Agios Pharmaceuticals, Inc.

Good morning and welcome to AGO's Pharmaceuticals Third Quarter 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 AGO's request. I would now like to turn the call over to Morgan Sanford, Head of Investor Relations at AGO. Please go ahead, ma'am.

Thank you, Operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' third quarter 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. Next slide, please. 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. Our third quarter earnings call agenda is shown on the next slide. Joining me on today's call are Brian Goss, Chief Executive Officer, Cecilia Jones, Chief Financial Officer, Sveta Milanova, Chief Commercial Officer, and Dr. Sarah Huynh, Chief Medical Officer and Head of Research and Development. Following prepared remarks, we will open the call for questions. With that, please move to the next slide, and 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 to discuss our third quarter highlights, beginning on the next slide. With steady progress and a focused strategy, we have a clear path to unlock long-term shareholder value. First, we have multiple high-value catalysts in the coming months that position pyrokine, our foundational TK activator, to achieve its multibillion-dollar potential across TK deficiency, thalassemia, and sickle cell disease. Following the FDA's recent request for a REMS program, our PDUFA date for pyrokine thalassemia supplemental NDA has been extended to December 7th. We are actively engaged with the FDA and are leveraging this additional time to strengthen our engagement with the thalassemia community and further refine our launch planning. Additionally, we look forward to sharing top-line results from the Rise Up Phase 3 trial of pyrokine and sickle cell disease by year end. Meanwhile, we continue to advance our early and mid-stage pipeline, which includes our other PK activator, Tebapivet, for lower-risk myelodysplastic syndromes, or MDS, and sickle cell disease, AG181 for phenylketonuria, and AG236 for polycythemia vera. Importantly, our strong balance sheet with approximately $1.3 billion in cash and investments positions us to invest in a disciplined manner to both support our potential U.S. launches and advance our rare disease pipeline. Our third quarter highlights are summarized on the next slide. In the third quarter, we reported $12.9 million in net revenue, underscoring the strong value proposition of pyrokine. In August, we announced approval for pyrokine in adults with thalassemia in Saudi Arabia, our first global regulatory approval for this indication. And earlier this month, we also received a positive CHMP opinion recommending pyrokine for marketing authorization in Europe for the treatment of adults with thalassemia. And lastly, we achieved a key R&D priority by completing enrollment in the Phase IIb trial of Tevapivet in lower-risk MDS, and we anticipate top-line data early next year. With continued momentum across our commercial portfolio and pipeline, our team has demonstrated strong execution and agility keeping us firmly focused on our mission to deliver transformative medicines for patients. That agility is a competitive advantage as we work to transform the treatment landscape for thalassemia and sickle cell disease. Feedback from these communities through our recent global engagements reinforces the critical need for treatment innovation. Please move to the next slide and I'll turn the call over to Cecilia to provide commentary on our third quarter performance and four-year outlook. Cecilia?

Thank you, Brian. Next slide, please. Our third quarter 2025 financial results can be found in the press release issued this morning. And additional details can be found in our 10Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Third quarter net pyracine revenue was $12.9 million, an increase of 44% compared to $9 million in the third quarter of 2024, and an increase of 3% compared to $12.5 million in the second quarter of 2025. Third quarter net revenue growth reflects continued commercial execution in PKD ahead of potential U.S. approval for thalassemia. Looking ahead, fourth quarter performance will benefit from an additional ordering week compared to the third quarter, and we anticipate Pyrocon net revenue will continue to reflect continued focus on PK deficiency ahead of potential approval for thalassemia in the U.S. On a full year basis, given the strong execution of our sales force to date, We anticipate net revenues in 2025 to show robust growth compared to 2024, although we recognize this growth is on a relatively small revenue base. Cost of sales for the quarter was $1.7 million. R&D expenses were $86.8 million, an increase of $14.3 million compared to the third quarter of 2024. This increase was primarily driven by increased clinical trial costs associated with our PK activation franchise. SG&A expenses were $41.3 million in the third quarter, an increase of $2.7 million compared to the prior year, driven by disciplined investment ahead of the potential commercial launch of Pyroclan in Salisbury. We ended the third quarter with cash, cash equivalents, and marketable securities of approximately $1.3 billion. Next slide, please. Our capital allocation strategy, backed by a strong balance sheet, enables strategic investment in future growth and delivery of our ongoing pipeline program. we have built a capital-efficient global commercial model, prioritizing our investment in potential U.S. launches, which represent the largest commercial opportunities. We have executed partnerships with Newbridge Pharmaceuticals in the GCC and Avanzonite Bioscience in Europe, both of which are structured as revenue-sharing arrangements that favor AGIOS over the long term. We will record our share of sales as net revenue. Second, we will continue to invest in our ongoing early and mid-stage clinical progress. And third, we are opportunistically looking for ways to expand and diversify our pipeline through internal efforts or externally sourced assets. In closing, I am confident that our balance sheet will enable us to continue to execute from a position of strength. Please advance to the next slide, and I will turn the call over to Sveta to share commercial highlights for the quarter.

