic option to patients. Across each of these opportunities, the strategy is consistent. Focus on biology, execute with discipline, and target areas where we have potential to transform the standard of care. This is not broad diversification. It is selective, grounded in science, and designed to create value across multiple independent clinical programs. Within that framework, AG-236 represents a clear expansion into an adjacent rare hematology disease, PV. Following completion of the phase I healthy volunteer study, we've made the decision to advance the program into late-stage development for this indication. The data demonstrate clear dose-dependent hepcidin induction along with strong and sustained pharmacodynamic activity and a favorable tolerability profile. Importantly, these results in healthy volunteers support the potential for up to every six-month dosing with consistent exposure in patients, a meaningful advantage in a chronic disease setting. In an evolving landscape, we believe AG-236 is well-positioned to advance chronic treatment for PV patients with a profile defined by extended dosing without titration, strong tolerability, and durable activity. These are important elements to redefine the treatment of PV. We look forward to discussing our development plans following end of phase I interactions with the FDA. Given the evolving treatment landscape, we are prioritizing speed and disciplined execution as we approach late-stage development for this clinical program. With that, I'm pleased to turn the call to Sarah to review our data presented at the 2026 EHA Congress this weekend. Sarah? At this year's EHA Congress, Agios is presenting a broad and comprehensive data set for mitapivat across multiple hemolytic anemias, including 10 accepted abstracts and an oral plenary presentation of the RISE UP phase III trial in sickle cell disease. Across these presentations and publications, our goal is clear: to demonstrate consistent, durable, and clinically meaningful impact across multiple rare diseases. Starting with thalassemia, we shared long-term data from the open-label extension period of the ENERGIZE phase III trial in adult patients with non-transfusion-dependent alpha or beta thalassemia. These data show sustained and clinically meaningful hemoglobin improvements over time. In patients that continued on mitapivat into the open-label extension period from the double-blind period, the mean duration of hemoglobin response more than doubled from 17.9 weeks to data cutoff at 43.6 weeks, with responses still ongoing at the time of data cutoff. Notably, patients who switched from placebo to mitapivat in the open-label extension period achieved hemoglobin improvements consistent with those seen during the double-blind period, reinforcing reproducibility of effect. Additionally, data from the open-label extension trial showed a robust proportion of hemoglobin responders. Nearly 60% of patients that continued on mitapivat into the open-label extension period demonstrated hemoglobin response, defined as at least 1 g per deciliter improvement from baseline in average hemoglobin over any two consecutive visits in the open-label extension period. This represents an increase from the 42.3% response rate observed during the double-blind period of the trial, suggesting that response rates may improve with longer exposure. Additionally, approximately one-third of prior non-responders in the double-blind period achieved hemoglobin response in the open-label extension period. Furthermore, we observed a nearly 50% response rate amongst placebo patients switching to mitapivat in the open-label extension period. Across the open-label extension data, the mean change from baseline in hemoglobin was 1.3 g per deciliter. Importantly, there were no new safety events that changed our understanding of the safety profile of mitapivat in thalassemia. Another interesting data set presented this weekend is a post-hoc subgroup analysis also from the ENERGIZE phase III trial. It focuses on patients with higher baseline hemoglobin levels, defined as at least 9.5 g per deciliter at baseline. A group where treatment effect is typically more challenging to demonstrate. Despite this, mitapivat shows clear biologic and clinical activity. 38.9% of patients achieved a 1 g per deciliter or more hemoglobin increase. This was accompanied by a clinically meaningful improvement in fatigue, with a 5.1 point change in FACIT fatigue scores based on least squares mean change from baseline from week 12 to week 24. These data support a consistent treatment effect across baseline hemoglobin levels and reinforce the potential for mitapivat to provide benefit across a broader non-transfusion-dependent thalassemia population. I'll also briefly highlight data from the SATISFY phase II trial. This is a collaborator-led study that helps contextualize the biologic effects of mitapivat across rare hemolytic anemias, including hereditary spherocytosis, hereditary elliptocytosis, and Congenital Dyserythropoietic Anemia Type II. At 56 weeks, we saw sustained activity across multiple domains. Hemoglobin improvements are maintained over time, with nearly half of patients achieving response, defined as an improvement of at least 1 g per deciliter during the fixed-dose period two. We saw rapid and sustained reductions in hemolysis markers, including reticulocytes and bilirubin, and importantly, these upstream effects translate into reductions in iron burden, an important marker of downstream complications in hemolytic anemias. Together, these data reinforce a direct effect on the underlying pathophysiology of hemolysis, with evidence that improvements extend to downstream disease consequences. This consistent biologic profile provides important context as we now turn to the RISE UP phase III data set of mitapivat in sickle cell disease, where these effects are evaluated in a large randomized setting. The RISE UP phase III trial is a global randomized placebo-controlled study evaluating mitapivat in patients aged 16 years or older with sickle cell disease. The study enrolled 207 patients above targets of 198 patients and randomized them 2: 1 to mitapivat or placebo over a 52-week double-blind period. The dual primary endpoints were hemoglobin response and the analyzed rate of reduction in sickle cell pain crisis. Key secondary endpoints included measures of hemolysis and fatigue. Here we see the primary efficacy results from RISE UP, reinforcing mitapivat's role as a strong anti-hemolytic agent. Mitapivat demonstrated a 40.6% hemoglobin response versus 2.9% on placebo, with responses maintained through week 62. Among responders, the mean increase in hemoglobin was 1.6 g per deciliter, reflecting a clinically meaningful improvement. We saw rapid and durable improvements in both hemoglobin and indirect bilirubin, with clear separation from placebo and sustained effects over time. This consistency across multiple endpoints reinforces mitapivat's anti-hemolytic mechanism of action, with aligned improvements across key biologic markers. While we did not achieve statistical significance on the trial's other primary endpoint, the annualized rate of sickle cell pain crisis, or the key secondary endpoint of change from baseline in PROMIS fatigue, we observed directional responses favoring mitapivat over placebo across key measures of hemolysis and other sickle cell pain crisis-related endpoints. Importantly, hemoglobin response translated into clinically meaningful benefits across key disease outcomes in sickle cell disease. Compared to non-responders, hemoglobin responders experienced reductions in sickle cell-related events, including a 26% reduction in annualized rate of pain crisis, 34% fewer hospitalizations, 53% reduction in the annualized rate of ER visits for sickle cell pain crisis, and a 37% reduction in the annualized rate of hospitalization days for sickle cell pain crisis. In addition, we see a clinically meaningful improvement in fatigue based on the PROMIS fatigue measurement scale. These data reinforce that for patients who demonstrate a hemoglobin response on mitapivat, there is potential for downstream clinical benefit, including sickle cell pain crisis measures and fatigue. In a new post-hoc analysis presented for the first time here at the 2026 EHA Congress, hemoglobin responders showed improvements across a number of other patient-reported outcomes. All of these measures, including pain, sleep, and physical function, favor hemoglobin responders compared to non-responders. The safety profile for mitapivat was favorable overall, with adverse events broadly balanced between the mitapivat and placebo arms, lower rates of serious and Grade 3 or higher adverse events versus