Good morning, and welcome to Agios Pharmaceuticals' fourth quarter and full year 2025 conference call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Morgan Sanford, Head of Investor Relations at Agios. Please go ahead. Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' fourth quarter and full year 2025 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 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. Thanks, Morgan. Good morning, everyone, and thank you for joining us on today's call. Next slide, please. Just last month, we outlined our 2026 strategic priorities, which are focused on delivering long-term shareholder value. First, we're focused on executing a high-impact launch of Pyrukynd for the treatment of thalassemia in the U.S. Second, we see meaningful opportunity to expand our PK activation franchise into additional high-value indications, including sickle cell disease and lower-risk myelodysplastic syndrome, with key catalysts this year for both opportunities. Third, through the advancement of our early-stage pipeline with AG-236 and AG-181, we have the potential to unlock future value in hematologic and other rare diseases. And finally, we remain committed to long-term sustainability, supported by disciplined capital allocation and continued operational efficiency. Building on those priorities, the next slide maps key pipeline catalysts in 2026 across multiple high-value indication opportunities. The ACTIVASE launch in thalassemia is underway in the U.S., and we look forward to the potential to expand our PK activation franchise into sickle cell disease and lower-risk MDS. These milestones and continued progress in our early-stage pipeline position the portfolio for growth and long-term value creation. Next slide, please. We exited 2025 with solid momentum across the business, commercial execution, pipeline progress, and continued focus on financial discipline, which together provide a strong foundation to deliver on our 2026 strategic priorities. Starting with commercial performance, PYRUKYND delivered $20 million in net revenue in the fourth quarter, bringing full-year 2025 revenue to $54 million, reflecting robust year-on-year growth. In the fourth quarter, we reported top-line data from the RISE UP phase III trial, and will meet with the FDA this quarter, as anticipated, for our pre-sNDA meeting to determine the regulatory path forward. Importantly, just before the end of the year, we received FDA approval for ACTIVASE, and the U.S. thalassemia launch is underway. Finally, we recently completed enrollment in the phase II sickle cell disease trial of tebapivat, with top-line results expected in the second half of this year. Importantly, we continue to operate from a position of strength, ending the year with approximately $1.2 billion in cash, providing flexibility to maximize the ACTIVASE thalassemia U.S. launch, pursue the path forward for mitapivat in sickle cell disease, and continue to advance our pipeline programs. Please move to the next slide, and I'll turn the call over to Cecilia to provide additional details on our 2025 fourth quarter and full year performance, as well as our 2026 outlook. Thank you, Brian. Next slide, please. Our fourth quarter and full year 2025 financial results can be found in the press release issued earlier this morning, and additional details can be found in our 10-K, which will be filed later today. Fourth quarter worldwide PYRUKYND revenue was $20 million, an increase of 86% compared to the fourth quarter of 2024, and a sequential increase of 55% compared to $13 million in the third quarter of 2025. In the U.S., fourth quarter revenues of $16 million were driven by continued commercial focus in PK deficiency ahead of FDA approval for ACTIVASE, an additional ordering week in the fourth quarter, and favorable growth to net adjustments. In 2026, we expect U.S. PK deficiency revenues to be in the range of $45-$50 million. Outside of the US, revenue of $4 million in the fourth quarter primarily reflects inventory stocking ahead of demand-driven by PK deficiency patients in Europe, transitioning from our global managed access program, where PYRUKYND was provided free of charge, to commercial supply. We anticipate a sequential decline in ex-US revenues into the first quarter of 2026. Cost of sales for the fourth quarter was $1.9 million. R&D expenses were $88.1 million, an increase of $5.3 million compared to the fourth quarter of 2024, associated with the advancement of our earlier-stage pipeline program. SG&A expenses were $51.6 million in the fourth quarter and roughly flat year-on-year. We ended the fourth quarter with cash, cash equivalents, and marketable securities of approximately $1.2 billion. As a reminder, in future quarters, we will report mitapivat revenue as a whole, breaking out U.S. and ex-U.S. performance. Next slide, please. We remain committed to financial discipline as we work toward our goal of becoming a sustainable rare disease company. We anticipate operating expenses in 2026 to be roughly flat with 2025. This guidance assumes investment to maximize launch of ACTIVASE in thalassemia in the