Thank you, Cecilia. Next slide, please. In the third quarter, we delivered $12.9 million in BioKind net revenues, up 3% sequentially, once again reflecting strong execution by our commercial team. 262 patients have completed prescription enrollment forums, including 14 in the third quarter, representing a 6% increase sequentially. This has translated into 149 patients currently on therapy, up 5% from the second quarter. These results underscored the strength of our commercial model and the foundation we are building for future growth. We are well positioned to deliver on potential U.S. launches for thalassemia and sickle cell disease. Please move to the next slide. Let's turn to thalassemia and our global commercialization strategy for pyrokine. Following the three-month expansion of our PDUFA goal date to December 7, we remain confident in our ability to deliver a successful launch pending regulatory approval. This confidence is further reinforced by our recent engagement with physicians, patients, and advocacy groups, which I will touch on shortly. Outside of the U.S., we have implemented a capital efficient global commercialization strategy through partnerships with Newbridge Pharmaceuticals in the GCC and Avanzonite Bioscience in Europe. These partnerships allow us to retain full rights to pyrokine while preserving our capital investment for US launches. In August, we announced SFDA approval of pyrokine for the treatment of adult thalassemia patients in Saudi Arabia marking our first global approval for Thalassemia. Launch activities are underway in Saudi. Our partner NewBridge is providing early patient access on case-by-case basis with the potential to expand access after securing national procurement agreements over the next couple of years. In Europe, We anticipate a European Commission regulatory decision in early 2026 following the positive recommendation from the CHMP, and we are actively working with our partner, Avanzanide Bioscience, to refine our launch strategy. Please move to the next slide. In the U.S., there are approximately 6,000 diagnosed adult thalassemia patients. It is important to remember that thalassemia is considered a spectrum of disease, not a single phenotype. Patients range from those who require regular transfusions to those who are non-transfusion dependent but still face debilitating fatigue and meaningful complications over time. The goal of treatment across the disease centers on three key aspects. address patients chronic anemia and hemolysis increase their quality of life and reduce the risk of comorbidities that can be caused by primary or secondary iron overload care for these patients happens in both academic centers and community hematology practices and we're equipped to support both over the past year we have profiled and prioritized accounts across settings. We also engage prescribers where patients are managed and delivered disease education to them. Following the announcement of our PDUFA Go data extension, we have taken the opportunity to continue our engagement with the Palestinian community. Through these ongoing interactions, stakeholders consistently recognize the clear and compelling potential of pyrokines. Advocacy leaders and clinicians emphasize the magnitude of the unmet needs facing thalassemia patients and continue to stress the urgency for novel treatments like pyrokines. Additionally, it has become clear that providers have strong familiarity and experience with REMS across both academic and community settings, and do not view a potential REMS program as a barrier to prescribing. Our established rare disease infrastructure gives us a clear advantage in launching pyrokines in thalassemia. With high-touch patient services and a single specialty pharmacy model, we are well-positioned to execute swiftly and compliantly within a REM framework. The team is ready, and we look forward to potential tele-senior approval before year-end, and we are confident in our ability to deliver a successful launch. And with that, please move to the next slide, and I will hand the call over to Sarah to cover key R&D highlights from the quarter.