placebo, and no treatment-related deaths. Importantly, we also see a clinically meaningful reduction in transfusion requirements. Mitapivat reduced the proportion of patients requiring transfusions by 41% and the number of units transfused by 66%, relative to placebo in the total patient population investigated in the RISE UP phase III trial. These are highly relevant endpoints in sickle cell disease, reflecting real-world disease burden. When benchmarked against historical data with hydroxyurea, which shows approximately 30% reduction in transfused patients and 37% reduction in units transfused, the magnitude of effect observed with mitapivat is notably greater across both measures. Importantly, these data informed the design of the REIGNITE phase III confirmatory trial under the U.S. Accelerated Approval Pathway, which has a primary endpoint defined as transfusion-free from week four through week 62. On the next slide, you can see the design of the REIGNITE phase III trial intended to confirm clinical benefits of mitapivat in sickle cell disease. The REIGNITE trial is a 62-week global, double-blind, randomized study evaluating transfusion independence along with additional measures of transfusion burden, hemoglobin response, and hemolysis. We are also enrolling patients aged 12 and older, supporting the potential to expand the label beyond the 16 and up population studied in RISE UP. The REIGNITE trial was informed by the transfusion benefit data generated from the RISE UP phase III trial, including powering for the primary endpoint as well as effect size. Additionally, we leveraged insights from the RISE UP trial to inform other assumptions for the confirmatory trial, including dropout rates and baseline characteristics. We intend to enrich for patients with clinically meaningful disease burden requiring at least one packed red blood cell transfusion in the prior 12 months, baseline hemoglobin of 5.5- 10.5 g per deciliter, and additional evidence of hemolysis to support a measurable treatment effect. What's most important in the RISE UP data set is the consistency we're seeing between biology and clinical outcomes. Mitapivat delivers a reproducible anti-hemolytic effect across the overall patient population, which aligns with its mechanism. And in patients who achieve hemoglobin responses, those improvements translate into meaningful clinical benefits, including on sickle cell pain crisis measures, fatigue, and other patient-reported outcomes. Importantly, the RISE UP analysis now show that this effect also drives a clinically meaningful reduction in transfusion burden, which we view as a key indicator of impact on disease severity for sickle cell patients. All of this is supported by a large and maturing safety database, now exceeding 1,300 patient-years across three hemolytic anemias, an important consideration in a chronic disease like sickle cell disease. Taken together, we strongly believe mitapivat represents a differentiated anti-hemolytic approach with the potential for a meaningful clinical impact in this underserved patient population in desperate need for innovative therapies. What this slide highlights is the repeatability of the PK activation mechanism across multiple hemolytic diseases. In PK deficiency, we've already established that activating PK can drive meaningful and durable improvements in hemoglobin and transfusion burden, with long-term safety now well-characterized in both adult and pediatric populations. We then see that that same biology translates into thalassemia, where mitapivat delivers consistent improvements across both transfusion-dependent and non-transfusion-dependent populations, including patient-reported outcomes, which is an important proof point. And in sickle cell disease, we're again seeing a consistent anti-hemolytic signal, with hemoglobin improvements translating into clinically meaningful outcomes in responders, supported by a favorable safety profile. Therefore, across three distinct rare diseases, the data consistently shows that targeting red blood cell metabolism can drive both biologic and clinical benefits. We view our PK activation portfolio, which also includes tebapivat, our next-generation PK activator being explored in sickle cell disease, as a validated and scalable franchise, not a single asset story. Now, I'm pleased to introduce Ahmar Zaidi, our Senior Medical Director for Sickle Cell Disease and an accomplished pediatric hematologist in his own right, who will moderate the fireside chat with Dr. Kenneth Ataga and Dr. Alan Anderson. Hello, everyone. I'm Dr. Ahmar Zaidi, Senior Medical Director in Clinical Development at Agios Pharmaceuticals, where I lead the development of mitapivat in sickle cell disease. Before joining Agios, I spent nearly a decade caring for people living with this catastrophic illness, that clinical experience continues to shape how I think about the field. Today, I'm pleased to be joined by Dr. Kenneth Ataga and Dr. Alan Anderson, two leaders in the sickle cell disease care and research fields. Together, we're going to discuss the current burden of sickle cell disease, mitapivat, the RISE UP clinical program, and the future of pyruvate kinase activation. Dr. Ataga and Dr. Anderson, welcome. I want to dive right in and talk a little bit about the state of sickle cell disease as it exists today. You both collectively spent decades caring for patients with this illness. How would you characterize the burden of this particular disease in patients today? I'm lucky to have the perspective of seeing patients across the age continuum, what I recognize coming from a pediatric background is that we were seemingly doing good work with one disease modifier, with hydroxyurea, patients were seeing the improvements in terms of reduction in stroke and pain events, decrease in acute chest syndrome, some of those things. What I now recognize wearing an adult hat is that the adults were still significantly struggling, not only struggling to find locations for treatment, also struggling to limit the organ-damaging effects of the disease over the lifespan, that single modification therapy is just not enough. I think the major deficit that I see across the spectrum is that our adults are still living 30 years less, in terms of their life expectancy than age-matched counterparts without sickle cell disease. They lack options for disease modification, they have this cumulative toxicity of the disease that we see coming over time without great options so far for us to be able to impact that and prevent it. Does that resonate with you, Dr. Ataga? Yeah, definitely. The one thing I would add to what Alan has said is the fact that sickle cell disease is very heterogeneous, right? Within patients and between patients, they can have varying severities of disease at certain times and different times. We also know that as patients get older, they have this cumulative progressive organ damage. I remember a few years ago, there was some controversy, locally, because someone had said something to the effect that, "Oh, we take good care of children, and then they come to the adult side and die." Which was misinterpreted to mean that adult providers did not do a very good job, right? I don't think that's what that provider meant by that statement. It just kind of illustrates the fact that as patients get older, they have this cumulative and progressive organ dysfunction, which increases the risk of dying. It just tells us that we need to do more work in order to try and improve the care that provide patients with sickle cell disease, prevent complications from developing, help them to lead better quality lives, and survive for much longer as well. That's really important clinical framing. Thank you for those perspectives. I'd like to dive a little bit into the pathophysiology around the disease and get a sense from the both of you around the importance of addressing chronic anemia and hemolysis in the overall management of sickle cell disease as you think about patients holistically. Let's go ahead and start with you, Dr. Anderson. I think what I talk to my patients about every visit is that the crux of the issue in sickle cell disease is the fact that that red cell changes shape, dies too quickly, and ultimately the downstream effects of that are release of all these inflammatory cytokines. We know that that chronic inflammation is leading to damage within the organs, and it's a continuum. It's a latency period until which that individual is going to develop significant enough damage in that organ to cause organ failure. Everybody's moving along that pathway in some degree. What I wanted to really draw my patient towards is that that damaged red cell that's dying too