Agios Pharmaceuticals, Inc. (AGIO) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Agios Pharmaceuticals European Hematology Association 2026 Investor Webcast and Conference Call. [Operator Instructions] 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 Investors 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 derisking the PK activation platform in hemolytic anemias, which include 2 PK activators, mitapivat and our next-generation asset tebapivat. We've demonstrated that we can translate biology into clinical benefit. And 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 to 24 months. From our continued scaling of the U.S. commercial launch of AQVESME in 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 1 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-TMPR6 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. And 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 6-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. And 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 from mitapivat across multiple hemolytic anemias, including 10 accepted abstracts and an oral plenary presentation of the RISE of 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. This data shows sustained and clinically meaningful hemoglobin improvements over time. In patients that continued on mitapivat into the open-label 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 gram per deciliter improvement from baseline in average hemoglobin over any 2 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 1/3 of prior nonresponders 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 grams per deciliter. Importantly, there were no new safety events that change our understanding of the safety profile of mitapivat in thalassemia. Another interesting dataset 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 grams 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 gram per deciliter or more hemoglobin increase. This was accompanied by a clinically meaningful improvement in fatigue with a 5.1 point change in facet fatigue scores based on lease 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 nontransfusion-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 effect of mitapivat across rare hemolytic anemias, including hereditary spherocytosis, hereditary serocytosis and congenital anemia type 2. 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 gram per deciliter during the fixed dose period 2. 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 dataset 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 antiemetic agent. Mitapivat demonstrated a 40.6% hemoglobin response versus 2.9% on placebo with responses maintained through week 52. Among responders, the mean increase in hemoglobin was 1.6 grams 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 effect over time. This consistency across multiple endpoints reinforces mitapivat's antihemolytic mechanism of action with aligned improvements across biologic markets. 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 fatigue, we observed directional responses favoring mitapivat over placebo across key measures of hemolysis and other sickle cell pain crisis-related end points. Importantly, hemoglobin response translated into clinically meaningful benefit across key disease outcomes in sickle cell disease. Compared to nonresponders, 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 dates for sickle cell pain crises. In addition, we see a clinically meaningful improvement in fatigue based on the promised fatigue measurement scale. These data reinforce that for patients who demonstrate the hemoglobin response on mitapivat, there is potential for downstream clinical benefits, 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 improvement across a number of other patient-reported outcomes. All of these measures, including pain, sleep and physical function, favored hemoglobin responders compared to nonresponders. 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 56% 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 showed 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 inform 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 4 through week 52. On the next slide, you can see the design of the REIGNITE Phase III trial intended to confirm clinical benefit of mitapivat in sickle cell disease. The REIGNITE trial is a 52-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 the fixed side. 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 1 packed red blood cell transfusion in the prior 12 months, baseline hemoglobin of 5.5 to 10.5 grams per deciliter and additional evidence of hemolysis to support a measurable treatment effect. What's most important in the RISE UP dataset is the consistency we're seeing between biology and clinical outcomes. Mitapivat delivers a reproducible antihemolytic effect across the overall patient population, which aligns with its mechanism. And in patients who achieved hemoglobin responses, those improvements translate into meaningful clinical benefit, including our 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 3 hemolytic anemias, an important consideration in a chronic disease like sickle cell disease. Taken together, we strongly believe mitapivat represents a differentiated antihemolytic 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 nontransfusion dependent populations including patient-reported outcomes, which is an important proof point. And in sickle cell disease, we're again seeing a consistent antihemolytic signal with hemoglobin improvements translating into clinically meaningful outcome in responders supported by a favorable safety profile. Therefore, across 3 distinct rare diseases, the data consistently shows that targeting red blood cell metabolism can drive both biologic and clinical benefit. 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. And 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, 2 leaders in the sickle cell disease care and research fields. Together, we're going to discuss the current burden of sickle cell disease, mitapivat and 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. And what I recognize coming from a pediatric background is that we were seemingly doing good work with 1 disease modifier with hydroxyurea in patients who were seeing the improvements in terms of reduction in stroke and pain events, decrease in the syndrome and some of those things. But what I now recognize wearing an adult hat is that the adults were still significantly struggling, not only struggling to find locations for treatment, but also struggling to limit the organ damaging effects of the disease over the life span and that single modification therapy is just not enough. And so 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 match counterparts without sickle cell disease. They lack options for disease modification and 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?

