Good morning, welcome to Agios's First Quarter 2023 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 this call is being recorded at Agios's request. I would now like to turn the call over to Agios's Chief Financial Officer, Cecilia Jones. Please go ahead. Thank you, Vera. Good morning, everyone, and welcome to Agios first quarter 2023 conference call. You can access slides for today's call by going to the investor section of our website, agios.com. On today's call, I am joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Gheuens, our Chief Medical Officer and Head of Research and Development, and Tsveta Milanova, our Chief Commercial Officer. Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result 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. With that, I will turn the call over to Brian. Thanks, Cecilia. Good morning, everyone, and thank you for joining us. Agios is the pioneering leader in PK activation and is dedicated to developing and delivering transformative therapies for patients living with rare diseases. We continue to generate consistent and compelling data with our PK activators across multiple disease areas, highlighting the potential of this differentiated mechanism of action to transform patient function, quality of life, and long-term outcomes in PK deficiency, thalassemia, sickle cell disease, and lower risk MDS. Driven by the enthusiasm of our clinical investigators and the operational excellence of our research and development team, I'm pleased to report that we have closed screening in our phase III studies in thalassemia, which together encompass the entire thalassemia population and expect to complete enrollment of these studies later this month. On behalf of the Agios team, I'd like to thank the patients, caregivers, and physicians for their continued participation in these trials. As Sarah will describe in more detail, the rapid enrollment of these studies highlights the significant unmet need in these areas and bolsters our conviction in our broader clinical development strategy. In this context, we continue to advance our robust clinical stage pipeline and are on track to announce the data readout from the phase II portion of the operationally seamless phase II, III RISE UP study of PYRUKYND in sickle cell disease and the go, no-go decision to phase III in the middle of this year. Echoing the positive reception of both PYRUKYND and AG-946 from investigators at our clinical trial sites, we continue to receive positive feedback from both patients and clinicians on the impact that PYRUKYND is having on individuals living with PK deficiency in the real world. We're encouraged to see that the efficacy of PYRUKYND observed in the clinical trial experience is translating to persistency on therapy in the real world, and we believe this has positive implications for the potential long-term impact of PK activation on how patients feel and function in not just PK deficiency, but also thalassemia, sickle cell disease, and lower risk MDS. Tsveta will provide a detailed update on our commercial performance in just a few minutes. As you'll hear from Cecilia, we ended the first quarter of 2023 in an enviable cash position with approximately $1 billion on the balance sheet. As a reminder, as part of the divestiture of our oncology business to Servier in April of 2021, we retained rights to a potential milestone upon FDA approval of vorasidenib and royalties on potential US net sales. We were therefore pleased to see that Servier's phase III trial of vorasidenib in patients with residual or recurrent IDH-mutant low-grade glioma met both its primary endpoint and key secondary endpoints. These data underscore Agios' strong track record in the discovery and development of therapeutics for disease areas with high unmet need, which to date spans five approved indications across three separate products. In addition to the upcoming phase II data readout of PYRUKYND in sickle cell disease, we're expecting a number of additional milestones by the end of the year, including completing enrollment of the phase III studies of PYRUKYND in thalassemia, enrolling more than half of the patients in the phase III ACTIVATE-Kids and ACTIVATE-KidsT studies of PYRUKYND in pediatric PK deficiency, completing enrollment of the phase II-A study of AG-946 in lower risk MDS, and filing the IND for our PAH stabilizer for the treatment of PKU. Finally, looking forward to what we expect to be a catalyst-rich next few years, we anticipate readouts from the phase III studies of PYRUKYND in thalassemia in 2024 and readouts from the phase III studies of PYRUKYND in sickle cell disease and pediatric PK deficiency in 2025. With that, I will now turn the call over to Sarah. Sarah? Thanks, Brian. In the first quarter of the year, our team made tremendous progress executing across our industry-leading pipeline of PK activators. We were pleased to receive the 2023 Citeline Award for Excellence in Rare Disease Drug Development. This award recognizes PYRUKYND's approval in PK deficiency and its significant potential