Agios Pharmaceuticals (NASDAQ:AGIO) Q1 2026 Earnings Call

0:00 Joining us to discuss Agios Pharmaceuticals' first quarter twenty twenty six financial results and business highlights. You can access the slides for today's call by going to the Investors 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 AGIO are Brian Goff, Chief Executive Officer Cecilia Jones, Chief Financial Officer Sveta Milanova, Chief Commercial Officer and Doctor. Sarah Huynh, Chief Medical Officer and Head of Research and Development.

0:49 Following prepared remarks, we will open the call for questions. With that, I am pleased to turn the call over to Brian. 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 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 $20,700,000 in net revenues, representing 138% growth year over year. The first quarter marks The U. S. Commercial launch of ACBESMY in thalassemia with the REMS fully operational as of the end of January.

1:39 And already, we have shown strong initial demand. We continue to expect 2026 operating expenses to be approximately flat versus 2025. And we ended the quarter with a strong balance sheet, including over $1,000,000,000 in cash, cash equivalents and marketable securities. Importantly, we've advanced two priorities that are key to our growth inflection. First, The US commercial launch of ACBESMI in thalassemia is off to a strong start, with two forty two prescriptions written as of March 31 by REMS certified physicians, building significantly on the 44 prescriptions we reported as of the end of January.

2:26 This early progress reflects solid execution as the launch continues to broaden. Sveta will provide additional details shortly, but the early momentum highlights the strong work and rare disease capabilities of the AGIO's commercial team. Second, 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.

3:20 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 ACBESMI US 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 tebipivat, our next generation, more potent PK activator in both lower risk MDS and sickle cell disease this year. And over the longer term, we continue to advance our early stage clinical programs and selectively evaluate expansion into other rare disease rheumatology rare hematology diseases, rather, to support our sustained growth.

4:16 With that, please advance to the next slide, and I'll turn the call over to Cecilia to discuss financials. Cecilia? 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 $20,700,000 in worldwide mitapivat net revenues, with $18,800,000 from sales generated in The U. S, driven by the recent launch of Agvesmi in thalassemia. Outside of The U. S, we reported 1,900,000 in sales, reflecting expected quarterly fluctuations. We reported $81,000,000 in R and D expense in the first quarter, an increase of roughly $8,000,000 from prior year due to workforce related expenses supporting pipeline advancement efforts as well as increased mitapivat process development expenses.

5:14 We also reported $48,000,000 in SG and A spend, up approximately $7,000,000 from the prior year due to an increase in activities to support The U. S. Commercial launch of ADVESTMA in thalassemia as well as an increase in stock compensation expense. We ended the quarter with over $1,000,000,000 in cash, 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 Agvezmi in thalassemia. Second, we are managing operating expenses in a way that is aligned with our long term value creation.

6:02 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. Finally, 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 Sveta to cover commercial highlights and early AgVestMe use thalassemia launch dynamics. 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.

6:53 In The U. S, net revenues were $18,800,000 driven by strong early ACVESMI launch demand. Outside The U. S, we reported $1,900,000 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 Quesmi U. S. Launch so far, and I want to start by acknowledging the tremendous work of our commercial, medical, and patient support teams.

7:50 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. Two forty two prescriptions were written in the first quarter by REMS certified physicians, serving as an important early indicator of strong demand, keeping in mind that 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.

8:35 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 ten to twelve weeks in the coming quarters as we advance deeper into patient segments with less frequent clinical engagement.

9:29 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 ACPESMI and how we're building towards sustainable growth.

10:21 Feedback from the field has been very encouraging. Physicians and patients recognize ACPESMI'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 diagnosis. And third, advancing payer access to support timely treatment initiation.

11:07 Taken together, we are encouraged with how Agfesmi 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. We believe this strong foundation positions us to deliver on both the launch of ECLESMRI 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. And with that, I will hand the call over to Sarah to cover key R and D highlights from the quarter.

12:00 Thank you, Sveta. 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 two pediatric Mestapivat trials in thalassemia, ENERGIZE KITS T in transfusion dependent patients and ENERGIZE KITS in non transfusion dependent patients. We look forward to the potential to expand access to this transformative medicine into pediatric populations. Finally, we are looking ahead to upcoming second quarter readouts, including Phase 2b top line data for debapivat, our next generation PK activator in low risk MDS.

12:45 This study evaluates ten, fifteen, and twenty 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 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.

13:33 We look forward to sharing additional data from the Rise Up Phase three 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 debapivat, 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.

14:23 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 eighty seven to ninety three hours, dose dependent reductions in 23 DPG and increases in ACP, and pharmacodynamic effects that remain durable for up to four weeks after the last dose. We also observed a mean hemoglobin increase of 1.9 grams per deciliter at the five milligram once daily dose. Beyond red blood cell metabolism, sebapivat shows broader biological activity driven by PKM2 activation.