Thank you, Sveta. Next slide, please. In the third quarter, we continue to make strong progress across our pipeline. In early August, we announced pyrokine's approval for adults with thalassemia in Saudi Arabia. And earlier this month, we received a positive CHMP opinion recommending pyrokine for marketing authorization in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha or beta thalassemia in Europe. And we look forward to a final regulatory decision by early next year. Finally, our reviews remain ongoing in the United Arab Emirates and in the U.S., where we continue to progress towards our new PDUFA goal date of December 7. Beyond pyrotimes, we were pleased to announce enrollment completion in the Phase IIb trial of sebapivac for the treatment of lower-risk MDS. Sebapivac, our more potent PK activator, has the potential to be the first oral therapy to address anemia due to ineffective erythropoiesis in patients with lower-risk MDS. I will share more on this potential opportunity shortly. Please move to the next slide. As we approach the anticipated top-line results for the Phase III RISE-UP trial, I wanted to take a moment to highlight the significant need in this community, as well as our potential to deliver a disease-modifying novel treatment with spirochines. There are approximately 100,000 diagnosed adult and pediatric patients with sickle cell disease in the United States and a significantly larger number worldwide. Sickle cell disease remains profoundly underserved. The lack of suitable treatment options contributes to a high mortality rate that has in fact worsened with U.S. life expectancy in the late 30s, underscoring a significant opportunity for therapeutic innovations. Spirokind is a potential first-in-class oral therapy for sickle cell disease, targeting both hemolysis and basal occlusion through a unique PK activation mechanism of action, activating both PKR and PKM2 isoforms, decreasing 2,3-DPG, limiting hemoglobin S polymerization, and increasing ATP to support red blood cell health. Please move to the next slide. Guided by extensive engagement with the sickle cell community, we designed the phase 3 rise-up trial to align with clinical needs, positioning spirocytes to potentially reshape the treatment landscape for sickle cell disease. One of the two primary endpoints investigates hemoglobin increase, which addresses chronic anemia and thereby potentially reduces organ damage and improves how patients feel and function. Our other primary endpoint evaluates the reduction in annualized rate of sickle cell pain crises, which are linked to organ dysfunction, early mortality, and a decreased quality of life for many patients. Importantly, one of our key secondary endpoints will investigate potential improvement in fatigue, which is an overlooked symptom. In fact, chronic fatigue in sickle cell disease patients have been shown to be comparable to fatigue experienced by patients with other debilitating diseases like cancer and cystic fibrosis. In the trial, we will assess the improvement from baseline on the PROMIS fatigue 13A scale, a validated measure of fatigue for this population. We look forward to sharing top-line results of the phase 3 rise-up trial by the end of this year. Please move to the next slide where we present high level view of the trial design and statistical plan. As a reminder, since the trial includes two primary endpoints, the trial is positive if statistical significance is achieved on either one of the endpoints. The pre-specified statistical testing strategy allows testing of the key secondary endpoints if at least one of the primary endpoints is met, thereby preserving the opportunity to show benefit on other key features of the disease, including fatigue. We remain confident in pyrokine's potential to become a transformative therapy for sickle cell patients and underserved and unrepresented populations with significant unmet needs. Next slide, please. I'd like to take a moment to highlight our second more potent pyruvate kinase activator, sebapivap, which is being investigated in ongoing phase 2 trials for two rare disease indications, low-risk myelodysplastic syndromes and sickle cell disease. Low-risk MDS accounts for approximately 70% of all myelodysplastic syndromes. Symptomatic anemia is the primary concern for most patients. Therefore, the primary treatment goal is to improve quality of life by managing the underlying anemia caused by ineffective air to police. Decreased glycolytic activity has been seen in MDS patients where they may show decreased PK activity and an abnormal pyruvate