Yes, definitely. So the one thing I would add to what Alan has said is the fact that sickle cell, this is very heterogeneous, right? So within patients and between patients, they can have severity of disease at And we also know that as patients get older, they have this cumulative progressive organ damage. So I remember a few years ago, there was some controversy locally because someone had said something to the fact that we take good care of children and then the outside and die, which was missing to that adult providers is not do a very good job, right? I don't think that's what that provider meant like that's sequence. But it just kind of shows the fact -- illustrates the fact that special Escape already have this cumulative and progressive organ dysfunction, which increases the risk of dying. And so it just tells us that we need to do more work to try and improve the care that provide pressure with sickle cell disease, prevent complication from developing, help them to lead better quality lives and survive for much longer.

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 kind of 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.

So 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. And everybody is moving along that pathway in some degree. And so what I wanted to really draw my patient towards is that that damaged red cell that's dying to quickly is leading to all the downstream complications. And that is that that fast turnover of the cells that's leading to the chronic anemia. And so 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 improve. And 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 improve. They're so used to having the fatigue, having this inability to do the things that they want to do. And so asking the right questions to really tease out what is it you want to see improve? And how can we showcase that this is related to the chronic hemolysis and anemia that you've experienced. And 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 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.

Yes. So I think it's important to understand that much of the problem we've seen patients with sickle cell disease are driven by right, as well as hemolysis not just what. So there's significant overlap in terms of to public to project with sick cell disease. And so -- it's not that 1 problem is caused purely by hemolysis and one is caused purely by but this is actually interact. But lots of studies also show significant relationship between hemolysis, anemia a variety of complications syncretic services. So we know that anemia is bad. It doesn't not other have sickle cell disease or not, right? But it's particularly bad in patients who have sickle cell disease. So like Alan said earlier, so there's lots of studies that show associations between anemia and lots of products. So increased mortality in these patients and organ dysfunction. So increased risk of stroke, for example, the patients who might have hypotension, kidney disease and so on and so forth. So drives lots of things, fatigue and all of that. So I think what we haven't really shown in a prospective manner is the fact that if we are able to fix this problem that we can actually mitigate or prevent these problems from developing, right? Intuitively, it would seem like that, but we need to kind of prove that, right? And 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'll productively prevent progress. I think where we have shown that somewhat is the case of patients who have abnormalities of and patients who have children who had higher an adult so I don't really treat. I don't get pistols myself. But in the recent, we lead that transfusion therapy does help to decrease the risk of and there's also data for the use of hydroxyurea, which might work at least in part from increasing hemoglobin levels in these patients as well. So I think now that we're having therapies common board that seem to have more robust effects on hemolytic anemia, right? We might see even greater benefits in decreasing or perhaps preventing some of these complications. So we need to do the studies going forward and see what we think happens actually growth.

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. So that's a good question. And that's a discussion we have a lot as sickle cell doctors, right? So I think -- so for one, most of the big studies in sickle cell disease are focused on vaso-occlusion painful crisis as the primary endpoint, right? And that's not particularly surprising because this is the most for see patients, right? And so that's -- most of the studies have focused on this endpoint. And many of these studies have not been successful trying to address this endpoint as well. And many who have speculated or suggested that maybe we should stop looking at painful crisis as an endpoint because as many of these studies have not been positive. But I don't think we can ignore it. I think what we need to do is always 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 subjected in terms of pain, right? And we don't have any biomarkers that can tell us that someone is having pain or not, right? So it's not like there's some test you can do that tells your patient is having pain or the pain has resolved. I think there's a right of way the definition can be improved because it's problematic, right? So when we look at the current definition of painful crisis, it's confounded by a variety of factors, right? So for one, if I'm citing of patients getting opioid and the partners of use of complete different depending on where you live in the world, right? If you live in Memphis, Tennessee, where I live, compared to a patient who lives in Mali or in Code d'Ivoire or in Nigeria and 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 in -- on the continent of Africa, where I have seen 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 and everyone, every time they touch the health system, and we sort of conditioned individuals to have as much as close to 0 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. And 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 that -- 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?