U.S., gated investment for sickle cell disease, and operating model refinement. Importantly, we see a clear path to profitability through our existing commercial presence in thalassemia and PK deficiency. Please advance to the next slide, and I will turn the call over to Tsveta to share commercial highlights for the quarter. Thank you, Cecilia. Next slide, please. As Cecilia noted, in the fourth quarter, PYRUKYND delivered $60 million in net revenue in the US, up 50% year-over-year, driven by continued demand in PK deficiency, an additional ordering week in the quarter, and certain gross-to-net adjustments. Fourth quarter ex-US revenue was roughly $4 million, which primarily reflects supply ahead of demand pull-through, as PK deficiency patients in Europe transition onto commercial supply. We expect this ordering to moderate in coming quarters. As expected, we continue to see quarterly variability driven by ordering patterns, inventory dynamics, and gross-to-net adjustments. Fourth quarter performance underscores the strength of our commercial model and the foundation we are building for future growth, starting with the recent US approval of ACTIVASE for the treatment of anemia in adults with alpha and beta thalassemia, regardless of transfusion burden. Please move to the next slide. I am pleased to share that, as planned, the final implementation of PYRUKYND REMS was completed in late January to align with the approved FDA label, and we have already begun dispensing products. As of January thirtieth, we have seen 44 prescriptions written by REMS-certified physicians in the US, which reflects strong early recognition of PYRUKYND's clinical value and excellent execution by our field teams. What is especially encouraging is the healthy breadth of early prescribers at this stage of the launch, with its strong geographic distribution and, as expected, predominance of community physicians as early prescribers. We are also seeing, in these early days of launch, emergence of the patient profile we anticipated, largely transfusion-dependent patients, along with a group of highly engaged non-transfusion-dependent patients. These early signals speak not only to our launch readiness, but importantly, to our deep understanding of this patient community and their unmet needs. Please move to the next slide. We are very encouraged by the early market response to ACTIVASE. Physicians consistently view its profile as addressing meaningful gaps in the current treatment landscape for thalassemia. Importantly, this aligns with what we heard ahead of FDA approval. We are not seeing the REMS as a barrier to prescribing, with early experience suggesting the certification process has been straightforward. We have also seen strong engagement with our patient support program. Initial experience indicates that patients do not view the REMS as burdensome, given the potential for meaningful clinical benefits, including reduction in transfusion burden and improvement in fatigue. Taken together, this early feedback reinforces both the significant unmet need in thalassemia and the value proposition of ACTIVASE. It also reflects the strength of our pre-launch planning. On the next slide, I will take a few moments to discuss how we anticipate this demand will convert into treatment initiation and ultimately revenues in the first few quarters of launch. There are three key steps in the ACTIVASE REMS certification process. One of those steps, pharmacy education and certification, is already completed, as we use a single specialty pharmacy to dispense prescriptions and coordinate on delivery. Additionally, physicians are required to be educated and certified on the ACTIVASE brand. In parallel, once a prescription has been written, patients need to receive insurance authorization and complete a baseline liver test prior to initiating treatment. Our comprehensive patient support service, My Agios, has a strong track record assisting patients with the insurance authorization process for PK deficiency, which we expect to continue with thalassemia. Once these three components are completed, the pharmacy is authorized to dispense the prescription. Patients will then complete monthly liver tests for the first six months and as clinically indicated thereafter. Initially, we expect the time from prescription to treatment initiation to be on average 10-12 weeks. As physicians are onboarded and access expands, we see opportunity to shorten this timeline as launch progresses. Turning to the next slide. The thalassemia opportunity presents a major potential growth inflection for Agios. To date, we have received approval of mitapivat for thalassemia in two regions, marketed as ACTIVASE in the US and Fyrokind in Saudi Arabia. Our capital-efficient global commercial model enables us to focus our investment on the US, which presents the most significant revenue opportunity. Outside of the US, we have executed commercialization and distribution agreements with Advanz Pharma in Europe and NewBridge Pharmaceuticals in the GCC. Given access dynamics, we currently distribute Fyrokind in Saudi Arabia on a patient-by-patient basis, with