kinase-hexokinase enzymatic ratio. Tebapivac is designed to correct red blood cell metabolism by increasing ATP production and normalizing the PK-HK ratio. Today, there are limited treatment options to address low-risk MDS, and we believe Tebapivac has the potential to be the first oral medicine to address anemia due to ineffective erythropoiesis. We completed the Phase 2 portion in November 2023 and progressed to the Phase 2B portion, which evaluates three higher doses than were evaluated in the Phase 2A portion. This trial will investigate 10 mg, 50 mg, and 20 mg doses of Cevapivac daily versus placebo over 24 weeks. Today, we announced that we achieved enrollment completion and we continue to expect top-line data in early 2023. We are also investigating cebapivac for the treatment of sickle cell disease. Enrollment remains ongoing in the Phase II trial, and we look forward to providing updates in the coming months. Please move to the next slide. We continue to advance our early stage rare disease pipeline with HE181, an oral PAH stabilizer intended for the treatment of phenylketonuria, and HE236, our siRNA selectively targeting TMPR6 for the treatment of polycythemia vera. Our first early stage program is HE181 for the treatment of PKU. There are 15,000 to 20,000 patients diagnosed with phenylketonuria in the U.S., where patient symptoms can range from mild to severe. Currently available treatment options have demonstrated limited efficacy or significant safety issues, leaving patients with a gap in treatment and limited to phenylalanine-restricted diets, therefore significantly impacting a patient's quality of life. Our phase one multiple ascending dose trial in healthy volunteers is currently ongoing, and we look forward to providing updates on this trial in the future. Our second early stage program is AG236 for the treatment of polycythemia vera, a rare hematologic disease that affects approximately 100,000 patients in the U.S. PV causes an excessive production of red blood cells, increasing blood volume and viscosity, and can result in thrombosis, cardiovascular events, or death. Current treatment options are limited to phlebotomy, hydroxyurea, and other psychoreductive therapies. However, these medicines do not effectively control hematocrit for more severe patients. We believe AG236 has the potential to address the remaining unmet need with a potentially improved safety and efficacy profile and less frequent dosing. Last quarter, we received IND clearance and dosed the first subject in the phase one trial in healthy volunteers and look forward to providing updates as the trial progresses. 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. In the third quarter, we delivered meaningful progress across our 2025 R&D priorities, once again showcasing our ability to execute swiftly and effectively. Looking ahead, the fourth quarter holds exciting milestones. We are sharpening our launch planning in anticipation of the new December 7th PDUCA goal date for pyrokine and thalassemia, and we expect to report top-line results from the Phase 3 rise-up trial of pyrokine in sickle cell disease by year-end. Please move to the next slide. Our fundamentals remain strong. Backed by a seasoned leadership team with a proven track record, we continue to advance our pipeline and deliver meaningful impact for the rare disease communities we serve, communities whose insights guide us and are vital to our success. We are operating from a position of strength backed by a balance sheet that not only supports our potential US launches and advancement of existing clinical programs, but also enables us to pursue strategic business development opportunities to further expand and diversify our pipeline and ensure we can create long-term shareholder value. Before we move to Q&A, I want to take a moment to recognize the continued dedication of our employees whose relentless focus and commitment continue to drive meaningful impact for patients with rare diseases. Their work together with the voices of the communities we serve, is foundational to our mission. As we look ahead, we remain resolute in our pursuit of transformative medicines, advancing innovation with the aim of delivering long-term value for both patients and shareholders. 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 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In fairness to all, we ask that you please limit yourself to one question and one follow-up. Please stand by for our first question. Our first question comes from the line of Eric Schmidt with Cantor. Your line is open. Please go ahead.

