Agios Pharmaceuticals Q1 2026 Earnings Call - AQVESME Launch Momentum Accelerates, sNDA Filing Set for Q2

Operator: Good day, and thank you for standing by. Welcome to the first quarter 2026 Agios financial results and business highlights. At this time, all participants are on a listen-only mode. After the speaker’s presentation, we’ll open up for questions. To ask a question during the session, you will need to press star 11 on your telephone. 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.

Morgan Sanford, Head of Investor Relations, Agios Pharmaceuticals: Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals’ first quarter 2026 financial results and business highlights. You can access the slides for today’s call by going to the investor section of our website, agios.com. Please note we’ll be making certain forward-looking statements today. Actual events and results could differ materially from those expressed or implied by any forward-looking statements because of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. On the call with me today from Agios are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; Tsveta Milanova, Chief Commercial Officer; and Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development. Following prepared remarks, we will open the call for questions.

With that, I am pleased to turn the call over to Brian Goff.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Morgan. Good morning, everyone, and thank you for joining us. Next slide, please. At the start of the year, we outlined our 2026 strategic priorities, which are designed to drive both near-term execution and long-term value creation. We are off to a strong start entering another catalyst-rich year with clear momentum across these priorities. Turning to first quarter highlights on the next slide, we delivered $20.7 million in net revenues, representing 138% growth year-over-year. The first quarter marks the U.S. commercial launch of AQVESME in thalassemia with the REMS fully operational as of the end of January, and already we have shown strong initial demand.

We continue to expect 2026 operating expenses to be approximately flat versus 2025. We ended the quarter with a strong balance sheet, including over $1 billion in cash equivalents, and marketable securities. Importantly, we’ve advanced two priorities that are key to our growth inflection. First, the U.S. commercial launch of AQVESME in thalassemia is off to a strong start, with 242 prescriptions written as of March 31st by REMS-certified physicians, building significantly on the 44 prescriptions we reported as of the end of January. This early progress reflects solid execution as the launch continues to broaden. Tsveta will provide additional details shortly. The early momentum highlights the strong work and rare disease capabilities of the Agios commercial team.

Following our pre-sNDA meeting with the FDA in the first quarter, we now plan to submit an sNDA for mitapivat in sickle cell disease in the second quarter under the U.S. Accelerated Approval pathway, marking an important step toward expanding our PK activation franchise into a significantly larger indication. I also want to underscore the caliber of our team, whose ability to respond rapidly and rigorously to FDA feedback reflects the deep regulatory and scientific expertise we’ve built at Agios. Next slide, please. Stepping back, our strategy is to build a sustainable rare disease company anchored by a foundation in rare hematology. In the near term, our focus is on executing the AQVESME U.S. commercial launch in thalassemia and advancing the mitapivat sNDA filing in sickle cell disease.

In parallel, we are preparing for important midterm catalysts, including phase II top-line data for tebapivat, our next generation, more potent PK activator in both lower-risk MDS and sickle cell disease this year. Over the longer term, we continue to advance our early-stage clinical programs and selectively evaluate expansion into other rare hematology diseases rather, to support our sustained growth. With that, please advance to the next slide, and I’ll turn the call over to Cecilia to discuss financials. Cecilia?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: Thank you, Brian. The next slide summarizes our first quarter financial results. As we have previously shared, we will report mitapivat net revenues with U.S. and ex-U.S. components. In the first quarter, we delivered $20.7 million in worldwide mitapivat net revenues, with $18.8 million from sales generated in the U.S., driven by the recent launch of AQVESME in thalassemia. Outside of the U.S., we reported $1.9 million in sales, reflecting expected quarterly fluctuations. We reported $81 million in R&D expense in the first quarter, an increase of roughly $8 million from prior year due to workforce-related expenses supporting pipeline advancement efforts as well as increased mitapivat process development expenses.

We also reported $48 million in SG&A spend, up approximately $7 million from the prior year due to an increase in activities to support the U.S. commercial launch of AQVESME in thalassemia as well as an increase in stock compensation expense. We ended the quarter with over $1 billion in cash equivalents, and marketable securities, positioning us well to remain disciplined as we invest to maximize portfolio value and build a pipeline for long-term growth. Turning to our approach to capital allocation, on the next slide, our priorities remain clear. First, we will continue to maximize the U.S. commercial launch of AQVESME in thalassemia. Second, we are managing operating expenses in a way that is aligned with our long-term value creation.