15:12 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 fifty percent lower drug exposure relative to healthy volunteers, which prompted investigation at higher doses. The ongoing Phase 2b study, is evaluating higher doses in a broader lower risk MDS population will test the hypothesis that deeper PPR and PPM2 activation may extend biological activity into erythroid maturation in the bone marrow.

15:58 In sickle cell disease our Phase two 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 to reporting top line Phase 2b data in low risk MDS in the first half of this year, followed by top line Phase two data in sickle cell disease in the second half of twenty twenty six. With that, please move to the next slide, and I will hand the call back to Brian for closing remarks. 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.

16:44 In the first half of the year, we advanced the regulatory path for mitapivat in sickle cell disease, and we expect Phase IIb top line data for tebipivat in low risk MDS, along with Phase I healthy volunteer top line data for AG-two thirty six. In the second half of the year, we anticipate Phase II top line data for tevapivat in sickle cell disease, as well as Phase Ib proof of mechanism data for AG-one hundred eighty one in fetal ketonuria. And throughout the year, we remain focused on executing The U. S. Commercial launch of ACBESMY 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.

17:43 As shown here, our current pipeline represents greater than $10,000,000,000 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.

18:33 Thank you. Our first question will come from the line of Samantha Simenkow from Citi. Your line is open. Hi, good morning. Thanks very much for taking the question and congratulations on the early launch progress for Agios Pharmaceuticals. And just sticking with that theme, first question then is just a little bit about the demand of Agios Pharmaceuticals you're seeing thus far in the second quarter. I'm wondering if there's a bit of a bolus component in the first quarter from those highly motivated patients.

19:21 But as you look into the second quarter prescription performance, are you seeing a 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. Sure. Thanks, Sam. I'm going to let Sveta comment, and of course, we're going to stick to the first quarter dynamics. But there's obviously good momentum that we were proud to report today. So, Sta, you want to take over? Absolutely. So, as I said, we are very excited with the early launch and the progress we've made. We said we had two forty two prescriptions from REMS certified physicians as of March 31. The early uptake is really driven by these highly engaged and motivated patients, which included both of the transfusion dependent patients and the motivated non transfusion dependent patients.

20:17 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 and the reception from both patients and physicians on the Afesme profile has been very, very positive. And Sam, you had a I did. Yes. Thank you for that answer. That was helpful. A couple of follow ups on tebipivat. 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? And then just secondly on sickle cell disease, I'm wondering how you're thinking about the market opportunity for mitapivat given some recent competitor data. And then just how do you think about developing mitapivat?

21:06 Obviously, you're moving towards accelerated approval filing, but you have tebipivat 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. So we'll go in sequence. Sarah can comment on tebipivat for MDS, and basically we've given the timing that we're expecting. Exactly. So, Sam, the timing that we've highlighted is the first half of this year, and so that is what we're sticking to. And then for sickle cell disease the timing is the second half of the year. So, the teams are making great progress towards those deliverables. And then I'll turn it back to Sveta to comment on. We're clearly Sam in a position of strength having minipivat and all the progress that we talked about this morning for our accelerated pathway for sickle cell disease, and then the benefit of having tebipivat, a next generation more potent PK activator that we're looking forward to Phase II data.

22:15 But Sveta perhaps can talk about the overall franchise goal that we have. Yes, 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. And that's driven by the fact that we've seen a very strong response and positive response from the KOL 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 the potential benefits in other meaningful endpoints such as quality of life and potential reduction in pain crisis.

23:17 So, haven't seen the hibiscus data yet to be able to comment more on, but we're starting from a position of trend 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 one thousand patient years of data and a strong market experience and we will see that as a good anchor for our franchise building. When it comes for tebapivant, of course, we'll need to see the face to date, we'll need to see how the competitive environment moves forward, but 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. Thank you. One moment for our next question.

24:08 Our next question will come from the line of Alex Schranihan from Bank of America. Your line is open. 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 two forty two scripts were patients moving from the clinical trial and how they might translate to revenue this quarter and going forward. And then 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 tool here on the program is just that the sNDA has been submitted. Thank you.

25:06 Yeah, and I think Sarah can we'll take them in sequence, starting with thalassemia, maybe just comment on the open label extension and the Exactly. So, Alex, so patients are in open label extensions on the tau clinical program. So those are still ongoing and of course help us to continue to highlight the maintenance of effect in this patient population. And 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 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. So, we've updated the state that we would file in Q2.

25:57 More details on the clinical trial we will highlight before it goes on clinicaltrials.gov. And then 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 want to 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. And so, that is going to be our focus with this. Okay. Maybe I could just follow-up just on the continuity of treatment piece. I guess of the two forty two scripts, I guess how many of those were booked as revenues in the quarter?