quickly is leading to all the downstream complications, and that is that that fast turnover of the cells is leading to the chronic anemia. What we're trying to do now is have our patients recognize that anemia is at the crux of the issues that they have with fatigue, with inability to tolerate activities that they want to, whether that's sporting activities, school performance, whether that's work-related things, and trying to use the right questions to ask a patient about what it is they want to see improved. I think historically, our patients, what I've noticed is that they will not know how to necessarily say that, "I want to see this improved." They're so used to having the fatigue, having this inability to do the things that they want to do. Asking the right questions to really tease out what is it you want to see improved, and how can we showcase that this is related to the chronic hemolysis and anemia that you've experienced. I think it's when we connect those things that you really start to see patients desiring to see improvement in their hemoglobin, to see a reduction in hemolysis and the downstream effects. Thanks for that, Dr. Anderson. Dr. Ataga, this is something you've published about. I'd love to hear your perspective. I think it's important to understand that much of the problems we see in patients with sickle cell disease are driven by vaso-occlusion, as well as hemolysis. It's not just one. There's significant overlap in terms of how, what leads to problems in patients with sickle cell disease. It's not that one problem is caused purely by hemolysis and one is caused purely by vaso-occlusion, but this exactly interacts. Lots of studies also show significant relationships between hemolysis, hemolytic anemia, and a variety of complications in patients with sickle cell disease. We know that anemia is bad, and it doesn't matter whether you have sickle cell disease or not, right? It's particularly bad in patients who have sickle cell disease. Like Alan said earlier, there's lots of studies that show associations between anemia and lots of problems. Increased mortality in these patients and organ dysfunction. Increased risk of stroke, for example, abnormal TCD velocities, patients who might have pulmonary hypertension, kidney disease, and so on and so forth. It drives lots of things, fatigue and all of that. I think what we haven't really shown in a prospective manner is the fact that if we're able to fix this problem, then we can actually mitigate or prevent this problem from developing, right? Intuitively, it would seem like that, but we need to kind of prove that. I think we are getting there now with the new therapies that we have coming on board, that if we're able to do that, we could actually prevent many of these problems. I think where we have shown that somewhat is the case of patients who have abnormal TCD velocities. Alan treats patients who treat children who are at high risk for stroke. I'm an adult hematologist, so I don't really treat. I don't get TCD velocities myself. In those patients, we know that transfusion therapy does help to decrease the risk of abnormal TCDs, and there's also data for use of hydroxyurea as well, which might work at least in part from increasing hemoglobin levels in these patients as well. I think now that we're having therapies come on board that seem to have more robust effects on hemolytic anemia, we might see even greater benefits in decreasing or perhaps preventing some of these complications. We need to do these studies going forward and see if what we think happens, if it's actually correct. I'd love to shift the lens of this conversation just a little bit towards clinical trials. The FDA has recently discussed the inherent challenges that sometimes are associated with the vaso-occlusive crisis endpoint. When you think about vaso-occlusive crisis as a clinical trial endpoint, how do you sort of think about that when compared to other measures of clinical benefit? I'd love to start with you, Dr. Ataga, on this question. All right. That's a good question, and that's a discussion we have a lot as sickle cell doctors, right? I think for one, most of the big studies in sickle cell disease have focused on vaso-occlusion as painful crisis as the primary endpoint. That's not particularly surprising because this is the most common reason for which we see patients. That's what most of the studies have focused on this endpoint. Many of the studies have not been successful trying to address this endpoint as well. Many people have speculated or suggested that maybe we should stop looking at painful crisis as an endpoint because many of these studies have not been positive. I don't think we can ignore it. I think what we need to do is we need to try and see if we can better define this problem in patients with sickle cell disease. It's a very difficult problem to define because it's subjective in terms of pain. We don't have any biomarkers that can tell us that someone is having pain or not. It's not like there's some test you can do that tells you a patient is having pain or the pain has resolved. I think there's a variety of ways the definition can be improved because it's problematic. When we look at the current definition of painful crisis, it's confounded by a variety of factors. For one, if I'm thinking of patients getting opioid analgesics, the patterns of use of opioid analgesics differ depending on where you live in the world. If you live in Memphis, Tennessee, where I live, compared to a patient who lives in Mali or in Côte d'Ivoire or in Nigeria or in Ghana, or even in Europe, in the U.K., for example. I agree 100% with what Ken was talking about, and just in terms of there being inherent differences in how we manage pain here in the United States, let's say, versus on the continent of Africa, where I have seen in working in multiple places that it is much less common to have access to high-potency narcotic pain medications. Versus here in the United States, where for a long time it was validated to say we needed to check a pain scale on everyone every time they touched the health system, and we sort of conditioned individuals to have as close to zero pain as possible. We have worked long and hard to find the right balance in sickle cell disease in blocking pain when we can, but also understanding that pain can be driven by things outside of just sickling. The mental health of patients goes into that. All of these things can be center-specific, geographic-specific, et cetera, and can ultimately have an impact on the VOC incidence that is seen in that specific trial. These are wonderful clinical perspectives. Thank you so much for offering them. I'd love to move our conversation forward to talk a little bit about the RISE UP clinical program and mitapivat specifically. Why don't we start by just talking about our primary takeaways from the RISE UP phase III results? I'd love to hear from both of you. Dr. Ataga, why don't we start with you first? I think this was a very important study that showed, for one, in a large group of patients across the world, pretty much, global study, looked at patients in the U.S., in Europe, in sub-Saharan Africa, that treatment with mitapivat, which is this pyruvate kinase activator, increases the likelihood of patients having what's called a hemoglobin response. In a large number of patients, roughly about 40% of patients had this hemoglobin response, in which the hemoglobin went up by at least 1 g, when you compared them from baseline after between 24 and 52 weeks, compared to patients who got a placebo. The study did not show any significant differences between patients who got the active medicine and placebo in regards to annual rate of pain episodes. In those patients who had a hemoglobin response, there did seem to be a meaningful decrease in the frequency of pain in these patients. I would say that I was extremely excited to see just how robust the hemoglobin response was and how the hemoglobin response in the RISE UP trial also correlated with reduction in hemolysis. LDH, percent reticulocyte count, measures that we know go along with, also bilirubin, they go along with the hemolysis that our patients are experiencing. Not only was the hemoglobin response very robust, but also happening very quickly. Our patients want to see that. They want to see that if they start something, that they're seeing the benefit of that and, in the trial results, seeing that happening in the first two weeks of treatment with that first CBC time point. The other thing that we want to see in a trial like this is the durability of the hemoglobin response. Seeing that hemoglobin rise greater than 1 g per deciliter, and then maintaining over that, in the