Based on our current plans and accounting for the mitapivat confirmatory clinical trial in sickle cell disease, we anticipate 2026 operating expenses to be approximately flat compared to 2025. We will continue to diversify our pipeline, leveraging both internal capabilities and external innovation as we continue to execute our 2026 priorities with a disciplined approach to long-term growth. Please advance to the next slide, and I’ll turn it over to Tsveta to cover commercial highlights and early AQVESME used thalassemia launch dynamics.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Thank you, Cecilia. Next slide, please. Our commercial performance in the first quarter reflects exceptional execution as we transitioned the focus of our field force from PK deficiency to thalassemia. In the U.S., net revenues were $18.8 million, driven by strong early AQVESME launch demand. Outside the U.S., we reported $1.9 million in net revenue, driven mainly by thalassemia utilization in the GCC. This is in line with our expectations, given early market access dynamics ahead of securing government procurement. As in prior quarters, we expect to see continued variability quarter to quarter, driven by ordering patterns, inventory dynamics, and Gross-to-Net. Please move to the next slide. I’m very encouraged by what we are seeing from the AQVESME U.S. launch so far, and I want to start by acknowledging the tremendous work of our commercial, medical, and patient support teams.

Launch execution in rare diseases is complex, and the early progress we are seeing reflects both strong preparation and the depth of rare disease commercialization expertise we have built at Agios, supported by close coordination across the organization. 242 prescriptions were written in the first quarter by REMS-certified physicians, serving as an important early indicator of strong demand. Keeping in mind, the REMS became operational in late January. Here are a few points that are worth highlighting to help frame how we’re thinking about these early signals. As we exited the first quarter, early adoption was concentrated among highly engaged patients, including transfusion-dependent and motivated non-transfusion-dependent patients. This is consistent with expected early launch dynamics. In the first quarter, time from prescription to initiation was shorter than expected.

This was due to early engagement by patients with stronger motivation to initiate treatment, physician readiness to prescribe, as well as effective REMS coordination. However, we continue to expect average initiation timelines of approximately 10-12 weeks in the coming quarters as we advance deeper into patient segments with less frequent clinical engagement. We are encouraged by the geographic breadth of early prescriber adoption, which has been driven by community-based hematologist-oncologists. What we’re seeing so far gives us confidence in our launch readiness and the quality of demand in the early days of launch. That being said, we do not view early prescription volumes as translating into a steady run rate at this early stage of launch, particularly as demand moves more towards non-transfusion-dependent patients and adoption progresses beyond the most motivated, highly engaged patients.

The next slide captures both the strong early reception of AQVESME and how we’re building towards sustainable growth. Feedback from the field has been very encouraging. Physicians and patients recognize AQVESME’s meaningful clinical profile. REMS onboarding is running smoothly, and our patient support services are helping patients initiate therapy. As we look ahead, our focus is on three things. First, expanding prescriber engagement across both academic and community settings. Second, broadening adoption into non-transfusion-dependent patients who represent most adult diagnoses. Third, advancing payer access to support timely treatment initiation. Taken together, we’re encouraged with how AQVESME is being received in these early days of launch, and we are focused on executing against the key levers that will drive durable adoption over time. I’m very proud of the team’s execution to date.

The performance in the first quarter reinforces the team’s launch readiness and deep understanding of this market.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: We believe this strong foundation positions us to deliver on both the launch of AQVESME in the U.S. as well as potential future launches as we look to expand our rare disease portfolio. Please move to the next slide. With that, I will hand the call over to Sarah to cover key R&D highlights from the quarter.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Thank you, Tsvetelina. Next slide, please. We continue to advance a robust pipeline anchored by our PK activation franchise and complemented by differentiated early-stage clinical programs. In the first quarter, we announced plans to initiate 2 pediatric mitapivat trials in thalassemia, ENERGIZE Kids T in transfusion-dependent patients and ENERGIZE Kids in non-transfusion dependent patients. We look forward to the potential to expand access to this transformative medicine into pediatric populations. We are looking ahead to upcoming second quarter readouts, including phase II-B top-line data for tebapivat, our next-generation PK activator in lower risk MDS. This study evaluates 10, 15, and 20 milligram dose levels across a broad patient population with eight consecutive weeks of transfusion independence as the primary endpoint. While this represents a higher risk opportunity, we see meaningful potential for an oral therapy in this setting. Please move to the next slide.