26:53 And I guess how do you see that evolving sort of as payer access comes online over the coming quarters? Cecilia, do you want to comment on the metrics? Yes. So as we stated, we split U. S. And ex U. S. Revenues. Of The U. S. Revenues, the way to think about it is we guided PKD to be about 45,000,000 to $50,000,000 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. We've seen it be a little faster than what we thought, but we think it's going to eventually be in that ten to twelve week range. Thank you. Thanks a lot. Thank you. One moment for our next question.

27:42 Our next question comes from the line of Emily Bodnar from H. C. Wainwright. Your line is open. Hi, good morning. Thanks for taking the questions. 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? And then follow-up question, with the Phase II sickle cell data for Temepinostat expected later this year, can you maybe give us some expectations about what you'd like to see relative to Phase two data from mitapivat and atomopivat to kind of get confident in that best in class profile? Thank you. So Sarah, we'll start with continued encouraging interactions with the FDA and the question on REMS. Yes, of course. And as you know, we now have optionality because we have Enparakind and Agvesme.

28:42 Both of these are options each having, different pros and cons. Either way our teams would be able to execute on any of those options. And as it relates to the Phase II data, it's a dose finding study. So, of course we're looking for adults in Phase II to bring forward. We're also looking for depth and breadth of hemoglobin response. 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. Good morning and congrats on a terrific launch. Maybe on this two forty two prescription number in the first quarter, that's obviously an enormous number.

29:33 I think, Stadia, you told us back in February that through January 31, had 44 prescriptions. So 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 not extrapolating forward the current run rate, because if anything, it seems like you're on an accelerating pattern. Thank you very much. Yes, are very excited about the progress, Eric. And the two forty two prescriptions from REMS certified physicians of January 31 reflect the totality of the first quarter. As a reminder, we started actually actively promoting the drug as we got label. So the demand was generated throughout the whole quarter. The ramps became operational end of January, but the demand was generated throughout January as well. So I'll look at the quarter as a totality.

30:38 And 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. But we're still expecting to see a strong demand moving forward as the team is executing and patients and physicians are very positive on the profile and looking to engage further. And Eric, maybe I'll just take this opportunity to reinforce adding to your comments that what's so special about the ACPFASB launch is we have three key ingredients. First is ACPFASB addresses a significant unmet need with thalassemia. Secondly, the community, I. E. Physicians as well as patients are already reflecting enthusiasm for the profile. And as you just said, you know, Steta and the Agios team are very well prepared and they know how to execute, we're very proud of their early progress.

31:38 Terrific progress indeed. Do we have a sense of what percent of the initial REMS prescribing patients are likely to convert or what the conversion ratio is? So, 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 ten to twelve weeks always. We'll try to shorten it, but 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 entity segment as we've spoken in the past.

32:30 Maybe asking a different way, have you lost any of the two forty two patients that you now no longer think are likely to convert? So far, I think we could characterize, Eric, that the REMS has been well embraced by both the physician community as well as, far as the motivated patients. And 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 ECBSB and then converted on to therapy. Yeah, sorry, Eric, maybe I didn't get exactly your question, but we don't see any the REMS is not a hurdle to treatment initiation at all. What we see in terms of a conversion rate and it's very typical for rare disease launches. So, we're not out of the extraordinary because of the REMS.

33:31 Great. Congrats and thanks again for taking my questions. Thanks a lot. Thank you. And our next question will come from the line of Mark Frome from TD Cowen. Your line is open. Thanks for taking my questions and congrats on all the progress with ekvezmi. Maybe just following up on some of the answers there to Eric's questions. Just it sounds like at least some of these, 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 square the commentary? Then 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?

34:31 So thanks, Mark. Maybe what will help here is, so that I can just take a step back to the launch timing and what occurred in the first quarter, because there was a initiation of demand and then there was the operationalization of the REMS. Do you just want to talk through that and then reflect on the source of the two forty two prescriptions? Yeah, absolutely. So the two forty two prescriptions are 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 going to come first and we initiated these interactions and promotional activities as soon as we got label. So, they're a reflection of the work that we've done for the whole quarter. In the first month, we didn't have the ramps 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 day to start prescribing, they did start prescribing.

35:38 We are very pleased with what we are seeing right now because the prescriptions are coming from a very healthy geographic breadth. They are coming from the community prescribers, majority where the majority of the patients are managed right now, and we see this 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. So, 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.

36:36 And Mark, on the second part of your question about the ten to twelve weeks that Staatta commented on in her prepared comments, we have been encouraged that these motivated patients have translated to therapy faster than that in some cases. But again, this is relative to the motivation of both the physician and the patient. And 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 perhaps a mitigating factor on the enthusiasm aspect, and it might take a little bit longer for those patients to convert to therapy. Okay, you completely understand that, but maybe just to push on a little bit, 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.