trial results, showing between week 24 and week 50, durability of that hemoglobin response. All those things are very exciting. I think as well, the tolerability that was seen in the results. Side effect profile was very mild and mostly self-limited in terms of the side effects that we're seeing. I think also just seeing that there is historical data on the use of mitapivat in PK deficiency, in thalassemia, and then that same efficacy and safety profile has been seen before. That's going to be important to our patients because they've sort of been burned with results in the past where they felt that things were safe or certain results of the trials, and then to find out later that there were concerns. I think that patients are wanting to see that the results have held up over time, and in this case, in different disease populations. I think that we're going to see that's beneficial. The transfusion, decrease in transfusion burden, I think is extremely important, especially as we look at some of our adult patients that have developed iron overload and alloimmunization and other things where we need to try to reduce the need for transfusions. We'll see about pain over time. I'm also reassured by the responder analysis that showed a meaningful decrease in pain in those who were responding. My hope is that we'll see that play out with this type of a therapy in the future as well. Just to follow on to that, when you think of the RISE UP data, Dr. Ataga, what patients do you believe are most likely to benefit from mitapivat? How are you thinking about where mitapivat sort of places itself in the clinical context? That's a good question. From the RISE UP study, everyone seems to benefit, right? When you look at the subgroups, whether that was based on age, whether that was based on genotype, based on hemoglobin levels, patients seem to benefit. All patients seem to have adequate benefits to the intervention. Having said that, there were eligibility criteria set back in the study, patients had to have hemoglobin levels of between 5.5 and 10.5, right? The question is, if you have someone who has a hemoglobin of 11 or 12, is that someone you should consider putting on a drug like mitapivat? It's not very clear, right? We don't have data to support that. We as sickle cell doctors always get worried when the hemoglobin level goes too high. We're worried about hyperviscosity and things like that. We don't have data for that. At least within patients who were studied, and who fit the eligibility criteria for the RISE UP study, it seems like this drug would be beneficial for just about anyone in terms of hemoglobin response. At least amongst those who have the hemoglobin responses, there seems to be some meaningful decrease in painful episodes like fatigue. The question is, if we have the next generation pyruvate kinase activator, might that do even better? Right? Not just with regards to hemoglobin response, but with regards to effect on pain and so on and so forth. I think there's some good lessons we can take from this, but it doesn't answer all the questions, it still needs some more work. Yes. I think we're moving into an era of combined therapy. The way I'm sort of setting that groundwork for my patients is to just draw them into the fact that despite single-agent modification therapy that we've had now for over 30 years, we're still seeing this progression towards end-organ failure. There have been massive benefits in the short run, but we realize that the disease modification has not been good enough to give us the outcomes that we want to see. That's why I'm excited about these results from the RISE UP study, is because I can see the data showing benefits now, with improvements in hemoglobin, decrease in hemolysis, the fatigue scores that we're seeing, decrease in transfusion burden that we've already talked about, that is clinically meaningful. The hope is that we can take the lessons we've learned from the disease, and we can expect, but we'll still have to watch, but we can expect that we could see improvements in organ function related to the results that we see now. We have to monitor over time. We're watching for those benefits. We have those patients right now that have hyperhemolysis, that fit within that phenotype, that despite hydroxyurea use, they maintain low hemoglobin. They don't have high frequency of pain many times. They're not in the hospital all the time, but we know they develop those downstream complications, significant pulmonary hypertension, early death, related to respiratory and cardiac causes. We have reason to believe that from data that we're seeing come out of RISE UP, reduction in hemolysis, improvement in anemia, could lead to very beneficial changes in our patients in the long term in terms of their organ function as well. Again, I'm excited about the idea of options, something that we can add. We know the data from the RISE UP trial showed that the mitapivat was safe when taken with hydroxyurea, that's crucial. In fact, over 70% of the patients were on hydroxyurea at the time they were on mitapivat, I think that that's crucial. It can be used single agent or combined with hydroxyurea, that's going to be critical to our patients moving forward as well. Dr. Anderson, after a period of a lot of stagnation in sickle cell disease, we're really living in a time where there's been just an explosion of advancements. Whether it be PK activators, mitapivat, etavopivat, tebapivat now coming, or really any other mechanism. I'm curious how you think about this sort of upgraded toolbox that you're going to have as a clinician in your lifespan clinic. Where is sort of your mind? What are you looking for in this toolbox? How do you sort of approach the future of sickle cell disease when it comes to improving care? That's a great question. I think that patients are hungry for options. For far too long, they've had one daily disease-modifying therapy, with hydroxyurea, which has had huge effects in terms of improvement in outcomes. They have still been dealing with the chronic complications of the disease, that they've been very excited about potential new options. I think that we're starting to see several different mechanisms of action that are very exciting. PK activation, as we've been talking about, is extremely exciting. I'm loving to see these first results coming out of phase III trials. In terms of PK activation, we're excited about the future of fetal hemoglobin induction and where we may see additional agents that could improve fetal hemoglobin even on top of hydroxyurea. We've also seen some frustration within the community regarding agents. We've had the removal of voxelotor from the market, that there were patients that were seeing benefit, that were frustrated. There were others that just didn't understand what was happening and had to do a very quick crash course in the way trials run and the understanding of that was difficult for the patient population. I think that what we will be seeing over the coming years is that patients are very hungry for options. They want to see individualized care. They want to be able to try things just like you can in diabetes and in heart disease and in other chronic illnesses where they see options, and they have not had that in the past. I, as a clinician, seeing the patients every day, I want to see options. I'm excited about what we're seeing come out of RISE UP. I'm also very excited to see data that is going to be coming out over the coming year that may give us a glimpse into what the future landscape is. Just as sickle cell disease is not a homogeneous disease, there are various variant genotypes. Within those genotypes, there's different other genetic factors that can change the phenotype for that individual. We're going to see that patients need different options. They're going to go on one for a while, and they may say, "That one didn't work as well for me. Let me try this mechanism of action now." We are going to be able to listen to the patient, to be able to have a discussion with them at the bedside where we can offer new potential therapies and work with them on an equal playing field to be able to figure out what works best for them. I'm excited about options. I think that's always the best-case scenario for the patient. Thank you, Dr. Anderson and Dr. Ataga, for joining us today for this discussion. I'll now hand the call over to Tsveta to highlight how the new mitapivat data presented at the 2026 EHA Congress reinforce our commercial positioning in thalassemia and sickle cell disease. Thank you, Ahmar, thank you, Dr. Anderson and Dr. Ataga, for sharing your perspectives on mitapivat and the sickle cell disease landscape. Our commercial organization