In the first quarter, we completed a pre-sNDA meeting with the FDA and aligned on a path towards U.S. Accelerated Approval for mitapivat in sickle cell disease. Since that meeting, we’ve had a series of informal and formal engagements to gain official alignment on the confirmatory clinical trial required under this pathway. We are pleased with the progression of these discussions and now expect we will file an sNDA in the second quarter. We look forward to sharing additional data from the RISE UP phase III trial at an upcoming medical congress, including analyses that informed our selection of the confirmatory clinical trial’s primary endpoint.

Taking a step back, as we consider development of the confirmatory trial design, we emphasized operational feasibility, including enrollment timelines and time to completion while looking to maximize probability of success and the potential to further enhance the mitapivat label should U.S. full approval be granted upon results of confirmatory trial. Next slide, please. In parallel, we are advancing tebapivat, our next-generation PK activator in phase II studies across low-risk MDS and sickle cell disease. Tebapivat was intentionally designed to go beyond first generation PK activators. It is structurally differentiated with potent dual activation of PKR and PKM2 and PK and PD properties that support once daily dosing without the need for a taper. Importantly, the early clinical data reflect these design features. In sickle cell disease, tebapivat demonstrated a long half-life of approximately 87-93 hours.

Those dependent reductions in 2,3-DPG and increases in ATP and pharmacodynamic effects that remain durable for up to 4 weeks after the last dose. We also observed a mean hemoglobin increase of 1.9 grams per deciliter at the 5 milligram once daily dose. Beyond red blood cell metabolism, tebapivat shows broader biological activity driven by PKM2 activation. In preclinical models, this translated into anti-fibrotic effects, including reduced glomerular injury and myofibroblast signaling, supporting the potential for disease-relevant activity beyond mature red blood cells. In low-risk MDS, we observed early clinical signals, including transfusion independence in the low transfusion burden cohort. However, we observed 50% lower drug exposure relative to healthy volunteers, which prompted investigation at higher doses.

The ongoing phase II-B study, which is evaluating higher doses in a broader lower risk MDS population, will test the hypothesis that deeper PKR and PKM2 activation may extend biological activity into erythroid maturation in the bone marrow. In sickle cell disease, our phase II study is designed to rapidly assess hemoglobin response and key markers of hemolysis to confirm whether this deeper biology translates into broader clinical benefit. We look forward to reporting top-line phase II-B data in lower risk MDS in the first half of this year, followed by top-line phase II data in sickle cell disease in the second half of 2026. Please move to the next slide, and I will hand the call back to Brian for closing remarks.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you, Sarah. Next slide, please. As you’ve heard today, 2026 is shaping up to be a growth inflection and catalyst-rich year for Agios, with meaningful progress across our commercial business and our pipeline. In the first half of the year, we advanced the regulatory path for mitapivat in sickle cell disease. We expect phase II-B top-line data for tebapivat in lower risk MDS, along with phase I healthy volunteer top-line data for AG-236. In the second half of the year, we anticipate phase II top-line data for tebapivat in sickle cell disease, as well as phase I-B proof of mechanism data for AG-181 in phenylketonuria. Throughout the year, we remain focused on executing the U.S. commercial launch of AQVESME in thalassemia with the goal of building a strong and sustainable commercial foundation. Next slide, please.

Stepping back, we believe Agios is differentiated by the combination of a growing commercial base and a pipeline increasingly weighted towards later-stage high-value opportunities. As shown here, our current pipeline represents greater than $10 billion in potential market opportunity in 2030. Most importantly, everything you’ve heard today is grounded in our commitment to the patients we serve, patients living with serious and often underserved rare diseases who are still waiting for better treatment options. I also want to recognize and thank our employees. Their focus, expertise, and dedication are what make this progress possible. From advancing critical clinical and regulatory milestones to executing a complex commercial launch with care and discipline. With that, we appreciate your continued interest in Agios, and I’d now like to open the call for questions. Operator, please open the line.