37:38 Yep. But I guess it sounds like you expect it to be counter out more than counteracted by that kind of difference in enthusiasm from the patient itself. Yep, we'll definitely the team is doing an excellent job right now and we haven't had any payer hurdles 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 six months on average to get the port payer policies in place. But as of now, similar to patients and physicians, payers have been very receptive of the profile and market access has not been a hurdle. Okay. Thanks a lot and congrats on all the progress. Thanks, Mark. Thank you. And our next question will come from the line of Salveen Richter from Goldman Sachs. Your line is open.

38:29 Hi, this is Lydia on for Salveen. 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? And are you still seeing a majority of prescriptions coming from the community hem oncs? And is the team starting to engage with physicians beyond those who were targeted ahead of the launch? Thanks so much. Yes, 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. And that's driven by the fact that patients with thalassemia are actually managed mainly in the community setting.

39:19 We see prescriptions coming from across the country, which is fantastic. And as we move forward, the patients will continue to increase the breadth of prescribing. And of course, we'll focus on that as well. But the majority of the business is going to continue to grow breadth. Thanks so much. You. And our next question will come from the line of Tess Romero from JPMorgan. Your line is open. 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.

40:05 You know, ultimately, what do you see as the implications of Novo's recent results to next steps at Agios? And how does this change your view of what you need to see to drive tebipivat forward in sickle cell disease as well? Thanks Tess. Sarah can start with our focus on mitapivat and then we can comment on tebipivat as well. Sure. Hi, Tess. So we haven't seen the full hibiscus results yet. So as Feda highlighted, I mean, we see a clear commercial opportunity in sickle cell disease with mitapivat. As she highlighted, there is room for multiple players given the prevalence and the disastrous nature of this disease.

40:58 And 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. So, there is really a lot of excitement for our drug in the community both by patients and physicians. And 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 into Q2.

41:51 So, we are very pleased with where we are. Okay. Great. And 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? Well, yes, obviously, like the data is, you know, very limited right now that we have to our availability. So, anything as it relates to standard study metrics, would love to see. Okay. Thank you. Thank you. Thanks, Gus. And our last question will come from the line of Greg Renza with Truist. Your line is open.

42:40 Hi, team. This is Safot on for Greg. Congrats. And may I add a congrats to the launch, Stella. One question on Agovesmi. So with the momentum continuing to build, you have two forty two prescriptions in the first quarter. Are you starting to see any early signals of patient persistence, patients staying on therapy, given that this is a chronic setting? And any differences in the patterns between transfusion dependent versus non transfusion dependent? And I have a follow-up. 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 for a month of therapy to start seeing more the continuation rate.

43:32 But we've seen pyrokines in PK deficiency performing extremely well in the real world. We expect to see the same strong performance in thalassemia as well. Sometimes we talk about the REMS as kind of paperwork and work, but actually it helps with the frequent interactions between patients and physicians and actually can support continuation of therapy as well. So we'll wait and see that's one very important factor we'll continue to monitor. Got it. Thanks. Thanks, sweater. And a second question on mitapivat in sickle cell disease. So assuming accelerated approval, how do you think about the opportunity for early uptake based on hemoglobin as appropriate endpoints and potentially on the label while additional outcomes data are being generated in a confirmatory study, and especially in light of etavolpivot hitting the VOC endpoint?

44:34 Yeah, this a little bit reflective of what Sarah had commented on as well, that sickle cell disease has very high unmet need. And as Sarah said, it's a multidimensional disease. There are many things to address clinically within sickle cell disease, And we stand proud and tall with rise up data that we've seen, particularly as well the responder analysis. Sted and her team are, of course, already preparing commercially for that potential opportunity ahead with the accelerated approval pathway. And just if may add, the data from Rise Up that we've highlighted to physicians and to patient communities has been very well received.

45:24 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 might that compare to the potential VOC data that we might see in hibiscus, you know, just when it comes to treatment selection? Yes, so thanks. So, the endpoint as highlighted is informed by the rise of data set in which we've collected data systematically, prospectively. So, we've had also great engagements with the FDA, and that has progressed very nicely. So, again, we are now able to speak to our intent to file in the second quarter.

46:18 We've also highlighted before that we will be presenting data at or around EHA around all of the data, 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 hopefully be able to put that data into label at the time of approval when the results allow.

47:07 So, we are very excited about where we currently are. We have really, you know, great confidence in our data in the path that we are on. Got it. Thanks and congrats again. Thank you. Thank you. And this concludes the question and answer session. I would now like to turn it back over to Brian Goff for any closing remarks. 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 AKVESBI in thalassemia, as we've discussed, to continued advancement toward imidipivat sNDA filing in sickle cell disease and to maintaining a disciplined financial approach with multiple meaningful catalysts ahead this year.

47:59 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 twenty twenty six EHA Congress. So thank you very much, everyone. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.