potential to expand access following national procurement agreements. In Europe and UAE, regulatory reviews remain underway. We anticipate a potential EC decision in the coming months following the positive CHMP opinion received in October 2025. Across these regions, we see real potential to expand access and deliver meaningful growth as we scale the launch globally. Please move to the next slide, and with that, I will hand the call over to Sarah to cover key R&D highlights from the quarter. Thank you, Tsveta. Next slide, please. Since we reported third quarter results, we have continued to make progress advancing our robust rare disease pipeline. We received the FDA approval of PYRUKYND for alpha and beta thalassemia, regardless of transfusion burden, on December 23 of last year. As you heard from Tsveta, the US launch is underway with strong reception from physicians. Following the RISE UP phase III top-line data of mitapivat in sickle cell disease, we will have our pre-sNDA meeting this quarter to inform the regulatory path forward. We continue to advance our more potent PK activator, tebapivat, in two phase II trials and anticipate results in lower-risk MDS in the first half of this year and in sickle cell disease in the second half. We continue to advance our early-stage pipeline to important decision points this year and are on track to initiate a phase Ib proof of mechanism trial of AG-181, our phenylalanine hydroxylase stabilizer in PKU patients in the coming months, and report top-line data from the phase I healthy volunteer study of AG-236, our siRNA targeting TMPRSS6 for polycythemia vera in the first half. Please move to the next slide. Turning to tebapivat, we look forward to understanding more about the potential role of this more potent PK activator in low-risk MDS and sickle cell disease this year. We remain on track in low-risk MDS, where top-line data from the phase IIB trial are expected in the first half of this year. This study will provide important insights into dose optimization, as well as the potential role of tebapivat in different patient subgroups, including low and high transfusion burden patients, as well as potential applications in later lines of treatment. In sickle cell disease, enrollment in the phase II trial is now complete, an important milestone that reflects the growing enthusiasm for PK activation following the RISE UP phase III results of mitapivat in this debilitating and deadly disease. This 12-week double-blind trial is designed to further explore tebapivat's potential to deliver meaningful improvements in hemoglobin, as well as broader markers of hemolysis. In turn, we see potential for higher hemoglobin response, building on the strength of the data established with mitapivat. Together, these programs underscore the potential for tebapivat to expand our leadership in hematology and address multiple high-value populations where unmet need remains significant. We have an exciting year ahead of us, and we look forward to updating you on our pipeline progress throughout the year. 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. In closing, we have another pivotal, catalyst-rich year ahead of us. In line with our 2026 strategic priorities, we're focused on executing a high-value ACTIVASE US launch in thalassemia. In sickle cell disease, we're preparing for our pre-sNDA meeting for mitapivat this quarter, an important step toward defining our regulatory path. We also expect phase II top line data for tebapivat in sickle cell disease later this year, which will give us deeper insight into the potential of higher potency PK activation in this population. In lower-risk MDS, phase 2b top line data for tebapivat remain on track for the first half of 2026 and will be a key readout as we assess its ability to drive transfusion independence and broader improvements in anemia. We also anticipate phase I top line data for AG-236 in polycythemia vera, and phase 1b proof of mechanism data for AG-181 in PKU, two important early-stage programs that expand our reach across hematologic and other rare diseases. Please move to the next slide. As we look beyond 2026, our opportunity set continues to expand. The combined global market potential across our current pipeline indications exceeds $10 billion, reflecting both the breadth of unmet need and potential to deliver transformative medicines to patients. Beginning in 2026, we're focused on delivering a high-impact US launch of ACTIVASE and thalassemia, which we believe has the potential to establish a strong foundation for our leadership more broadly in rare hematology. Our combination of near-term catalysts, disciplined investment, and a maturing pipeline creates a clear pathway to deliver long-term value. Agios is well positioned for the next chapter of growth while advancing the next wave of innovation across our rare disease portfolio. Before we move into Q&A, I'd like to acknowledge the dedication of our employees, whose unwavering focus and commitment continue to make a meaningful difference for patients with rare diseases. With that, I'd like to open the call for questions. Operator, please open the line. Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from Gregory Renza with Truist. Your line is open. Great. Thanks. Good morning, Brian and team. Congrats on the quarter and, of course, another eventful year. Maybe two questions from us on ACTIVASE and then on sickle cell. First, just on the ACTIVASE launch, we appreciate all the color you are sharing early and getting patients engaged and prescriptions written. Just on that translation, perhaps on the prescription updates that we are seeing, how do you see that not only translating to treatment initiation, but also to revenue recognition? Maybe not asking for guidance on early quarters, but any color you can provide on the first quarter and even subsequent early days of the launch with respect to how it bolstered revenue. And then I have a follow-up. Thanks. Yeah. Thanks, Greg. Very happy to talk about the launch. And before Tsveta gets going here, I just want to say I'm really proud of the way the team has executed its early days, but Tsveta is excited to finally have a chance to begin talking about the ACTIVASE launch. Absolutely. Definitely excited. Greg, as I mentioned in my prepared remarks, we are really encouraged by the early demand that we're seeing with ACTIVASE. As you mentioned, we reported that we had 44 prescriptions from REMS-certified physicians up to January thirtieth, which is the first five weeks of the launch, and that is fantastic to see. With regards to your questions, what we expect is to see in the initial quarters, prescriptions and demand to grow ahead of revenues. And the main reason for that is that it takes about 10-12 weeks for us to convert prescriptions to treatment initiations and ultimately, revenues. We anticipate in Q1 the majority of the prescriptions to turn into treatment initiation, and as the year progresses, we'll expect to see revenues and demand to start tracking more closely. We get a lot of questions about potential analogs. So when I think about another product which also has a liver REMS, that's Filspari. So that's a good analog for you to look at, of how the actual revenue trajectory throughout the first year of the launch actually evolved. It's a very different disease, of course, but from a shape of the curve of the revenue, I think it, it's a good one to look at. Great. Thank you. That's very helpful. And maybe just moving on to sickle cell and tebapivat, and of course, not to overlook the MDS readout in the first half. But you know, with enrollment complete in the phase two in sickle cell and Sarah, the color that you've provided, maybe if I may just ask a bit about how you're pegging expectations for what you want to see to get excited about the phase two data in sickle cell coming later this year. You've spoken about the potency and the higher hemoglobin response potential, but any color that would help to get you excited and how that kind of fits into the larger portfolio relative to mitapivat and the larger sickle cell space even. Thanks so much, and congrats again, guys. ... Thanks, Greg. Sarah? Thanks, Greg. So yes, thanks for the question, Greg. So the phase 2 tebapivat trial that we've just indeed announced full enrollment is a dose-finding trial, so we are looking indeed to explore the doses. We are looking at the hemoglobin response. It is a standalone phase 2 trial, so our VOCs are included as safety assessments. It's different than how the phase 2/3 seamless operational design was for RISE UP. But obviously, we're now in a position that we can leverage data across PK activation franchise, basically, and we're able to use the RISE UP data to also model what we anticipate a hemoglobin response can lead to for clinical benefit. So we're very excited about the trial. We think actually the fact that we can announce the enrollment completion also reflects the excitement of the community. You know, the RISE UP data announcement really led to a faster enrollment in the tebapivat phase II trial, so we are very excited about that. Thank you. Our next question comes from Samantha Semenkow with Citi. Your line is open. Hi, good morning, and thanks very much for taking the questions, and congratulations on all the commercial progress. Just one follow-up on ACTIVASE. I'm wondering if you could speak to a bit of the cadence of scripts that have come in since approval, and particularly, are you seeing an increase in the scripts written since January thirtieth, after the REMS has become fully operational? And then just a second question. I'm wondering if you could speak to the potential outcomes from the planned sNDA meeting with FDA on the sickle cell disease. What are the outcomes that could come out of that meeting? Thanks very much. Thanks, Sam. So we're gonna stick with the 44 that we have so far for ACTIVASE, but I think Tsveta could continue to provide color on, you know, the early days of the launch. So I'll have Tsveta start on that, and then Sarah can speak to the pre-sNDA meeting. Absolutely, Sam, and a reminder, we started basically engaging and educating physicians and generating demand as soon as the product was approved. So within the first five weeks