Operator: Thank you. As a reminder, to ask a question, you will need to press star 11 on your telephone and wait for a name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the connect roster. One moment for our first question. Our first question will come from line of Samantha Simunovic from Citi. Your line is open.

Samantha Simunovic, Analyst, Citi: Hi. Good morning. Thanks very much for taking the question, and congratulations on the early launch progress for AQVESME. Just sticking with that theme, first question then is just a little bit about the demand of AQVESME you’re seeing thus far in the second quarter. I’m wondering if there was a bit of a bonus component in the first quarter from those highly motivated patients. As you look into the second quarter prescription performance, are you seeing similar cadence in those prescriptions coming in, as well as an increase in REMS-certified healthcare professionals? Thanks very much, and I have a follow-up.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Sure. Thanks, Sam. I’m gonna let Tsveta comment, and of course, we’re gonna stick to the first quarter dynamics. There’s obviously, you know, good momentum that we were proud to report today. Tsveta, you wanna take over?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Absolutely. As I said, we are very excited with the early launch and the progress we’ve made. We said we had 242 prescriptions from REMS-certified physicians as of March 31st. The early uptake is really driven by these highly engaged and motivated patients, which included both the transfusion-dependent patients and the motivated non-transfusion dependent patients. I wouldn’t take Q1 to be the run rate for upcoming quarters, but what I can tell you is that we still expect very strong demand and uptake as the team continues to execute very strongly. The reception from both patients and physicians on the AQVESME profile has been very, very positive.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Sam, you had a follow?

Samantha Simunovic, Analyst, Citi: I did, yes. Thank you for that answer. That was helpful. A couple follow-ups on tebapivat. Just first on the timing of the MDS data, I’m wondering if there’s any additional clarity you could share there and when that data will come this quarter. Just secondly, on sickle cell disease, I’m wondering how you’re thinking about the market opportunity for mitapivat, given some recent competitor data. Just how do you think about developing mitapivat? Obviously, you’re moving towards Accelerated Approval filing, but you have tebapivat in the second half that could have potential best-in-class efficacy based on those early data signals you walked through in the prepared remarks. Just how are you thinking about that market developing as we go forward? Thanks very much.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: We’ll go in sequence. Sarah can comment on tebapivat for MDS, and basically, we’ve given the timing that we’re expecting.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Exactly. Sam, the timing that we’ve highlighted is the first half of this year. That is, that is what we’re sticking to. For sickle cell disease, the timing is the second half of the year. The teams are making great progress towards those deliverables.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: I’ll turn it back to Sveta to comment on. We’re clearly, Sam, in a position of strength having mitapivat and all the progress that we talked about this morning for our accelerated pathway for sickle cell disease, and then the benefit of having tebapivat, a next generation, more potent PK activator that we’re looking forward to phase II data. Sveta perhaps can talk about the overall franchise goal that we have.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yeah, absolutely. We see a very significant commercial opportunity in sickle cell disease, including both Mitapivat and tebapivat. When we think about Mitapivat, we see sickle cell disease as a disease that can support multiple treatment options, and we will be looking to maximize the commercial opportunity, assuming that we have a label. That’s driven by the fact that we’ve seen a very strong response and positive response from the caregiver community on the strength of our hemoglobin responder data. They are communicating about the need of anti-hemolytic agent, especially an agent that can, with hemoglobin responders, can demonstrate a potential benefit in other meaningful endpoints such as quality of life, and potential reduction in pain crisis.

We haven’t seen the HIBISCUS data yet to be able to comment more on, but we’re starting from a position of strength when you think that this is our third indication on the market. There is a strong familiarity of that community with the product. We have over 1,000 patient years of data and a strong market experience. We will see that as a good anchor for our franchise building.

When it comes for tebapivat, of course, we’ll need to see the phase II data. We’ll need to see how the competitive environment moves forward. We’ll be looking to have a best-in-class positioning with that product, and we’ll provide more information as we get the data.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Alex Shanahan from Bank of America. Your line is open.