is focused on two priorities this year. Continuing to execute and scale the U.S. commercial launch of AQVESME in thalassemia and preparing for a potential future launch of mitapivat in sickle cell disease. The data presented at the 2026 EHA Congress positions us well against both. Let me start with thalassemia. AQVESME is off to a strong start in thalassemia, with 242 prescriptions written as of March 31st by REMS-certified physicians. Early demand has been supported by efficient REMS onboarding and shorter than expected time to treatment, even as we continue to plan for an average 10-12 week initiation timeline. From here, our focus is on broadening prescriber reach across community and academic settings and expanding adoption in non-transfusion-dependent patients, who represent roughly two-thirds of diagnosed adults. As Sarah highlighted, we are presenting two important analyses from the ENERGIZE trial here at EHA, focused on the non-transfusion-dependent population. The data reinforce the commercial opportunity in two key ways. First, durability. In the open label expansion, the mean duration of hemoglobin response more than doubles with continued treatment, supporting sustained disease control and long-term patient persistence on therapy. Second, breadth. Responses observed in patients with higher baseline hemoglobin levels support the opportunity to treat earlier in the disease course, expanding the addressable population across a broader range of disease severity. Taken together, these data strengthen our confidence in the durability and broad applicability of AQVESME and in our ability to expand adoption over time as we continue to build and communicate its value within the medical community. I'm proud of the team's execution and encouraged by what these results could mean for patients living with non-transfusion-dependent thalassemia. As you saw earlier, the RISE UP phase III data highlight mitapivat's strong anti-hemolytic profile, directly addressing hemolysis, a core driver of both disease burden and mortality in sickle cell disease. We believe this profile underpins a compelling opportunity with a clear right to win on behalf of patients. From a market perspective, there are approximately 75,000 diagnosed patients aged 16 and older in the U.S., with roughly 25,000 actively treated or in need of therapy. We also believe the treated population can expand over time as new market entrants drive greater disease education, awareness, and engagement. Our initial launch is focused on the patients with hemolytic profile, a defined patient segment with a known prescriber base, which we have begun to map and prioritize. We see that as a focused entry point with the opportunity to expand over time. Our confidence in our ability to achieve commercial success comes down to three factors. First, experience. Mitapivat has the potential to be the first PK activator in sickle cell disease and could represent our third hemolytic anemia indication following PK deficiency and thalassemia. Many of these prescribers are already familiar with the molecule, and mitapivat is supported by more than 1,300 patient years of data, providing the kind of clinical foundation that supports confidence in this setting. Second, clinical differentiation. Beyond any single study, mitapivat is backed by a substantial body of evidence across three hemolytic anemia, supporting a proven clinical profile and consistent hemoglobin benefit. Third, our commercial foundation. The rare disease infrastructure and patient support capabilities we have built in thalassemia and PK deficiency position us well and gives us a platform we can scale appropriately to support sickle cell patients as we move forward. Taken together, we believe mitapivat brings the right combination of targetable opportunity, clinical depth c ommercial readiness to support a successful entry in sickle cell disease. To build from that initial launch focus over time. With that, I will hand the call back to Brian for his closing remarks. Ultimately, execution is what brings our strategy to life. Over the past year, we have activated the thalassemia market with a high-quality U.S. commercial launch, delivered key clinical and regulatory milestones with speed and precision, maintained disciplined operating expenses while investing for growth, and we've expanded our pipeline with strategic precision, most recently with the addition of cevidoplenib. This consistent execution underpins our confidence in the company's path forward. We remain laser-focused on delivering against our 2026 strategic priorities. Of key importance is continuing to drive a strong U.S. commercial launch of AQVESME and thalassemia. We'll share updates on launch progress with our second quarter results. I am extremely pleased with the team's execution as we sit here today. I'm also encouraged by the positive reception we've seen from the thalassemia community. We're advancing mitapivat in sickle cell disease and look forward to hearing from the FDA shortly on acceptance of our mitapivat sNDA. We look forward to the phase II sickle cell top-line data for tebapivat in the coming months. We'll continue to advance our maturing pipeline. Today, we announced the progression of AG-236 in PV to late-stage development following a successful phase I trial in healthy volunteers. Additionally, we'll have phase I proof of mechanism data for AG-181 in PKU patients before the end of the year. We were pleased to recently announce the addition of cevidoplenib, a next-generation SYK inhibitor for the treatment of ITP. Here we see a potential $1 billion non-risk adjusted peak year U.S. sales opportunity and look forward to updating you as we progress towards phase III initiation. What you're seeing here is the evolution of Agios into a multi-mechanism, multi-asset company with strength and breadth of rare disease capabilities. We built a leading position in PK activation with broad clinical validation across hemolytic anemias and a deep data set supporting durability and safety. At the same time, we are intentionally diversifying our approach, bringing forward complementary programs, including SYK inhibition in ITP and additional genetic and metabolic targets beyond hematology. Each of these programs fit within a focused and disciplined strategy, targeting well-characterized biology and meaningful areas of unmet need. As we look ahead, we're not just advancing individual assets, we're building into a sustainable leadership position in rare hematology with the capability to extend that leadership into other rare diseases over time. Today, our pipeline represents the potential to bring forward transformative medicines in markets totaling over $10 billion in 2030. Thank you for joining us. With that, we're pleased to open the call for Q&A, where we'll be joined by Dr. Anderson and Dr. Ataga. Operator, please open the line. Thank you, sir. As a reminder, to ask a question, you will need to press star one one on your telephone. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. I show our first question comes from the line of Andrew Berens from Leerink. Please go ahead. Hi, thanks, congrats, Brian and team, on the progress on the preliminary session at the meeting. Just a question on the label. Do you think the potential label could be for the accelerated approval would reflect the RISE UP trial population, or is there a chance it could reflect the confirmatory trial population? Just trying to get a sense for how we should consider the addressable population. Then maybe similarly, you have two different brands now for mitapivat. What's going to go into the decision about which one you would use for sickle cell? Thanks, Andy. I'll have Sarah start with the label. I think it's a good opportunity to explain the role of RISE UP in the label and then the importance of the confirmatory study as well. Sarah, you want to start there? Sure. Thank you. Thanks, Andy, for your question. As it relates to the label, the RISE UP data is the package which we filed. In the clinical trial section, you will always see the RISE UP clinical trial being reflected in that label. The confirmatory trial for us is a way to further confirm benefits that we now have observed in the RISE UP trial. At the time of when that data package would be available for review, when we submit that part, that clinical trial population would be added to that section of the label as well. First label, RISE UP trial, as the label evolves, next trial gets added. That's great. The second part relates to the two different brand names and how we think about that. Yes. For the brand names, we have PYRUKYND and AQVESME, as you know. These two brand names basically give us optionality. It will