So I think this was a very important study. that showed for one large group of patients across the world pretty much global study looked at patients in the U.S., in Europe, in South Saharan Africa, that treatment with mitapivat, which is this kinase activator increases the likelihood of patients have in what's called the hemoglobin response in a large number of patients. So we grew about 40% of patients had hemoglobin response, in which the hemoglobin went up by at least 1 gram when you compare them from baseline asset between 24 and 52 weeks compared to patients who got placebo. So the study did not show any significant differences between patients who got the active medicine and placebo with regards to an rate of pain episodes. But in those patients who had a hemoglobin response, there did seem to be a meaningful decrease in the frequency of pain in these patients.

So 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. So 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. And our patients want to see that. They want to see that if they start something that they're seeing the benefit of that in the trial results, seeing that happening in the first 2 weeks of treatment without first CBC time point. The other thing that we want to see in a trial like this is the durability of hemoglobin response. So seeing that hemoglobin rise greater than 1 gram per deciliter and then maintaining over that in the trial results showing between week 24 and week 50 durability of that hemoglobin response. So all those things are very exciting. I think as well the tolerability that was seen in the results. So 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 and thalassemia, and 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. And so I think that patients are wanting to see that the results have held up over time and in this case, in different disease populations. And so 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 aluminization and other things where we need to try to reduce the need for transfusions. And then 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 are responding. And my hope is that we'll see that play out with this type of a therapy in the future as well.

So just to follow on to that. When you think of the RISE UP data, Dr. Ataga, what what patients do you believe are most likely to benefit from mitapivat? How do you -- how are you thinking about where mitapivat sort of places itself in the clinical context?

Yes, so that's a good question. So from the RISE UP study, everyone seemed to benefit, right? So when we look at the subgroups, whether that is based on age, whether that is based on genotype, based on hemoglobin levels, to have adequate benefits Having said that, there were eligibility criteria to study. And so patients had to have hemoglobin levels of between 5.5 and 10.5. And so the question is if you have someone who has a hemoglobin of 11 or 12, is that someone you should constantly put a drug like the So it's not very clear, right? You don't have detailed support that. So we as sickle cell doctors always get worried when the hemogram level goes too high. I worry about like that. So we don't have data for that. But at least within patients who are studied and hope there's cite for the RISE UP study, it seems like this drug would be beneficial for just about any one in terms of hemoglobin response. And at least amongst those who have hemoglobin responses, there seems to be some meaningful decrease in painful episodes like fatigue. And so the question is if we have the next generation might that do even better, right? So not just what you get to hemoglobin response, but with regards to its effect on pain and so on and so forth. So I think there's some good lessons we can take from this, but it doesn't answer all the questions, just still needs more work.

Yes. I think we're moving into an era of combined therapy. And that 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 realized that the disease modification has not been good enough to give us the outcomes that we want to see. And so 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. And then 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. So we have to monitor over time. We're watching for those benefits. But we have those patients right now that have hyperhemolysis that are -- 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. And so 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 the organ function as well. So 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, and that's crucial. And in fact, over 70% of the patients were on hydroxyurea at the time they were on mitapivat. And so I think that, that's crucial. It can be used single agent or combined with hydroxyurea. So 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 activator, 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 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 a huge effects in terms of improvement in outcomes, but they have still been dealing with the chronic complications of the disease that they've been very excited about potential new options. And so 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 voxelator from the market that there were patients that were seeing benefit, they 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. And so that was difficult for the patient population. And so 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 other chronic illnesses where they see options, and they have not had that in the past. And so I, as a clinician, seeing the patients every day, I want to see options. So 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. And so we're going to see that patients need different options. They're going to go on 1 for a while, and they may say that one didn't work as well for me, let me try this mechanism of action now. And so 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. So 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, and 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 2 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 31 by REM-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- to 12-week initiation time line. From here, our focus is on broadening prescriber reach across community and academic settings, and expanding adoption in nontransfusion-dependent patients, who represent roughly 2/3 of diagnosed adults. As Sarah highlighted, we are presenting 2 important analysis from the ENERGIZE trial here at EHA, focused on the non-transfusion-dependent population. The data reinforce the commercial opportunity in 2 key ways. First, durability. In the open label expansion, the mean duration of hemoglobin response more than doubled 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 supports 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 nontransfusion-dependent thalassemia. As you saw earlier, the RISE UP Phase III data highlight mitapivat's strong antihemolytic 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, age 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 non-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 3 factors: First, experience. Mitapivat has the potential to be the first big 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 3 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 the 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 and commercial readiness to support a successful entry in sickle cell disease and to build from that initial launch focused 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 sevedoplinib. 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 in thalassemia. We'll share updates on launch progress with our second quarter results, and 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 and we look forward to the Phase II sickle cell top line data for tebapivat in the coming months. Next, 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. And finally, 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 nonrisk-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 dataset supporting durability and safety. At the same time, we are intentionally diversifying our approach, bringing forward complementary programs, including SYK inhibition and 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. And 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.