of the launch, we've been educating physicians on the value proposition of ACTIVASE and the REMS itself. So we are very encouraged with what we see in terms of demand in these early stages of the launch. A lot of the things that are happening, and I'm really, really pleased with the execution of the team, are happening as we expected. So we are seeing prescriptions coming from the transfusion-dependent patients and the very engaged, symptomatic, non-transfusion-dependent patients who have frequent interactions with the healthcare system, which is fantastic. And we see a very healthy dynamics of the launch in terms of the physicians prescribing. We see prescriptions coming from across the country, and a lot of them are in the community setting, where the majority of the patients are treated, and I'm really pleased with the progress that the team is making. Great. And then, Sarah, the pre-sNDA meeting and Sam's question about the potential outcomes. Yes, thanks, Sam. So, we've guided to the pre-sNDA meeting in the first quarter of this year. The goal for that meeting is, of course, to gain insights in the regulatory pathways that we can use for mitapivat. As stated, we are, of course, going in with a data package that we would like to present for full approval based on the data that was generated in RISE UP with, you know, the strong anti-hemolytic profile that is now confirming again the anti-hemolytic profile of mitapivat now in a third hemolytic anemia with additional strong clinical benefit observed in those hemoglobin responders. And once we have that meeting, like, we are planning to give an update or when we have the meeting minutes to you guys. Great. Thanks very much. Thank you. Thank you. Our next question comes from Alec Stranahan with Bank of America. Your line is open. Hey, guys. Thanks for taking our questions. Great to see the continued progress for both the commercial and the clinical stage portfolios. Two questions from us. I guess first, what is sort of the main bottleneck in forming that 10- to 12-week prescription to treatment initiation? Is it getting the patient in for their baseline liver test or maybe something else? And how do you anticipate this shortening over the course of this year? And then second, for tebapivat in MDS, what does good look like on transfusion independence in this lower-risk population? And I guess, given what you learned from the phase IIa, do you expect you could see activity at the 10 mg dose based on sort of the emerging PK data, or is this maybe more likely at the 15 and twenty mg doses? Thank you. Thanks, Alec. So we're gonna follow the same sequence here. Tsveta gets to talk about the ACTIVASE launch, and then Sarah, thankfully, we've have a robust pipeline, so she can discuss the MDS trial with tebapivat. Absolutely. So the 10-12 weeks is driven by two things. The first aspect is the insurance authorization, which is very standard for any specialty rare disease drug. That's not unique to ACTIVASE. And most of the patients would need to go through prior authorization, which can take, you know, on average, a month, and for some patients, it happens faster. For some patients, it takes longer, but that's one of the main drivers. The second aspect is the requirement for a liver test ahead of the treatment initiation. So when we combine both of these factors, we anticipate the conversion from prescription to treatment initiation to be on average, 10-12 weeks. As I said, we'll see kind of patients falling on either end of that time frame. And over time, we'll of course look to shorten the time from prescription to treatment initiation on both fronts. We have an excellent market access team that will be engaging with payers. So as some of the payers actually put the product on formulary, that can be an opportunity for us to move faster through some of the prior authorizations and supporting patients, as well as we'll be learning throughout the launch and identify areas to support patients to have an efficiency in their liver testing initially as well. Great. And Sarah, for tebapivat in MDS, just some of the, you know, what are we expecting? And then the different dosing. Yeah, thanks, Alec. So to your point, we indeed are testing higher doses than the dose that we tested in the phase 2a. So we have a 10 milligram, a 15 milligram, and a 20 milligram dose. So indeed, we are looking to explore the doses here in this phase II to see which dose would be best. And then in addition, we are because it's a heterogeneous patient population, this trial will also allow us to further define patient populations. So we have low and high transfusion burden plus additional lines of therapy that have been used. So it will really give us a lot of insights on where this drug can play a role. Obviously, it's an oral therapy, which of course, can be very meaningful for a patient population like this, because, if patients would have treatment response, it allows them to be really untethered of the clinic. Yeah, it's gonna be... It's an exciting year for tebapivat. In 2026, we have 2 catalysts. As we noted, we have the MDS phase 2B trial in the first half