be a matter of review, ultimately, which brand name gets chosen. For us, we feel very ready and prepared in either scenario. We now know, based on the data that Tsveta's team has generated with the thalassemia launch, that the team would be ready to launch with a win. That being said, I'm going to repeat that the safety profile of the drug is favorable. We see an option after the go. Okay. Thank you, and congrats again. Thanks Andy. Thank you. I show our next question comes from the line of Eric Schmidt from Cantor. Please go ahead. Thanks for taking my call and appreciate all the information this morning. This morning, New York time at least. Maybe one on AG-236 and the decision to take that forward into later-stage studies. I'm not sure who's best to answer this. Can you talk a little bit about what you think is the unmet need in PV? Then, of course, this isn't the only TMPRSS6 targeted therapy. There are other modalities in development. Can you speak to how you think this is going to be differentiated from others, including, I think, some that are more advanced? Thank you. Yeah. Thanks, Eric, and I will say good morning. I'm glad you asked about AG-236. We're excited about the opportunity. I think this is yet another disease, polycythemia vera, that is really in need of being disrupted on behalf of patients. It's exciting that there are different modalities being pursued. In our case, we're quite excited about the TMPRSS6 inhibition pathway. Maybe, Sarah, you could talk a little bit about what the overall target is as we look ahead towards more advanced development. Yeah. We're very excited about our AG-236 assets. Based on the healthy volunteer data that we now have, we really see the potential for best in class in polycythemia vera and so are looking forward to move it forward into patients living with this disease. We believe that based on the data that we now have, that there is really an opportunity to extend the dosing frequency up to six months in between doses, and that that would allow for very durable and maintained hematocrit control. We really see that as a major advantage to the field. Eric, I'll just say in this case, too, I draw a bit on my own experience in hemophilia, and we saw similar dynamics as different modalities evolved in hemophilia, where you went from significant frequency of dosing, which is difficult for patients chronically, to then longer intervals of therapy that really maintains the durability that patients look for. Again, it's a pretty important step that we see to now have the healthy volunteer and data which looks compelling and the opportunity to move forward. Thank you very much. You're welcome. Thank you. I show our next question comes from the line of Samantha Semenkow from Citi. Please go ahead. Hi, good morning and good afternoon as well, thanks for taking the question. I have two, one for the physicians on the call and one for management. For the physicians, in the fireside chat portion, which is very helpful, you mentioned how important reduction in transfusion burden is. I'm wondering if you could just contextualize that a little bit further and talk about the magnitude we're seeing out of the RISE UP data and how impactful that is in your views. Then for management, I'm not sure if you've done this analysis, but was there any correlation in the patients that achieved a transfusion burden reduction with also seeing a reduction in pain crises, fatigue, or hemoglobin improvements? Thanks very much. Thanks, Sam. Let's take the opportunity to have both of our KOLs comment on your first question about the reduction in transfusion burden and the magnitude of that reduction that we saw in RISE UP and the meaningfulness of that. We'll start with Dr. Ataga and then go to Dr. Anderson, and then Sarah can comment on your question about the correlation. Dr. Ataga, do you want to start on that? Yes. Thank you for the question. With regards to transfusion, that's something that happens relatively frequently in patients who have sickle cell disease. Patients can get transfused when they have acute complications. For example, when they have acute pain episodes or what we call acute chest syndrome, or when they have strokes, or they could get transfused chronically, which means that they have repeated episodes of transfusion perhaps every month going forward. The problem with transfusion is that when patients get transfused a lot, it can be associated with a variety of risks. There is the risk of infectious complications, which is not very common in the U.S., but it's not zero, right? Patients can have a variety of infections. HIV infection is a possible risk. Hepatitis infection risk. More commonly is the fact that patients can have problems like what we call iron overload, because when you give red blood cells, red blood cells have hemoglobin in them that has iron. Over time, that can accumulate, and accumulated iron levels can cause organ dysfunction as well. That becomes an additional burden for patients with sickle cell disease. Another problem that we see with repeated transfusions in patients with sickle cell disease is that they can have this problem called red blood cell alloimmunization. That means that these patients actually have antibodies that makes it more difficult for them to get subsequent blood transfusions. The benefits of mitapivat in patients who have hemoglobin responses, as we see in post-hoc analysis now, shows that we can reduce this transfusion requirement and potentially reduce these complications, including iron overload, risk of aggravation, and things like that. That's very exciting to see. That's great. Dr. Anderson, anything you'd like to add? I'll just say, I agree with everything that Ken said. I think our patients, what I've seen as a lifespan physician is I see that transfusion burden starting in pediatrics, the iron buildup starting at that point, just rising over time. This clinically meaningful decrease in transfusion that was seen in the trial in the responders, I think is significant to the patient population. We can't lose sight of the fact that every reduction in a transfusion time point for an individual affected by the disease means potentially two visits that they don't have to come to a center. There's a visit. Our patients typically require their blood to be typed specifically for them on average about 48- 72 hours prior to their transfusion because of the need to get very specific units so they don't develop alloimmunization over time. Oftentimes patients will come in for labs 48, 72 hours before, then they come back to the clinic for transfusion. I think that the transfusions have a significant impact on quality of life for patients. That's on top of all the other risks associated with transfusion, with iron, alloimmunization, infection, and other things like that. I think it's very exciting data showing reduction in transfusion in patients where it's been very difficult to reduce transfusion burden historically. Well, thank you very much. I must say it's great having both of you on the call so we can hear the questions and get a real response from both of you. Sarah, then there was the second question from Sam about is there any correlation between transfusions and I think she'd asked about the pain, for example. Yeah. Sam, this was an overall population analysis that we've done looking at the transfusion burden in mitapivat versus transfusion burden in placebo to go in line with the improvement in hemolytic anemia that we saw in the overall patient population. I do want to stress what the two physicians actually just highlighted, the importance of reducing transfusions just because of the risk and the impact to the patient population. We hear that sentiment when we now present the REIGNITE trial, the phase III confirmatory trial, to physicians who participate with their center, that there's a lot of enthusiasm for that trial because of all of the reasons that were just highlighted by Dr. Anderson and Dr. Ataga. Thank you. I show our next question comes from the line of Gregory Renza from Truist Securities. Please go ahead. Hey, guys. It's Aneesh on for Greg. Thanks for all the color this morning and for taking our questions. Just a couple from us. On the RISE UP data, the hemoglobin response was clearly rapid, separating from placebo by week two and holding through week 52, as you remarked on. I'm wondering how you're thinking about leveraging that rapid onset clinically. Does it lend itself to a trial of therapy or a treat to target approach where you can identify non-responders early? On the theme of responders, just if you could help frame any leading indicators from baseline characteristics you've seen that would help predict whether