[Operator Instructions] And I show our first question comes from the line of Andrew Berens from Leerink.

Congrats Brian and team on the progress on the culinary session of the meeting. I guess a question on the label. And 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. And then maybe similarly, you have 2 different brands now mitapivat, what's going to go into the decision about which one you would use for sickle cell?

Yes. Thanks, Andy. I'll have Sarah start with the label. So 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. So Sarah, do you want to start there?

Sure. Thank you. Thanks, Andy, for your questions. So as it relates to the label, so -- the RISE UP data is the package which we filed. So in the clinical trial section, you will always see the RISE UP clinical trial being reflected in that label. The confirmatory trial for us a way to further confirm benefits that we now have observed in the RISE UP the trial. And then at the time of when that data package would be available for a review, then -- when we submit that part, then that clinical trial population would be added to that section of the label as well. So first label, RISE UP trial, then as the label evolves mix trial gets added.

That's great. And then the second part relates to the 2 different brand names and how we think about that.

Yes. So for the brand name, so we have and as you know. So these 2 brand names, basically give us optionality. It will be a matter of the view, ultimately, which branding obviously gets chosen. But for us, we feel very ready and prepared in either scenario. And we know that our -- we now know based on the data that has generated with the thalassemia launch would be ready to launch that being said, I'm going to repeat that the safety profile of the drug is favorable, so we see a

And I show our next question comes from the line of Eric Schmidt from Cantor.

Well, 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. But can you talk a little bit about what you think is the unmet need in PV? And then of course, this isn't the only temporary 6 targeted therapy or much of other modalities in development. Can you speak to how you think this is going to be differentiated from others, including I think more advanced?

Yes. 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. And it's exciting that there are different modalities being pursued. In our case, we're quite excited about the inhibition pathway. Maybe, Sarah, you could talk a little bit about what the overall target is as we look ahead towards more advanced development.

Yes. And so we're very excited about our AG-236 assets. Based on the data that we now have, we really see the potential for in polycythemia vera and so we're looking forward to moving 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 6 months in between doses and that, that would allow for a very durable and maintain hematocrit control. So we really see that as a major advantage

And then, Eric, I'll just say in this case, too, I draw a bit on my own experience in hemophilia, and I saw similar dynamics as different modalities evolving hemophilia where you went from significant frequency of dosing, which is difficult for patients chronically to then longer intervals of therapy that really maintains that durability that patients look for. So again, this is -- 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.

And I show our next question comes from the line of Samantha Semenkow from Citi.

I have 2, 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? And 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 was also seeing a reduction in pain crisis fatigue or hemoglobin improvements?

Thanks, Sam. So 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. And then -- and we'll start with Dr. Ataga, and then go to Dr. Anderson and then Sarah can comment on your question about the relation. So Dr. Ataga, do you want to start on that? .

Yes. So thank you for the question. So with regards to transfusion, so that's something that happens relatively frequently in patients who have sickle cell disease and 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. So there is the risk of infectious complications, which is not very common in the U.S., but it's not 0, right? So patients can have infections. HIV infection is it possible risk, hepatitis is a risk. But then more commonly is the fact that patients can have problems like what you call iron overload because when you give red blood cells, red blood cells have hemoglobin even that has iron. And over time, that can accumulate accumulated higher levels can cause organ dysfunction as well. And so that becomes an additional burden for patients with sickle cell is. And that problem that we see with repeated transfusion in patients with sickle cell disease is that they can have this problem called red blood cell aluminization. So that means that these patients actually have antibodies that makes it more difficult for them to get subsequent blood transfusions. And so the benefits of mitapivat in patients who have hemoglobin responses that 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 and things like that. So that's very exciting to see.