Alex Shanahan, Analyst, Bank of America: Hey, guys. Thanks for taking my questions, and congrats on all the early launch progress this quarter. Two questions from me, one on sickle cell and one on the launch in Thal. I guess, first on Thal, in patients transitioning from clinical study to commercial drug, is covering costs of therapy part of ensuring continuity of treatment? Just trying to think through how many of the 242 scripts were patients moving from the clinical trial and how they might translate to revenue this quarter and going forward.

On the sNDA for sickle, curious when you expect to get feedback from the regulator on the proposed design of the confirmatory study, and whether that’s an update you’ll share or if the next we’ll hear on the program is just that the sNDA has been submitted. Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah, we’ll take them in sequence. Starting with thalassemia, maybe just comment on the Open-Label Extension and studies.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Right. Exactly. Alex, patients are in open label extensions on the Thal clinical program, those are still ongoing and, of course, help us to continue to highlight the maintenance of effect in this patient population. In addition, the proportion of U.S. patients in those studies is small because it’s a big global study. In regards to sickle cell disease, we are, you know, very pleased with the progression of the engagements we’ve had and the pace of the engagements we’ve had with the FDA, which of course, allowed us to further fine-tune the timeline for submission. We’ve updated to state that we would file in Q2. More details on the clinical trial we will highlight before it goes as clinicaltrials.gov.

Of course, we’ve stated that we will also present data at or around EHA, and that data did inform us in this trial. I do wanna take a step back here and just highlight that as I stated in my prepared remarks that the trial, of course, is also designed in such a way that we prioritize operational feasibility and probability of success here. That is going to be our focus with this.

Alex Shanahan, Analyst, Bank of America: Okay. Maybe I could just follow up just on the continuity of treatment piece. I guess of the 242 scripts, I guess how many of those were booked as revenues in the quarter? I guess how do you see that evolving sort of as payer access comes online over the coming quarters?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Cecilia, do you want to comment on the metrics or?

Cecilia Jones, Chief Financial Officer, Agios Pharmaceuticals: As we stated, we split U.S. and ex-U.S. It’s of the U.S. revenues. The way to think about it is, you know, we guided PKD to be about $45 million-$50 million for the year, and the quarter has been in line with that, with the rest coming in from thalassemia. There is a lag on the prescriptions to when patients get on therapy, and that’s what Sarah was saying. Like, we’ve seen it be a little faster than what we thought, which we think it’s going to eventually be in that 10-12 week range.

Alex Shanahan, Analyst, Bank of America: Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks a lot.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Emily Bodnar from H.C. Wainwright. Your line is open.

Emily Bodnar, Analyst, H.C. Wainwright: Hi, good morning. Thanks for taking the question. First one, with your conversations with the FDA about the sNDA for sickle cell disease, are you also expecting a REMS for sickle cell disease or is that only for thalassemia? Follow-up question, with the phase II sickle cell data for tebapivat expected later this year, could you maybe give us some expectations about, you know, what you’d like to see relative to phase II data from mitapivat and tebapivat, to kinda get confident in that best-in-class profile? Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Sarah, we’ll start with.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Yeah

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: continued encouraging interactions with the FDA and the question on REMS.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Yes, of course. As you know, we now have optionality because we have Endari and AQVESME. Both of these are options, each having, you know, different pros and cons. Either way, our teams would be able to execute on any of those options. As it relates to the phase II data, it’s a dose-finding study. Of course, we’re looking for a dose in phase II to bring forward. We’re also looking for depth and breadth of hemoglobin response.

Operator: Thank you. One moment for our next question. Our next question will come from the line of Eric Schmidt from Cantor. Your line is open.

Eric Schmidt, Analyst, Cantor: Good morning, congrats on a terrific launch. Maybe on this 242 prescription number in the first quarter, that’s obviously an enormous number. I think, Tsveta Milanova, you told us back in February that through January 31st, you had 44 prescriptions. It looks like there’s been a pretty meaningful acceleration in February and March. Maybe you could just confirm whether my math there is correct and maybe square the circle relative to the comments you made about, you know, not extrapolating forward the current run rate, ’cause if anything, it seems like you’re on an accelerating pattern. Thank you very much.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yes, we are very excited about the progress, Eric. The 242 prescriptions from REMS-certified physicians of January 31st reflect the totality of the first quarter. As a reminder, we started actually actively promoting the drug as we got label. The demand was generated throughout the whole quarter. The REMS became operational end of January, the demand was generated throughout January as well. I’ll look at the quarter as a totality. That’s what I mentioned, I wouldn’t take these two numbers and kind of extrapolate from there in the future quarter and wouldn’t take that run rate.