of the year, and then, as we've already discussed, for sickle cell disease, the second half of this year, we look forward to that phase II result. Great. Thanks for the color, and congrats on the continued progress, guys. Thank you. Thank you. Our next question will come from Mark Breidenbach with TD Cowen. Your line's open. Hi, thanks for taking my question, questions. Maybe to start on ACTIVASE with the REMS-certified physicians. Just can you maybe talk about kind of where that is from a quantitative perspective, you know, within these first few months? And kind of what do you think that trajectory looks like in terms of number and breadth of certified physicians over the next, you know, quarter or two as that part of the ramp really happens? And then I'll have a follow-up on the pipeline. Okay, you can start. Yeah. When it comes to the REMS, in this initial stage of the launch, I'm really pleased with what we are seeing, and things are happening exactly as we anticipated. Physicians don't see the REMS as barrier to prescribing, and the patients that we've engaged with, they basically don't see it as burdensome, given the strong value proposition of ACTIVASE and their willingness to consider and initiate therapy. What is happening with the REMS? Initially, a lot of the bigger academic centers and care worlds are getting certified, and when it comes to the community physicians, actual certification happens almost simultaneous with the first prescription. And we will see in a way, the certification and REMS progressing simultaneously over time. But as I said, REMS hasn't been a reason or a reason for not to prescribe. It's the opposite. When physicians have patients that they wanna initiate, they're more than willing to start to complete the REMS, which can actually take one visit. It's a very quick process. Great. Thanks. That's helpful. And then maybe just following up on Sarah's comments about the pre-sNDA meeting, and that the package is really aimed for supporting full approval. I think at other times you've also mentioned possibilities of an outcome of accelerated approval. Is that still something you think is a reasonable outcome, or are you, you know, more confident in a full approval than maybe you have been as you've gotten a little deeper into the data and conversations? And then assuming accelerated is on the table, yeah, what's your latest thoughts on kind of what a confirmatory trial might look like under that scenario? Yeah. So thanks, Mark. So for us, the data package, really, the benefit risk profile generated in RISE confirms a strong anti-hemolytic profile, as I mentioned, and we really see those clinically meaningful changes in the hemoglobin responders. So our view is that benefit risk here is, you know, seen in this trial, and it's a supplemental NDA. Now, as you also know, at ASH, recently, the FDA highlighted that hemoglobin can be a surrogate endpoint for sickle cell disease. So either one of those pathways for us allows us to discuss the data and have that meaningful conversation with the agency under any of those circumstances. Then there's always the normal filing procedures that one would have to go through. But we're very excited about the data as it stands. In regards to your question on confirmatory trials, obviously, we have several options that we can discuss, in which some of these options have endpoints that have been used before. Some of them are novel endpoints as well, so we're ready to discuss as needed. Okay. Thank you. Thank you. And our next question will come from Eric Schmidt with Cantor. Your line is open. Hey, guys. Sorry for any background noise, but Cecilia mentioned a direct path or clear path to profitability. I was hoping you'd get a little bit more detail on thinking around the breakeven point of revenue needed to hit that and maybe timelines to profitability. And then were there any sales at all in the GCC countries in Q4? Thank you. So we have, Thanks, Eric. We gave the guidance on profitability with PKD and thalassemia, regardless of the path forward for sickle cell. Kind of as our base case there. We haven't given specific timing of when that it will happen. We believe, you know, thalassemia is a meaningful opportunity. We're excited about the initial stages of the launch. We also have, as you mentioned, ex US being part of that opportunity as well. And then part of that profitability path also requires us to proactively manage our OpEx as we navigate the multiple catalysts on the pipeline. We talked about tebapivat, but we also have our earlier programs, so we haven't given specific timing on that. My fault. Second. In GCC? And then for GCC, what we've seen, the ex US revenue we saw in Q4 is mostly driven by Europe, and that is in anticipation of demand, so that's why we guided to an expected decrease, Q4 to Q1. GCC, as a reminder today, is on an equivalent of a named patient, like, case by case, so you'll see some consistency quarter over quarter until we get to the point where we have more broad access negotiated over the next 12-18 months or so. Yeah, Eric, I'll just add, we're pleased with the partner we have in place