or not a patient is likely to be a responder and thus fit into the important responder findings we've discussed today. Thanks so much. Thanks, Aneesh. Both of those are good ones for Sarah to answer. Well, yes, indeed. You could see in the data that the hemoglobin responses were observed rapidly. As Dr. Andemariam has highlighted, that week two is the first measurement we take within the trial, and that's where you start seeing the separation of the lines. That being said, I hope people also have an opportunity to look at the thalassemia data in which we see that, yes, you have a lot of great response early on, but some people continue to evolve their response along the way. Now in the thalassemia data, actually, the response rate went up to 60% with prolonged exposure. This is why it's important to continue to follow patients in the extension study to understand up to how long one can expect a hemoglobin response to arrive. In regards to the baseline disease characteristics that were, is there anything that can predict who is going to respond? Again, as Dr. Andemariam highlighted in the presentation, we really looked at pre-specified a lot of factors to look at to try to determine who would respond versus who would not respond. There is nothing that actually pops out that proactively can predict who is going to have a response. That is, again, very consistent with what we've observed in the thalassemia and in the PKD patient population. Therefore, we do anticipate that this is more going to be around patients try the drug, there will be an assessment of over a couple of weeks to months of is this actually working for the patient, yes or no, then decisions can be made by the physicians and the patients together on what is the best course of action. We've heard that consistently since November, actually, when we did the top line release of the RISE UP data, we heard a lot of both thought leaders as well as community physicians comment on the fact that the safety and tolerability really reinforces this try first dynamic, which is a really important opportunity. Thank you, Sarah. Thank you. Okay. I show our next question in the queue comes from the line of Emily Bodnar from H.C. Wainwright. Please go ahead. Hi. Thanks for taking our question and congrats on the progress as well. One on the transfusion version data. Can you kind of help us understand the differences between the total RBC units transfused, which didn't look too different from placebo, compared to the average RBC units transfused, which was clearly more significant? For a second question, given the confirmatory trial is lowering the age to 12 from 18, can you discuss how much you would expect that to increase the addressable patient population versus RISE UP and unmet need in adolescents versus adults? Thanks. Thanks, Emily. Sarah, do you want to comment first on the transfusion aspect, the total? I think the question is about total RBCs. Emily, when you look at the data of the RISE UP patients, we actually see positive effects for however we look at the red blood cell units transfused, both meaning the frequency plus the red blood cell units. The totality of the data shows that it is very consistent, pointing towards favoring mitapivat. The other thing here is for RISE UP, when you're saying the overall red blood cell units transfused, this was not a heavily transfused patient population, right? This is not a chronically transfused patient population for stroke prevention or something like that, just as it occurred clinically. That's where we did see these great results. As mentioned also in the remarks, these results were stronger than hydroxyurea results. We feel very confident about where we are going with this confirmatory trial. Sarah, comment on the confirmatory trial age reduction actually to 12 and older and the importance of that opportunity to the overall population and commercial opportunities. Absolutely. Emily, we provided some information on the population as it currently stands. As a reminder, our label, the initial label, potential label, will be based on the RISE UP data, which is ages 16 and older. In the U.S., there are about 75,000 patients with sickle cell disease that fits the patient population. We have further refined that looking deeply into the claims data and identified about 25,000 patients who are either being treated or have been previously treated and are in active care for sickle cell disease, which gives us an initial kind of clarity of where we should focus our launch preparation and efforts. We're super excited about the opportunity through the confirmatory study to actually study the product and provide data in the younger age group of 12 and older. As that data kind of gets added to the label over time, I think it positions us very well to move into that broader patient population and bridge the gap towards the 100,000 patients that are living with sickle cell disease in the U.S. Great. Thanks, Emily. Thank you. I show our next question comes from the line of Salveen Richter from Goldman Sachs. Please go ahead. Hi, this is Lydia on for Salveen. Thanks so much for taking our question, and congrats on the updates. Maybe just another for the two physicians on the call. Could you just speak to what percentage of your sickle cell patients receive transfusions regularly? Looks like it was around 25% of patients in the RISE UP study. Is this more or less reflective of the overall population? Thanks so much. Thanks, Lydia. Let's send it to our thought leaders on the line. This time I'll reverse the order. Dr. Anderson, do you want to start with the percentage of your patients that receive transfusions? Just reinforcing the point that Sarah made, this is to match the confirmatory trial. It's really about episodic transfusions. Correct. I would say in my population, it's about 10%, maybe a little less than 10%, that are receiving transfusions for therapy, meaning that they're on a recurring basis of transfusion schedules because of a certain indication. The majority of those are historical individuals who've had either stroke or have had an abnormal transcranial Doppler ultrasound showing increased stroke risk. They're in recurring transfusions for that. I think what this data speaks more to would be those patients that are receiving transfusions because of some acute complications or because of symptomatic anemia potentially leading to some of the early signs of organ toxicity that we see in our adult patients, like renal insufficiency. We have a much larger group that are receiving enough transfusions scattered throughout each year that they are developing significant iron overload. On the adult patient side, we see diminishing returns from hydroxyurea, where patients that had been doing great with higher hemoglobin, those hemoglobin's are starting to decline, and they are needing more frequent episodic transfusions due to symptoms. In certain patients that are also needing erythropoietin add-back in combination with hydroxyurea in order to try to reduce transfusion burden. I think there's a significant portion of patients that are falling into that category where we would like to see the frequency of transfusions reduced and therefore the excitement around the data coming out of REIGNITE. Thank you. Dr. Ataga, before we just move on, maybe we'll have Dr. Ataga comment as well. Thank you. I do agree with Alan, just to add to that. I would say that when we transfuse patients, there are two ways in which we transfuse patients. Patients can get transfused episodically, and many times it's because they have acute complications. They come into the hospital because they are sick for whatever reason. Could be that they're having an acute pain episode or some other complication that can, what we call acute chest syndrome. Hemoglobin level goes down, and they get transfused, either for symptoms or for treatment of their disease complication. Patients can have what's called chronic transfusions. Typically, this refers to patients who get blood transfusions approximately every four weeks or so, three- four weeks. Many times it's something that's ongoing. For patients who get chronic transfusions, commonly it's for reasons like stroke prevention or because they've had an actual stroke in the past. It's for secondary prevention of stroke or other reasons. I would say that the numbers in my patient population are similar to what Alan talked about, between 5%-10% of patients get transfused. Among patients who get transfused episodically, that's much higher. I don't have the actual numbers in front of me, but I would say it's much higher, 30%-40%, 30%-50%, even higher than that. Patients that get transfused once a year or maybe less than that. Having