Yes. Great. And Dr. Anderson, anything you'd like to add?

Yes, I'll just say I agree with everything that Ken said, I think our patients, what I've seen is a lifespan position as I see that transfusion burden starting in pediatrics, the iron buildup starting at that point and then just rising over time. So this clinically meaningful decrease in transfusions that was seen in the trial and the responders, I think it's significant to the patient population, and 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 2 visits that they don't have to come to a center. So there's a visit -- our patients typically require their blood to be tight specifically for them, on average about 48 to 72 hours prior to their transfusion because of the need to get very specific units so they don't develop alloimmunization over time. And so oftentimes, patients will come in for labs 48, 72 hours before and then they come back to the clinic for transfusion. And so I think that the transitions have a significant impact on quality of life for patients and that's on top of all the other risks associated with transfusion with iron, alloimmunization, infection and other things like that. So 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 world response from both buses. Sarah, then there was the second question from Sam about, is there any correlation between transfusions, and I think you'd asked about the pain, for example?

Yes. So 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. And I do want to stress what the 2 physicians actually just highlighted the importance of reducing transfusions just because of the risk and the impact to the patient population. And we hear that sentiment when we now present to REIGNITE trial, the Phase III confirmatory trial, to physicians to participate with their centers that there's a lot of for that trial because of all of the reasons that were just highlighted by Dr. Anderson and Dr. Ataga.

And I show our next question comes from the line of Gregory Renza from Truist Securities.

It's [indiscernible] on for Greg. Just a couple from us on the RISE UP data, the hemoglobin response was clearly rapid, separating from placebo by week 2 and holding through week 52, as you remarked on. I'm wondering how you're thinking about leveraging that onset clinically, does it lend itself to a trial of therapy or treat a target approach where you can identify nonresponders early? And then 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 you've discussed today?

Thanks, [indiscernible]. That's -- both of them are good ones for Sarah to answer.

Well, yes, indeed, you could see the data set that the hemoglobin responses were observed rapidly as Dr. has highlighted at week 2 is the first measurement we take within the trial, and that's where you start seeing the separation of the line. That being said, I hope people also have an opportunity to look at the thalassemia data in which we see that yes, we have a lot of great response early on, but some people continue to evolve their response along the way. And now in the thalassemia data, actually, the response rate was up to with prolonged exposure. So this is why it's important to continue to follow patients in the extension study to understand how -- up to how long one can expect hemoglobin response to arrive. And in regards to the baseline disease characteristics that were -- is there anything that can predict who is going to respond? Again, as Dr. highlighted in the presentation, we really looked at like prespecified a lot of factors to look at to try to determine who would response to who would not respond. And there is nothing that actually pops out that proactively can predict who is going to have a response. And that is, again, very, very consistent with what we've observed in the thalassemia and in the PKD patient population. And 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 if this actually working for the patient yes or no, and then decisions can be made by the physicians and the patients together on what is the best course of action.

And we've heard that consistently since November, actually, when we did the top line release of the rise up data, and we heard both thought leaders as well as community physicians comment on the fact that the safety and tolerability is really reinforces this try first dynamic, which is a really important opportunity. So thank you, Sarah.

And I show our next question in the queue comes from the line of Emily Bodnar from H.C. Wainwright.

Congrats on the progress as well. Maybe one on the transfusion burden data. Can you kind of help us understand the differences between the total RBC units transfused, which kind of look too different from placebo compared to the average RBC units transfused, which was clearly more significant? And then for a second question, given the confirmatory trial is lowering the age to 12 from 18, can you maybe discuss how much you would expect that to increase the addressable patient population versus RISE UP and maybe just like unmet need in adolescence

Okay. So thanks, Emily. Sarah, do you want to comment first on the transfusion aspect of I think the question is about RBC?