We are still expecting to see a strong demand moving forward as the team is executing and the patients and physicians are very positive on the profile and looking to engage further.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Eric, maybe I’ll just take this opportunity to reinforce, adding to your comments that what’s so special about the AQVESME launch is we have three key ingredients. First is AQVESME addresses a significant unmet need with thalassemia. Secondly, the community, i.e., physicians as well as patients, are already reflecting enthusiasm for the profile. As you just said, you know, third, Tsveta and the Agios team are very well prepared, and they know how to execute, and we’re very proud of their early progress.

Eric Schmidt, Analyst, Cantor: Terrific progress indeed. Do we have a sense of what % of the initial REMS prescribing patients are likely to convert or what the conversion ratio is?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: The, in the, in the initial quarter, as I mentioned, we really kind of captured some of the most motivated and engaged patients, and our conversion from prescription to treatment initiation was actually faster than expected. As the quarter is progressed over time, we still expect the initiations to be 10-12 weeks. Always we’ll try to shorten it. The primary driver for that is that we’ll be moving into patient segments that have less frequent interactions with the healthcare system as we go deeper into the NTDT segment as we, as we’ve spoken in the past.

Eric Schmidt, Analyst, Cantor: Maybe asking a different way, have you lost any of the 242 patients that you now no longer think are likely to convert?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: So far, I think we could characterize, Eric, that the REMS has been well embraced by both the physician community as well as Tsveta says, the motivated patients. We’ve had, you know, we feel very confident with the high conversion, I’ll call it, of those early patients that have started on or were prescribed AQVESME and then converted onto therapy.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yeah. Sorry, Eric, maybe I didn’t get your exact question. The REMS is not a hurdle to treatment initiation at all. What we see in terms of a conversion rate and, you know, it is very typical for rare disease launches. We’re not out of the extraordinary because of the REMS.

Eric Schmidt, Analyst, Cantor: Great. Congrats and thanks again for taking my questions.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks a lot.

Operator: Thank you. Our next question will come from the line of Marc Frahm from TD Cowen. Your line is open.

Marc Frahm, Analyst, TD Cowen: Hey, thanks for taking my questions and congrats on all the progress with AQVESME. Maybe just following up on some of the answers there to Eric’s questions. It sounds like at least some of these, you know, the extra kind of 200 prescriptions that you’re kind of talking about now versus the end of January, I guess maybe were even written before January. Is that right? They just weren’t by a REMS-certified physician and kind of what’s changed is the REMS certification status. Is that the right way to kind of square the commentary? You know, some of this kind of caution around that trajectory of TRx maybe slowing or the fill time pushing out a little bit. Have you actually seen that yet or you’re just cautious that that may happen as we move into future quarters?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Marc. Maybe what will help here is Tsveta Milanova can just, like, take a step back to the launch timing and what occurred in the first quarter. ’Cause there was a initiation of demand and then there was the operationalization of the REMS. Do you just wanna talk through that and then reflect on the source of the 242 prescriptions?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yeah, absolutely. The 242 prescriptions are re-reflective of all of the work that we’ve done in excellent launch preparation. We had a lot of clarity of where likely the prescriptions are gonna come first, and we initiated these interactions and promotional activities as soon as we got the label. They’re a reflection of the work that we’ve done for the whole quarter. In the first month, we didn’t have the REMS operational, and the team still did an excellent job to get prescriptions from REMS-certified physicians in that phase of the launch. And we’ll continue on that journey once the REMS was operational. Obviously, more physicians who are waiting for that operational date to start prescribing, they did start prescribing.

We are very pleased with what we are seeing right now because the prescriptions are coming from a very healthy geographic breadth. They’re coming from the community prescribers, majority where the majority of the patients are managed right now. We see these kind of highly motivated and engaged patients starting therapy, which is fantastic for us because we know that the thalassemia community is actually very well connected, and that early launch experience with the patients will actually support the kind of the positive feedback and the profile of the product as well.