Thank you for the opportunity to ask a question. Maybe first, just on the thalassemia review process, it's been almost two months now since you got the PDUPA extension. Do you have a better sense of what type of a REMS program the FDA is interested in here? I know there's a spectrum of maybe more or less onerous REMS programs. And then just second follow-up question, I think both Cecilia and Brian mentioned actively looking for external assets what type of bd makes sense for the company at this stage and would you wait until the sickle cell readout to transact thank you yeah good morning eric thanks a lot for the question i'll have sarah take the first one and then uh i can pick up with the the external pursuit question and uh sarah let me turn it over to you

Yes, thanks, Eric, for the question. So in regards to REMS and label, as you know, the review is ongoing with our extended PDUFA date of, you know, December 7th. We, per process, don't comment on the details of REMS and the label. However, indeed, to your point, there are many different forms of REMS. And as you know, the REMS is requested because of hepatocellular so you can anticipate that it will include monitoring and some form of education.

Eric, on your second question, in terms of continuing to expand our pipeline, our pursuit really is not tied to anything in particular. I'm really proud of the work that the team does to cast the net wide and continue to look at a number of different opportunities. And this goes externally, but it's also organically internally to see if there are other indications, for example, that we should pursue. But again, that's not tied to anything per se. In general, I mean, our sweet spot, of course, is rare diseases. We look for therapies that have transformative potential for patients, early de-risking opportunities. If we're talking about earlier phase assets, And then I would say another opportunity would be if we find something that doesn't have to be first in class, but we always set the bar for best in class, which we feel very proud of with our current organic pipeline. So that work continues ongoing. And like I said, I'm really proud of the capabilities that our team has, both with internal opportunities as well as external. Thanks. Good luck with the upcoming readouts. Thank you very much. I'm excited for it.

Thank you. One moment for our next question. Our next question comes from the line of Alex Stranahan with Bank of America. Your line is open. Please go ahead.

Hey, guys. Thanks for taking our questions. Just a couple from us. It's been interesting to see how the different geographies have approached the risk of liver injury for mid-pivot and thalassemia. Maybe could you just remind us what sort of liver monitoring requirements are so far being required in Saudi and potentially in EU if it's approved as well? And do you think this could change depending on the US label? And maybe second, as a follow up, I'm curious how this monitoring requirement is changing maybe your commercial approach in these different areas. Thank you.

Yeah, thanks, Alec. Again, Sarah can start with the labeling so far. And I'll just preempt by saying the label we have right now, of course, At this point, it only exists in Saudi Arabia, and Sarah can comment on that. And then we're still in process with FDA. And in Europe, it's a CHMP positive opinion, but we're still awaiting the conclusion of that review in the coming couple of months and expect that by early next year. And then I'll have Steda comment in terms of the impact of some of these scenarios. Sarah, do you want to start?

So, in regards to the label, yes, indeed, for Saudi, it's in line with our proposal of once a month monitoring for the first six months, and that label is now available for the European Union. We indeed are very pleased that we received the positive CHMP opinion, which, you know, from their perspective, confirms the benefit-risk profile that we saw. We are, obviously, the label will only be final when you have the EC decision, so the details will become available at that point in time. And to Brian, Brian already mentioned it, but the U.S., the review is still ongoing.

Thanks, Sarah. And then Sveta comments on potential impact of ARAMs.

Absolutely. So, as we all know, there are very few treatment options for the thalassemia patients across the board. And with regard to non-transfusion-dependent and transfusion-dependent patients, we remain very convicted behind the strong benefit-risk profile of pyrokine for these patients. And that has been reiterated and confirmed by all of our stakeholders, including all the clinicians I've interacted with recently in the field. after the announcement of a REM for the potential US lab label. I can tell you the team is prepared for the launch. We are taking advantage of the additional time to continue the engagement with the community and do disease education. And when it comes to a REM in the US, we don't anticipate that to be a barrier to prescribing or have an impact on our commercial opportunity. Because we know that both the academic as well as the community, hematology, oncology practices, they have an experience with DRAMS. And when I connected both with academics and the community prescribers, they confirmed that to me and the team is confirming that in the field on a daily basis.

Great. Thanks for the color and looking forward to December.

Yeah, same. Thank you.

Thank you. And one moment for our next question. Our next question will come from the line of Emily Bodnar with HC Wainwright and Co. Your line is open. Please go ahead.

Hi. Good morning. This is Joey on for Emily. Congrats for a great quarter and for taking our questions. Shifting focus to Tevipivat, how are you guys looking at what would be considered positive data in LRMDS, given the data for these patter set and emittal set? And then a follow-up, could you also remind us of the Evanzanite strategy for the European thalassemia launch and how the cadence could look like for that? Thank you.