impact in other hemolytic anemias, including sickle cell disease and thalassemia. Let me now provide a brief update on each of our programs, beginning with thalassemia, where PYRUKYND has the potential to become the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across all thalassemia subtypes. Specifically, the phase III thalassemia program comprises two randomized placebo-controlled trials, each of which is enrolling patients with both alpha-thalassemia and beta thalassemia. ENERGIZE is enrolling patients who are not regularly transfused with a primary endpoint of hemoglobin response. ENERGIZE-T is enrolling patients who are regularly transfused with a primary endpoint of transfusion reduction response. Reflecting our operational excellence in clinical development and our investigators' enthusiasm for the potential of PYRUKYND in this indication, we have closed screening in both ENERGIZE and ENERGIZE-T, and we expect to complete enrollment later this month and report top-line data next year. Turning to sickle cell disease, our goal is to address the high unmet patient need with an oral therapy that improves anemia, reduces sickle cell pain crises, and provides a durable improvement in how patients feel and function. To meet this differentiated target product profile, we are advancing the operationally seamless phase II, III RISE UP study of PYRUKYND in adults with sickle cell disease. The primary endpoint of the fully enrolled phase II portion of the RISE UP study are hemoglobin response and safety, and we are on track to announce the phase II data readout and the go/no-go decision to phase III in the middle of this year. This will be a data-driven decision informed by the protocol-defined go/no-go criteria in the phase II portion of RISE UP, including any additional data from the phase II secondary endpoint and longer-term data from the ongoing extension studies of the investigator-sponsored trials at the NIH and Utrecht University. Finally, we continue to advance the phase III ACTIVATE-Kids and ACTIVATE-KidsT studies of PYRUKYND in pediatric PK deficiency as we aim to deliver the first approved therapy for children living with this disease. We expect to enroll at least half of the patients in each of these studies by the end of the year. Turning to the development of AG-946, our novel PK activator that has the potential to strengthen our PK activator franchise and enable once-a-day dosing. As a reminder, lower risk MDS accounts for approximately 70% of MDS cases and shares an underlying pathophysiology with other disease areas in our pipeline. Based on the data we have generated in the phase I study of AG-946 in healthy adults, we look forward to progressing this study and expect to complete enrollment of the phase II-A portion by the end of this year. As we continue to advance the development of our PK activators, we also aim to expand our portfolio beyond PK activation through both business development and advancement of our earlier-stage pipeline. In this context, we continue to progress our small molecule, phenylalanine hydroxylase or PAH stabilizer program, to directly address the underlying cause of phenylketonuria. We are targeting an IND filing for this program by the end of this year. Overall, I'm excited by the tremendous progress the team made executing across our portfolio this quarter and look forward to a number of important milestones over the next several months. With that, I will now turn the call over to Tsveta. Thank you, Sarah. Our commercial organization is laser-focused on executing a comprehensive strategy that addresses each phase of the patient journey, from disease awareness to reimbursement, adherence, and persistency. By doing so, we aim to maximize the opportunity in the current launch in PK deficiency and build the capabilities needed to fully realize the potential of anticipated future launches in thalassemia, sickle cell disease, and lower risk MDS. A foundational element of any successful launch is a clear benefit/risk profile. Consistent with the positive feedback we received from patients, providers, we are pleased that the compelling data we observed with PYRUKYND in the PK deficiency clinical trial program has continued to translate into persistent treatment use in the real world. Specifically, our market research data indicate that nearly 100% of our target healthcare providers are likely to recommend PYRUKYND to their adult patients with PK deficiency. For clinicians, key drivers of these recommendations include improvement in hemoglobin levels, reductions in transfusion frequency, and impact on long-term disease complications and comorbidities. While we remain focused on patient identification and improving disease awareness, launch to date, discontinuations have remained low overall. Reauthorizations have not been a barrier, persistency of treatment has remained strong beyond six months from treatment initiation. Together, we believe this reflects both the positive impact of PYRUKYND on how patients feel and function and the strength of our commercial