Emily, so when you look at the data of the RISE UP patients, we actually see positive effects for -- however, we look at the red blood cells units transfused, both meeting the frequency plus the red blood cell unit. So the totality of the data shows that it is very consistent pointing towards favoring Misapita. The other thing here is for RISE UP when you're saying the overall lot units transfused, this is not a heavily transfused patient population, right? There was -- this is not a chronically transfused patient population for stroke prevention or something like that. Just as it's occurred clinically, and that's where we did see these great results. And as mentioned also in the remarks, these results were stronger than hydroxyurea results. And so we feel very confident about where we are going with this confirmatory trial.

And then, 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. So Emily, we provided some information on the population as it's currently As a reminder, our label, the initial label, potential label will be based on the RISE UP data which is ages 16 and older. And in the U.S., there are about 75,000 patients with sickle cell disease that reflect 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 who 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 efforts. We're super excited about the opportunity through the comparator study to actually study the product and provide data in the younger age group of 12 and older. And I said that kind of gets added to the label over time, I think it's going to position us very well to move into that broader patient population and bridge the gap towards the 100,000 patients that are sickle cell disease in the U.S.

Great. Thanks, Emily.

And I show our next question comes from the line of Salveen Richter from Goldman Sachs.

This is Lydia on for Salveen. Congrats on the update. Maybe just another for the 2 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. So is this more or less reflective of the overall population?

Thanks, Lydia. So 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 received transfusions, just reinforcing the point that Sarah made, this is to match the confirmatory trial. It's really about episodic transfusions.

Correct. Yes. So 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 scheduled 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. And so they're in recurring transitions 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. And so we have a much larger group that are receiving enough transfusion scattered throughout each year that they are developing significant iron overload. And on the adult patient side, we see diminishing returns from hydroxyurea, where patients that had been doing great with higher hemoglobins, those hemoglobins are starting to decline and they are needing more frequent episodic transfusions due to symptoms. And in certain patients that are also needing erythropoietin add-back in combination with hydroxyurea in order to try to reduce transfusion burden. And so 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

And Dr. Ataga -- before we just move on, we'll have Dr. Ataga comment as well.

Yes. So thank you. So I do agree with Alan. And just to add to that. So I would say that home transfusions especially. So there are 2 ways we need to transfuse patients. So patients can get transfused episodically. And many times, it's because they have a acute complications. They come into the hospital because they are sick with it. It could be that they have a acute pain episode or some of that complication what we call acute chest syndrome. So hemoglobin level goes down and to get transfused therefore, symptoms or for treatment of the complication. Our patients can have what's called chronic transfusions. And typically, this refers to patients to get blood transitions approximately every 4 weeks-or-so, 3 to 4 weeks. And many times, it's something that's ongoing. And so for patients who get chronic transfusions for reasons like stroke prevention or because they've had an actual stroke in the past, which was secondly prevention of stroke or other reasons. I would say that the numbers in my patient population is similar to what Alan talked about in between 5% to 10% of patients get transfused. But amongst patients, we get trans episodic that's much higher. So I don't have the actual numbers in front of me, but I would say it's much higher to 30%, 40% or even 50% overhead on that. So I get transfused once a year or would there be less than that. And so having data for it draw that decreases transfusion requirements in patients with sickle cell disease is obviously very exciting to be able to help to reduce complications linked to transitions in this patients.

Very helpful. Sarah?

Yes. Thank you for both those perspectives. And I think for us, like from a clinical trial perspective, we're really just looking at the transfusions as an end point to further confirm and measure clinical benefit for the improvements we now see in the trial for the antihemolytic effect that we've seen improvement of hemolytic anemia overall, so are excited to embark on the REIGNITE trial.

And I show our next question in the queue comes from the line of Tess Romero from JPMorgan.

I think one of the KOLs touched on this earlier, but in the context of what you know today, around mitapivat 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, Tess. So maybe we'll start with Dr. Ataga, and I'll just phrase the question: it's 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. But Dr. Ataga, perhaps you could start by just commenting on what else you'd like to see?