Yeah, thanks a lot. I think we're going to follow the same order of entry here, so Sarah can get started on that and how we think about the potential in low-risk MBS, which is a very high unmet need area with You know, this is classic across all of our diseases that we're pursuing very limited treatment options. And then Sveta can comment on Avanzonite and also probably tuck in some comments about Newbridge, too. We have two very valuable partners outside the U.S. Sarah, you want to start?

Sure. So thanks for the question. So in regards to the positive data for lower-risk MDS, So we're very pleased that we were able to announce enrollment of our face to be trial today. So more data will come the beginning of next year for our program. Obviously we are going to take the ecosystem around us in into account when we when we look at the data that this program will generate. But what is important I think is what Brian just mentioned. There is a huge unmet need for this patient population specifically as the goal for this population tends to be really also now more and more focused on quality of life. And as you know, like for PK activators, quality of life has been an important component of their benefit profile. So that is something that we were definitely hoping to deliver to.

Great. Thanks, Sarah. Instead of pivoting then to Avanzonite, and since you've also spent some time outside the U.S. recently in Saudi Arabia, maybe you can comment on New Bridge as well and the preparation of our partners.

Absolutely. So starting with Avanzonite, first of all, we are very excited about the potential EC decision and approval of pyroclan for thalassemia in Europe coming early next year. We're working very closely with the Vansomite team to refine our strategy for Europe. It's important to remember that in Europe, after a regulatory decision and approval, each of the countries needs to undergo a pricing and reimbursement process. So at the moment, we are going with Vansomite, assessing the market opportunities, prioritizing market where to submit for pricing and reimbursement first, But the pricing and reimbursement brought in the European countries can take 12 to 18 months. So just keep in mind that we wouldn't see the immediate impact of an approval on the commercial opportunity in Europe after an EC decision is announced. But we prioritize Avantonite as our selected partner because they have a very strong rare disease capabilities and expertise as well as the pricing and market access capabilities. And we look forward to continue to work with them to provide access to patients in Europe. As Brian mentioned, I actually had the opportunity to spend some time with the team in Saudi for the SFDA approval in August. And again, very similar team here in Saudi Arabia. We consistently hear the higher med need for tele-semia patients. strong excitement about the benefit-risk profile of pyrokines and the value it can bring to that community. But as a reminder, again, in Saudi Arabia, the process after approval starts with one-on-one requests from physicians for individual patients for pyrokines, early adaptation access and market access. And it's going to take about a couple of years until we get to the stage of a national procurement agreement, which will open up more broadly and see the commercial opportunity there.

Good. Thank you. That makes sense. Thank you for answering our questions. You're welcome.

Thank you. One moment for our next question. Our next question will come from the line of Mark Frum with TD Cowan. Your line is open. Please go ahead.

Thanks for taking my questions. Just back on the liver events, maybe just as you've continued to dose people and follow them for longer and longer, just comment on if any additional events have been observed across the PKR trials. And to the extent any have, have they continued to conform to the description before of occurring within six months? And importantly, the patient returning to baseline whenever they do stop mid-pivot as a result. And then maybe on the commercial side, I recognize it'll take quite a while to work through case-by-case access and actually get to revenue for any of those patients, let alone the reimbursement negotiations. But maybe can you comment on just any level of demand you're already seeing in the Gulf to kind of start that process?

Sure. Thanks, Mark. Sarah, maybe you could just start then with the question Mark has around the hepatocellular injury and have there been – additional cases that have met the pattern that we observed in thalassemia, and then Sveta again can talk about the green shoots, I could say, of demand so far.

Sure. So in regards to the observations that we had in the thalassemia program that allowed us to determine the hepatocellular injury risk for thalassemia specifically, So nothing has changed the way we have assessed the risk. So safety profile remains exactly the same as when we declared this hepatocellular injury risk. And we have not observed anything across the program that warrants us to update the safety profile the way we currently understand it.

Good. Thanks, Sarah. Sveta?