capabilities, including market access and patient services. In the first quarter of 2023, which represented the fourth full quarter of launch, we generated $5.6 million in net PYRUKYND revenue. A total of 127 patients have now completed a prescription enrollment form or PEF, including 22 in the fourth quarter of 2023. A 21% increase versus the fourth quarter of 2022. This has translated into net 89 patients on therapy, a 14% increase over last quarter. Patients on therapy continue to stem from a growing and diverse provider base of 113 physicians and represent a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population. I am confident that strengthening the commercial capabilities we are prioritizing today, including our ability to identify providers likely to treat patients appropriate for PYRUKYND, enhance diagnostic efficiency, activate a broad range of prescribers, and maintain long-term adherence and reimbursement, will help maximize the potential of the current launch and lay the foundation for potential launches in a meaningfully larger patient populations. Our next potential launch is in thalassemia, where approximately 60% of patients do not have an approved therapy in the U.S. Importantly, PYRUKYND has the potential to become the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across the full range of thalassemia patients, including both alpha-thalassemia and beta thalassemia. Alpha-thalassemia currently has no approved treatment options and will therefore require a particular focus on patient identification and disease education, leveraging the capabilities we're building in the current launch in PK deficiency. Beta thalassemia, on the other hand, is the more common form of the disease, constituting approximately two-thirds of the thalassemia cases in the U.S. Given its greater prevalence and more competitive landscape, we believe adoption in beta thalassemia will require a greater emphasis on market access and PYRUKYND's overall product profile, including efficacy, safety, and route of administration. Taken together, each of these potential launches will require a tailored commercial strategy, and we aim to leverage capabilities from our current launch to address the needs of each of these populations. The full range of thalassemia patients is comprised of approximately 18,000-23,000 patients in the U.S. and EU Five, and a meaningful addressable market outside these geographies, such as the Gulf Cooperation Council countries, or GCC, where the prevalence of thalassemia is eight to 9 x higher than the U.S. We look forward to evolving our commercial capabilities to meet the unique needs of our target diseases and deliver transformative new treatment options to these areas of profound unmet patient need. With that, I will now turn the call over to Cecilia. Thanks, Tsveta. Our first quarter 2023 financial results can be found in the press release we issued this morning, which I will summarize. More detail will be included in our 10-Q, which will be filed later today. First quarter 2023 net PYRUKYND revenue was $5.6 million, an increase of $1.3 million compared to Q4 2022. As PYRUKYND is the first therapy for this ultra-rare patient population, we continue to gather data and insights on the launch trajectory and will not be providing guidance at this time. Consistent with other rare disease launches, gross to net continues to be in the 10%-20% range. Cost of sales for the quarter was $0.6 million. Moving to expenses on the balance sheet. R&D expenses were $67.3 million for the first quarter, a decrease of $2.8 million compared to the first quarter of 2022. This decrease was primarily driven by the $1.5 million of reimbursable transition-related expenses we provided to Servier in the first quarter of 2022 related to the sale of the oncology business. SG&A expenses were $28.4 million for the first quarter, a decrease of $3.1 million compared to the first quarter of 2022 that was primarily driven by a reduction in workforce-related expenses. As a reminder, TIBSOVO royalty, which was recorded under royalty income from gain on sale of oncology business on our income statement, has ceased given the sale of our right to 5% royalties on U.S. net sales of TIBSOVO to Sagard for a one-time payment of $131.8 million in October 2022. As part of the divestiture of our oncology business to Servier, we retain rights to a potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales. We ended the quarter with cash equivalents, and marketable securities of approximately $1 billion. We expect our cash equivalents, and marketable securities, together with anticipated product revenue and interest income, will enable us to execute our operating plan, including funding the currently planned development programs for mitapivat, AG-946, and our PAH stabilizer, and commercialize mitapivat outside of the U.S. through one or more partnerships. To maintain our strong cash position, we will remain focused on proactively managing our cost base and deploying a disciplined cash allocation approach. I'll now turn the call