Yes. So thanks for the question. So I would say that the data for mitapivat is quite exciting. But obviously, we can always do better, right? And so I would say tebapivat, couple of things. So for one, that drug seems to be administered once a day. And so if you have a drug that's taken once a day compared to a drug that's taken 2 times a day, most people would prefer that likelihood of missing doses is less. So I think that's an advantage to that. And then if the results of the available data confirm that tebapivat has this impact on having had hemoglobin response. So that may also be a good thing. So not only may that be high hemoglobin response efficient have higher responses in terms of hemoglobin or that might also translate into decreased complications, such as painful episodes, decrease improvements in fatigue scores in patients with sickle services. So that hemoglobin response may also translate into improved clinical benefit for patients with sickle cell disease. So we'll have to see what the data show. But I think potentially, if it does what we hope it does, tebapivat might may be more convenient in terms of administration to patients and they might have even better hemoglobin responses and decreasing complications of just pain and improvement in fatigue.

Okay. Thanks. And Dr. Anderson. And then what I'll do is have Sarah comment on, of course, what we're looking for in terms of continued development. But Dr. Anderson, maybe you could comment as well?

Sure. Yes, 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 as you near normalization of hemoglobin and you have the decrease in all of these hemolysis parameters, you see that many complications, symptoms that are occurring in patients start to go away. And so I think that the further increase in hemoglobin, I'd like to see even further normalization hemolysis markers as well as LDH. And then seeing the downstream effects of that. So hopefully, reduction in VOCs, 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. And I think you guys summarized it perfectly because now we know, of course, from the RISE UP trial that hemoglobin response once we have a global response it drives a lot of the other benefits that we can observe in the sickle cell disease patient population. So that's indeed what we are hoping for that tebapivat can deliver more globin responders or higher hemoglobin response because we do now understand based on the RISE UP data that, that is really important to drive all of the additional benefits. So we'll just -- now, as you know, we've announced that we are anticipating data for tebapivat in the second half of this year. So more to come. .

Thanks, Tess.

Thank you. And I share our last question in the queue comes from the line of Luca Issi, RBC.

Maybe just a quick one. Maybe, Sarah, you obviously filed mitapivat recall disease almost exactly a month ago to this day, I think, on May 12, so 60-day clock is obviously ticking. Have you had any informal interactions with the FDA since you filed? And maybe be bigger picture, how confident are you that the file will be accepted? And do you expect standard or priority review? So that's one. And then maybe second, Veda. On the commercial side, how are you thinking about a scenario where you get approved on accelerated based on RISE UP, but your competitor, maybe reach the market with a full approval based on reduction in crisis, do you think the docs and payers will favor your competitor or do you think that everybody would kind of look at these 2 molecules as broadly similar, given the same mechanism of action? Any thoughts there much appreciated?

Thanks, Luca. So Sarah can start just with 1 clarification, we're talking about mitapivat. And then Sarah can comment on the unmet need that exists and how we think about the commercial opportunity.

Yes. Thanks for the question. And yes, so it's our mitapivat sNDA filing that we announced about a month ago. And we, of course, continue to engage with the agency along the way because we actively filed at this point. And that's really it. So maybe I'll hand it over to you

Absolutely. And I think we turn it from the call today, and it is very consistent with what I hear interacting with physicians like-like now here at at the moment as well. The sickle cell disease with a high a very, very limited treatment option still the opportunity to have multiple products on the market is a huge advantage across the board. We don't know much about this update, 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 physician from the perspective that the hemoglobin improvement can lead to downstream benefit formation, both in terms of quality of life as well as a reduction in pain crisis, and we'll wait to see how the data continues to evolve and these things that the reduction of the can be potentially leading the future to reduction in the organ damage in these patients as well. So we feel extremely good about our profile and opportunity for us to commercialize. And don't forget this is our third potential indication in the hemolytic anemia. We have very strong system and profile. And a lot of safety clinical studies. So not only for the clinical studies, but also in the market as well. So we are getting ready for a potential launch.

Thank you. That concludes our Q&A session. I would now like to turn the conference back to Brian Goff, Agios' 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 at Agios. And 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 antihemolytic profile across both thalassemia as well as sickle cell disease. More broadly, these data highlights 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. So we leave EHA confident in our path forward, executing the AQVESME launch, advancing mitapivat 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.