What I can tell you is that moving forward, I wouldn’t take the two data points in Q1 and extrapolate from there, but I’m very confident that we’ll have a strong uptake and penetration moving forward, as we continue to the launch, typical with non-life-threatening rare disease conditions.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Marc, on the second part of your question about the 10 to 12 weeks, that Tsveta commented on in her prepared comments, we have been encouraged that these motivated patients have translated to therapy faster than that in some cases. Again, this is relative to the motivation of both the physician and the patient. The reason to guide on average, that’s an expectation going forward, is as we penetrate further into the non-transfusion-dependent patient population, we expect there will be, you know, perhaps a mitigating factor on the enthusiasm aspect, and it might take a little bit longer for those patients to convert to therapy.

Marc Frahm, Analyst, TD Cowen: Okay. Completely understand that. Maybe just to push on it a little bit. You know, presumably also as you get further into the launch, you also have a dynamic of more payers kind of having regular processes and things that tends to kind of shorten the timelines within a given payer.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yeah.

Marc Frahm, Analyst, TD Cowen: I guess it sounds like you expect it to be more than counteracted by the kind of difference in enthusiasm from the patient itself.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Yeah. Definitely the team is doing an excellent job right now, and we haven’t had any payer hurdle so far. Of course, we’ll continue to look for ways to shorten the time from prescriptions to treatment initiation. We’ll look to advance. It takes about 6 months on average to get the payer policies in place. As of now, similar to patients and physicians, payers have been very receptive of the profile and market access has not been a hurdle.

Marc Frahm, Analyst, TD Cowen: Okay. Thanks a lot and congrats on all the progress.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Marc.

Operator: Thank you. Our next question will come from the line of Salveen Richter from Goldman Sachs. Your line is open.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals2: Hi, this is Lydia on for Salveen Richter. Thanks so much for taking our questions and congrats on the launch updates here. Maybe just another question on the launch. Could you maybe just speak to the treating physicians and treatment settings that you’re seeing here? Are you still seeing a majority of prescriptions coming from the community hem-oncs? Is the team starting to engage with physicians beyond those who were targeted ahead of the launch? Thanks so much.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Absolutely. We see a very healthy start of the launch when we think from a prescriber base. We’ve seen prescriptions coming both from the academic and community setting, but the majority of the prescriptions are coming from the community setting, which is exactly as we expected it. That’s driven by the fact that patients with thalassemia are actually managed mainly in the community setting. We see prescriptions coming from across the country, which is fantastic. As we move forward, the patients will continue to increase the breadth of prescribing. Of course, we’ll focus on depth as well, but the majority of the business is gonna continue to grow breadth.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals2: Thanks so much.

Operator: Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you.

Operator: Our next question will come from the line of Tessa Romero from JPMorgan. Your line is open.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals0: Hey, guys. Thanks so much for taking our questions this morning. You know, I just wanted to double-click back here to one of the initial questions on the call here. You know, ultimately, what do you see as the implications of Novo’s recent results, the next steps at Agios, and how does this change your view of what you need to see to drive tebapivat forward in sickle cell disease as well?

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Right.

Thanks, Tess. Maybe Sarah can start with our focus.

Yep

-on, mitapivat, and then we can comment on tebapivat as well.

Sure. Hi, Tessa. We haven’t seen the full Hibiscus results yet. As Tsveta Milanova highlighted, I mean, we see a clear commercial opportunity in sickle cell disease with mitapivat. As she highlighted as well, there is room for multiple players given the prevalence and the, you know, the disastrous nature of this disease. Of course, we’ll look to maximize commercial opportunity with mitapivat. That is possible with our data set in Rise Up. We have, again, a very strong anti-hemolytic profile in our data set. The strength of the hemoglobin responders data is definitely there because as we’ve highlighted, we have seen impact on VOCs, but sickle cell disease is more than VOCs. We’ve seen impact on hospitalizations, fatigue, quality of life.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: There is really a lot of excitement for our drug in the community, both by patients and physicians. Of course, we are also as we highlighted in our prepared remarks, very pleased with the progression of the engagements we’ve had with the FDA so that we’re now able to update our expected filing to into Q2. We are very pleased with where we are.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals0: Okay, great. Sarah, if I can just follow up quickly on that point. You know, is there anything that you would like to better understand in the fuller HIBISCUS dataset when we do see it?