in GCC with NewBridge. Tsveta and I spent some time in Saudi Arabia late last year and really got a kind of a street-level sense about how the team is doing, the enthusiasm from clinicians, as well as even at the Minister of Health level. And, you know, that's gonna take some time to build traction, but I think in the early days, we feel quite good about the opportunity. Thank you. You bet. Thank you. Our next question comes from Emily Bodnar with H.C. Wainwright. Your line's open. Hi, good morning. Thanks for taking the questions, and congrats on all the progress. I guess for the first one, can you give some color on the type of physicians who are initially prescribing Activase and whether they're mainly physicians who've used PYRUKYND in the past, or are you getting physicians who are more new to drug? And then on sickle cell disease, assuming you achieve alignment with the FDA, are you expecting potential approval in 2026? And can you maybe discuss some of the launch prep that you're planning to do this year ahead of approval? Thanks. Thanks, Emily. Tsveta, you want to start with ACTIVASE and the types of physicians in the early days? Absolutely. As I said, a lot of the early launch dynamics are playing as expected. The team did a fantastic job ahead of the launch, profiling and prioritizing accounts, so the initial prescriptions are actually coming from the physicians we anticipated to see prescribing. As I mentioned, Emily, they're primarily the community hemons, where a majority of the patients are, and these are physicians we've engaged with previously. We don't see that much overlap between PK deficiency and thalassemia, and that's because PK deficiency is an ultra-rare disease, so there are very few physicians who actually have experience with PYRUKYND through PK deficiency. And as I said, I'm very pleased with the start of the launch. It's a very healthy breadth of prescribing that we see across the country. Different physicians are engaged and really trying the product in the patients that they would think will benefit the most initially. Great. And Sarah, for sickle cell disease and- Yes. -potential timing. Yes. So Emily, we haven't guided to potential approval dates yet. We are now the first guidance we have given in this process is our pre-sNDA meeting, anticipated Q1. And then, in regards to the launch prep, I will ask Cecilia to comment. Yeah. So as a reminder, we didn't, and very similar to how we did thalassemia, we didn't build for sickle cell until we saw the data, and that's what we refer to when we talk about the gated sickle cell investments. We will look into that timeline and understand the path to start building investment there accordingly. Thank you. Our next question will come from Salveen Richter with Goldman Sachs. Your line is open. Good morning. This is Lydia on for Salveen. Thanks so much for taking our questions, and congrats on the updates. Is there any additional color you can provide on the split between the non-transfusion and transfusion-dependent patients, among these 44 scripts that have been written? And then, given scripts will be the key metric to watch, do you anticipate third-party services like IQVIA to accurately capture these scripts? Thanks so much. Tsveta? Yep. So the initial prescriptions, as I said, very much as we anticipated, come from a combination of transfusion-dependent patients. Obviously, a large proportion is transfusion-dependent patients and a very engaged symptomatic non-transfusion-dependent patients who are in an active interaction with the healthcare system. So when you think about the kind of evolution over time, as anticipated, I think we'll see initially more transfusion-dependent patients, but the scale-up of the launch will come from the non-transfusion-dependent patients later on. When you think about IQVIA, we have a single specialty pharmacy that distributes the product, so IQVIA will not be the right source for you to look at. It's just the information will not be available, and this is the reason that we're looking to provide you initially with prescriptions, revenue, as well as we gave you the guidance on PK deficiency, so you can see where the growth of thalassemia will be coming throughout the year. Thanks so much. Thank you. And our next question will come from Tessa Romero with J.P. Morgan. Your line is open. Hey, guys. Thanks so much for taking our questions this morning. So first one is just on Activase. Just can you just quickly touch on initial payer dynamics over the first couple of quarters here and remind us of payer mix? Just want to make sure that we're thinking about potential free drug the right way. And then second question, a bit of a housekeeping question here. If you are indeed approved in sickle cell disease, how does your SG&A line change? Just trying to think through what you might need to successfully launch a drug in sickle cell, from an expense perspective. Thanks so much. Okay. Thanks, Tessa. And, Tsveta can start on the payer aspects, and maybe we could also just remind our gross to net assumptions, too. I don't think we- Yep. Absolutely. So Tessa, I will start here. So