data of a drug that decreases transfusion requirements in patients with sickle cell disease is obviously very exciting to be able to help to reduce complications linked to transfusions in these patients. Very helpful. Sarah? Yes. Thank you for both those perspectives. I think for us, from a clinical trial perspective, we're really just looking at the transfusions as an endpoint to further confirm and measure clinical benefit for the improvements we now have seen in the RISE UP trial for the anti-hemolytic effect that we've seen, the improvement of hemolytic anemia overall. We're excited to embark on the REIGNITE trial. Thank you. I see our next question in the queue comes from the line of Tess Romero from JP Morgan. Please go ahead. Good morning. Thanks so much for this presentation, Agios team, and to the doctors as well for sharing their insights. I think one of the KOLs touched on this earlier. In the context of what you know today around mitapivat's potential in sickle cell disease, what do you think you need to see for tebapivat to move this program forward? Is there a threshold on hemoglobin response that would trigger you to say, "This could materially improve the profile that you're seeing with mitapivat, and I want to move this into phase III?" Thanks. Thanks, Tess. Maybe we'll start with Dr. Ataga, and I'll just phrase the question as generally what's on your wish list for continued progress? Of course, to remind everybody, we have tebapivat, our next-gen PK activator, and we're looking forward to the phase II sickle cell data in the second half of this year. Dr. Ataga, perhaps you could start by just commenting on what else you'd like to see. Thanks for the question. I would say that the data for mitapivat is quite exciting. Obviously, we can always do better, right? I would say that with tebapivat, a couple of things. For one, that drug seems to be administered once a day. If you have a drug that's taken once a day compared to a drug that's taken two times a day, most people would prefer that. The likelihood of missing doses is less. I think that's an advantage to that. If the results of the available data confirm that tebapivat has this impact on having a higher hemoglobin response. That may also be a good thing. Not only might there be a higher hemoglobin response. Patients have higher responses in terms of hemoglobin. That might also translate into decreased complications such as painful episodes, improvements in fatigue scores in patients with sickle cell disease. That hemoglobin response may also translate into improved clinical benefit for patients with sickle cell disease. We'll have to see what the data show. I think potentially, if it does what we hope it does, tebapivat might be more convenient in terms of administration to patients, and then might have even better hemoglobin responses and decrease in complications such as pain and improvements in fatigue. Okay, thanks. Dr. Anderson, what I'll do is have Sarah comment on, of course, what we're looking for in terms of continued development. Dr. Anderson, maybe you could comment as well? Sure. Yeah, I think that what we'd be looking at would be the further improvement in hemoglobin. What we're seeing come out of gene therapy results is that as you near normalization of hemoglobin and you have the decrease in all these hemolysis parameters, you see that many of the complication symptoms that are occurring in patients start to go away. I think that the further increase in hemoglobin, I'd like to see even further normalization of the hemolysis markers as well, bilirubin, retic, LDH. Seeing the downstream effects of that. Hopefully reduction in VOC that's clinically significant across the patient population, I think would be also very critical to see in the future as well. Yes. Thank you both. I think you guys summarized it perfectly because now we know, of course, from the RISE UP trial that hemoglobin response, once we have hemoglobin response, it drives a lot of the other benefits that we can observe in the sickle cell disease patient population. That's indeed what we're hoping for, that tebapivat can deliver more hemoglobin responders or a higher hemoglobin response because we do now understand based on the RISE UP data that that is really important to drive all of these additional benefits. Just, now as you know, we've announced that we are anticipating data for tebapivat in the second half of this year, more to come. Thanks, Tess. Thank you. I share our last question in the queue comes from the line of Luca Issi from RBC. Please go ahead. Oh, great. Yeah. Thanks so much for taking my question. Maybe two quick one. Maybe Sarah, you obviously filed mitapivat for sickle cell disease almost exactly a month ago to this day, I think of May 12th. A 60-day clock is obviously ticking. Have you had any informal interactions with the FDA since you filed? Maybe bigger picture, how confident are you that the file will be accepted and do you expect standard or priority review? That's one. Then maybe second, Tsveta, on the commercial side, are you thinking about a scenario where you get approved on Accelerated Approval basis based on RISE UP, but your competitor maybe reached the market with full approval, obviously based on reduction in crisis. Do you think the docs and payers will favor your competitor, or do you think that everybody would look at these two molecules still as broadly similar given the same mechanism of action? Any thoughts there, much appreciated. Thanks so much, guys. Thanks, Luca. Sarah can start just with one clarification. We're talking about mitapivat. Then Tsveta can comment on the unmet need that exists and how we think about the commercial opportunity. Yes, thanks for the question. Yes, it's our mitapivat sNDA filing that we indeed announced about a month ago. We, of course, continue to engage with the agency along the way because we effectively filed at this point. That's really it. Maybe hand it over to you for the second question. Absolutely. I think we heard it from the KOLs there, and it's very consistent with what I hear interacting with physicians right now here at the meeting at the moment as well. The sickle cell disease is a disease with a high unmet need and very limited treatment options still. The opportunity to have multiple products on the market is a huge advantage across the board. We don't know much about the trial data, but what we know, especially now and the broader perspective of the RISE UP data has been presented. We know that it really resonates with the treating physicians from the perspective that the hemoglobin improvement can lead to downstream benefit for patients, both in terms of quality of life as well as reduction in pain crisis. We'll wait to see how the data continuously evolve, but we think that the reduction of the modalities can be potentially linked in the future to reduction in the cumulative organ damage we've observed in these patients as well. We feel extremely good about our profile and opportunity for us to commercialize. Don't forget, this is our third potential indication in the hemolytic anemia. We have very strong and consistent hemolytic profile and a lot of safety accumulated not through the clinical studies, not only through the clinical studies but also in the market as well. We are getting ready for potential launch. Got it. Thanks so much. Thank you. That concludes our Q&A session. I would now like to turn the conference back to Brian Goff, Agios's Chief Executive Officer, for closing remarks. Thank you, Dylan, and thanks again to everyone who joined us today at the 2026 European Hematology Association Congress. We really appreciate your engagement and interest in Agios. Again, I want to say a special thank you to Dr. Anderson and Dr. Ataga for sharing their perspectives and their expertise on sickle cell disease and the potential role that mitapivat can have for patients. The data presented at EHA reinforced the consistency and durability of mitapivat's anti-hemolytic profile across both thalassemia as well as sickle cell disease. More broadly, these data highlight an important inflection point for Agios as we enter the next phase of our evolution, expanding mitapivat across multiple indications while building a broader multi-asset rare disease company with multiple mechanisms, programs, and opportunities to create value. We leave EHA confident in our path forward, executing the AQVESME launch, advancing mitapivat's sNDA in sickle cell disease, and continuing to build a differentiated pipeline with discipline, focus, and clear value drivers ahead. Thanks again, and we look forward to updating you on our progress along the way. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.