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Well, yes. Obviously, like, the data is, you know, very limited right now that we have to our availability. Anything as it relates to standard study metrics, I would love to see.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals0: Okay. Thank you.

Operator: Thank you.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thanks, Tessa.

Operator: Our last question will come from the line of Greg Renza with Truist. Your line is open.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals3: Hi, team. This is support on to Greg. Congrats. May I add a congrats to the launch, Tsveta Milanova. One question on AQVESME. With the momentum continuing to build, you know, you have 242 prescription in first quarter, are you starting to see any early signals of patient persistence? You know, patients staying on therapy, you know, given that this is a chronic setting. Any differences in the patterns between transfusion-dependent versus non-transfusion dependent? I have a follow-up.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Absolutely. As we said, we are very early in the launch, and there is a time lag between a prescription and treatment initiation, and then the patients need to go through a month of therapy to start seeing more of the continuation rate. You know, we’ve seen PYRUKYND in PK deficiency performing extremely well in the real world. We expect to see the same strong performance in thalassemia as well. You know, sometimes we talk about the ramps as kind of, you know, paperwork and work, but actually it helps with the frequent interactions between patients and physicians and actually can support continuation of therapy as well. We’ll wait and see. That’s one very important factor we’ll continue to monitor.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals3: Got it. Thanks, Tsveta. A second question on mitapivat in sickle cell disease. Assuming Accelerated Approval, how do you think about the opportunity for early uptake based on hemoglobin as a surrogate endpoint on potentially on the label, while additional outcomes data are being generated, you know, in a confirmatory study, and especially in light of etavopivat hitting the VOC endpoint?

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah. This is a little bit reflective of what Sarah had commented on as well, that sickle cell disease has very high unmet need. As Sarah said, it’s a multidimensional disease. There are many things to address clinically within sickle cell disease. We stand proud and tall with the RISE UP data that we’ve seen, particularly as well the responder analysis. Tsveta and her team are, of course, already preparing commercially for that potential opportunity ahead with the Accelerated Approval pathway.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals1: Just, if I may add, the data from RISE UP that we’ve highlighted to physicians and to patient communities has been very well received.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Yeah.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals3: And if I may, thanks so much, Brian and Sarah. Could you maybe expand a little bit on the confirmatory study? What are you thinking in terms of the confirmatory endpoints, and how might that compare to, you know, the potential VOC data that we might see in Hibiscus? You know, just when it comes to treatment selection.

Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development, Agios Pharmaceuticals: Yes. Thanks. The endpoint, as highlighted, is informed by the RISE UP data set, in which we’ve collected data systematically, prospectively. We’ve had also great engagements with the FDA, and that has progressed very nicely. Again, we are now able to speak, though, our intent to file in the second quarter. We’ve also highlighted before that we will be presenting data at or around EHA around all of the data, so including the data that informs this confirmatory trial, and that we will also share more ahead of our posting on clinicaltrials.gov.

The last thing I wanted to stress, and this is really important, this is a confirmatory trial, so we really have prioritized the operational feasibility as well with probability of success to be able to deliver meaningful data that then, of course, would allow us, at that time, to hopefully be able to put that data into label at the time of full approval when the results allow. We are very excited about where we currently are. We have really, you know, great confidence in our data and the path that we are on.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals3: Got it. Thanks and congrats again.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Thank you.

Operator: Thank you. This concludes the question and answer session. I would now like to turn it back over to Brian Goff for any closing remarks.

Brian Goff, Chief Executive Officer, Agios Pharmaceuticals: Well, thanks a lot, Victor. Thanks everyone for joining. The first quarter clearly reflected solid execution across our strategic priorities, from the early progress with the U.S. commercial launch of AQVESME and thalassemia, as we’ve discussed, to continued advancement toward mitapivat sNDA filing in sickle cell disease, and to maintaining a disciplined financial approach. With multiple meaningful catalysts ahead this year, we believe Agios is well-positioned as we move through 2026, and we look forward to continuing to update you on our progress, including at our planned investor event during the 2026 EHA Congress. Thank you very much, everyone.

Operator: Thank you for your participation in today’s conference. This does conclude the program. You may now disconnect. Everyone, have a great day.