the payer mix in thalassemia is quite similar to PK deficiency, with majority of the patients being under the commercial payer bucket. Very similar to PK deficiency in any other drug. Initially, the actual market access and payer authorization through it will happen through medical exceptions because payers would take time, about 6 months, 6-9 months, to actually start putting the product on formulary. We have a very experienced market access team that is very familiar of how to navigate the medical exceptions process, and so far, in these early stages of the launch, I must say, as expected, we haven't seen any payer hurdles at all. I think the value proposition of ACTIVASE speaks to itself, and the team is doing a great job in terms of those interactions. Brian asked to kind of comment on the gross to net ex assumptions. Given that we don't expect that to be a managed category, very similar payer mix to PK deficiency or gross to net net assumptions for thalassemia similar to PK deficiency, 10%-20%. And then on the SG&A question, Tess, as we think about it, so as I mentioned, we're gonna gauge and manage our spend based on the regulatory discussions and the timing. But if you wanna think about it, is we have an infrastructure that we have built for PKD and thalassemia that we would obviously leverage, but the scale of sickle is much bigger, so we would have to scale up those functions that we built, but we have a really nice foundation to build from. Thank you. Thank you. Thank you. Our last question, it will come from Luca Issi with RBC Capital Markets. Your line is open. Oh, great. Hi, team. This is Shelby on for Luca, and thanks for taking the question. Could you remind us what's the rationale for dosing higher in lower-risk MDS versus the phase II for sickle cell disease? And then maybe one more. Now that we have the label and REMS program for thalassemia, do you expect any read-through to sickle cell, and has it changed any internal expectations on the commercial opportunity there? Any color is much appreciated. Thanks. Yeah, I think we could start with MDS and the rationale for all three of the doses being higher than what we tested in the 2A, and then we'll talk a little bit about REMS and sickle. Yes. So for the rationale of higher doses, so we originally had a phase 2A with the 5-milligram dose based on modeling from the healthy volunteer trial, but we learned in that trial that MDS patients metabolize it faster, the drug, and so we pushed the dose higher in the phase 2B to do further dose exploration versus sickle cell disease patients who are exactly the same as healthy volunteers. So that is why we have those dose differences between those two indications. And then, Sarah, you could start on the sickle cell question about REMS and read- through, and Tsveta can certainly comment on how we see it commercially. Yes. So as you know, in the sickle cell disease program, we did not have the same observations as we had in thalassemia. So it is much more like the pyruvate kinase deficiency program, where we do not have a REMS, as you know, versus thalassemia, where we do have a REMS. So all of this actually does give us optionality. Our going in position based on the data observed is that that would not be needed, and we would propose something more like the pyruvate kinase deficiency path. Now, a read-through, if it would turn out to be a REMS, I'll hand that one over to Tsveta. Absolutely. Obviously, sickle cell disease is a devastating disease with high morbidity and mortality, no treatment options, so we see a meaningful commercial opportunity, assuming we have a label in the US, and the team will be ready to execute on it. We've got ready and executing successfully on the REMS for thalassemia. It gives us a very solid foundation to continue to execute, if we were to have something similar in sickle cell disease as well. Yeah, and I'll, I'll just take a moment to say, so Tsveta's team has continued to navigate through PKD as a launch, which is ultra-rare and certainly not, not the easiest of launches that began back in 2022. And now we have PYRUKYND off to, you know, a really good start in the first month of January. So I, I feel very confident the team in any scenario will be very well prepared. So I think that's our last question? Yes. Okay. Then, I will go ahead and close it down. I first, I just wanna thank everyone for joining us this morning. It's an exciting time for Agios. As you heard throughout the call, we're entering 2026 with quite strong momentum and really pleased that we're already seeing strong initial progress with the PYRUKYND launch in the US. We have meaningful clinical and regulatory catalyst ahead, as we've talked about, and we'll continue to operate with financial discipline. These near-term drivers, combined with our advancing pipeline, position Agios to deliver sustained growth and long-term value, and we very much appreciate your continued engagement and look forward to updating you on our progress throughout the year. Thanks a lot. Thank you. This does conclude today's conference call. Thank you for participating, and you may now disconnect.