So, yes, I actually had the opportunity to meet with some key customers in Saudi Arabia this week in some of the biggest hospitals. And as I said, we definitely hear the interest in Virokind's profile, the desire to try it in individual patients and gain experience with the product. At the very beginning, in the country, it's a very burdensome process, which actually takes months from an individual patient prescription and request until approval at the hospital level and securing the budget. So we expect that to be the slow process, slow and steady. As the individual patients request get approved, the experience gets stronger and stronger, but definitely the interest from the community is there and it's high. It's just the process in the country takes time.

And Mark, what I would add is What's unique about Saudi Arabia is, of course, the prevalence is quite different from what we see in the U.S. on a per capita basis. It's about eight to nine times more common. So on the less rare side, for sure, most clinicians certainly have a good working knowledge of thalassemia. However, the common denominator that we see across all geographies really is a function of the limited treatment options available is the need for us to continue to educate, particularly the burden that non-transfusion-dependent thalassemia patients face on a daily basis because they're subjected to chronic hemolysis. And all the downstream consequences that come from that, you know, we're doing our part to make sure that clinicians have that top of mind as they think about the potential that that part-time could offer. So that's one thing that's not unique to geography. It's across all markets in the world. Okay, thank you. You're welcome.

Thank you. And as a reminder, to ask a question, please press star 1-1 on your telephone. One moment for our next question. Our next question comes from the line of Tess Romano with J.P. Morgan. Your line is open. Please go ahead.

Hey, Brian and team, thanks so much for taking our question. So for the phase three portion of Rise Up, has the last patient exited the trial yet? And what are any considerations in terms of the steps and timing to get to your top line? And then I have a follow-up.

Okay, well, I will allow Sarah to comment. I will just remind that we will not be more refined on our timing guidance for the Rise Up data that we're also eagerly awaiting We'll be more refined by saying that we're on track for that data by year end. Sarah, I'm not sure if you want to say anything additional about where we are in that process.

No, I think you summarized it, Brian. So indeed, like we're not commenting on individual patient status, but we are indeed on track to deliver the top line data by year end. And since we are very, like we have delivered several phase three clinical trials per our, you know, milestones. So we are a well-oiled machine at this point in time to get from database locks to top-line results.

Okay. And I'll just say, I mean, Tess, if I can just add, I am really pleased with the continued excellence and operations from the team because, of course, we have a lot of moving parts underway simultaneously. We have launch preparations. heard from svetta we've got sarah the team working on uh you know labeling for our paducah date that's approaching for thalassemia december 7th and then of course getting ready for a data readout for rise up so we're um this team is really delivering and i'm i'm really pleased with the operational okay so you can't tell us if your top line will be before or after your paducah date What an excellent follow-up question that I'm going to stick to by year end.

Okay. Thanks so much, guys.

You're welcome.

Thank you, and one moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open. Please go ahead.

Hi. Good morning, team. This is Lydia on for Salveen. Thanks so much for taking the question. Maybe just another one on the REMS program. Do you anticipate the requirements to apply kind of across the label to PKD and sickle cell as well? And have you received any physician feedback on how this might impact uptake, particularly with sickle cell where some of these treatment centers might not see, you know, PKD and thalassemia patients as well? Thanks so much.

Yeah, I think, Lydia, I might just start on this one to say, first of all, The REMS request has been specific to thalassemia, so that's an important point. And with respect to any potential outcome or impact, rather, in sickle cell disease, the most important step is what we literally just had discussed is getting to the point of the rise-up phase three data. That's the most important next step. And then from there, you know, we'll be better guided around the benefit-risk profile.

Helpful, thank you.

You're welcome.

Thank you. And I'm showing no further questions at this time. And I would like to hand the conference back over to Brian Gough for closing remarks.

Well, thanks, Michelle. And thank you very much, everyone, for joining us on this morning's call. As you've seen, and as I just mentioned, we've delivered on many of our milestones this year. So we have two of our most anticipated inflection points approaching by year end. As you can imagine, this is a very exciting time at Agios, and we truly believe that we are poised to deliver transformative new therapies for patients and create significant long-term value for shareholders. So thanks again, and we look forward to speaking with you again soon.

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.