back over to Brian for his closing remarks. Thanks, Cecilia. Given the rapid enrollment of our ongoing studies of PYRUKYND and thalassemia, the persistence of real-world PYRUKYND treatment in our current launch in PK deficiency, and our strong balance sheet, our team is energized and focused on advancing our industry-leading pipeline of PK activators to address the profound unmet needs of patients suffering from rare hematologic diseases. As we look ahead to the clinical and regulatory milestones we expect in the balance of the year, we will continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation. Finally, I'd like to thank all of our employees for their hard work and dedication to our mission of transforming the lives of patients living with rare diseases, and all of our partners, including the physicians, patients, caregivers, and participants in our clinical development programs. With that, we will now open the call for questions. 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. Please stand by while we compile the Q&A roster. Our first question comes from Gregory Renza with RBC Capital Markets. Your line is open. Great. Thanks, Brian and team. Congrats on the progress. Thank you for taking my question. Brian, maybe just more on the near term, if I may. I know there's little you and the team can perhaps say about the sickle cell readout that's upcoming. Perhaps if you could just remind us or provide some color around some of the scenarios that you are accounting for when it comes to factoring in your no-go decision. What is perhaps nested in there as you think about some of the potential outcomes of that data and how you think about the new information that's forthcoming? Also as it relates to Brian, just the consistency of the data. As you have mentioned, you've been very pleased with that over time and how that factors to the outcome as well. Thanks so much. Sure. Good morning, Greg, and thanks a lot for the question. You know, with respect to sickle cell disease, first off, I just wanna again commend Sarah and her team for the excellent progress that she's made, not just with sickle cell and getting us to the point of a data readout at the midpoint of the year. As we noted on the call, I'm especially proud of the fact that thalassemia now with screening completed, puts us in a position for a readout in that domain in 2024, and that's equally important as well. For sickle cell, we have, of course, a number of scenarios that we're planning for. We are hoping and planning for success, of course, and that's why the trial was designed to be operationally seamless, phase II, III. With success in the phase II readout, the great news there is that Sarah and the team would be ready to go quickly and leverage the same clinical site setup that we have in phase II. Obviously, this is a very high unmet patient need arena, we're eager on their behalf in that scenario to move forward. Specifically, with respect to what we're looking for for the data, and we've talked about this many times, that, we're gonna take a holistic approach as we look at the data. The primary endpoint, of course, in the phase II RISE UP readout will be focused on hemoglobin improvement. We have secondary endpoints, markers of hemolysis and the like. Of course, safety will be a key element, and that will also guide us on the dose that we would pursue with success. At a very high level, the way we're thinking about sickle cell disease is that we'll be looking for a hemoglobin plus dynamic. That could be hemoglobin plus a trend in VOCs, though it's a 12-week study, it's not designed for VOCs per se. It could also be patient feel and function. We know that having studied the sickle cell disease arena for quite some time, that is a very important dynamic. It's not just success for the patient in the short term, it's the ability to stay on a therapy chronically, which, by the way, is why we're so encouraged by the persistency that we're seeing so far in our PKD launch. Maybe I'll stop there and just see, Sarah, if you wanna add anything with respect to the scenarios. No, I think it's covered. I think we're very excited about the way the study is designed because it does allow and gives us flexibility for our different scenarios. I'll just say again, Greg, we're, you know, we're excited about the period to come. We have sickle cell disease readout at the midpoint of the year. We have thalassemia, where we're gonna be looking at the readout in 2024. We have AG-946, where we're looking for proof of concept in our phase II-A study in low-intermediate risk MDS at year-end. Earlier in our research pipeline, we have the PAH stabilizer that we're pursuing for IND at year-end. It's a pretty busy time to come, but thanks again for the question. Thanks, Brian. You bet. Our next question comes from Tess Romero from JPM. Your line is open. Good morning, guys. Thanks so much for taking the question. You've laid out a number of factors that will contribute to the go, no-go for mitapivat in sickle cell disease. Can you just remind us of the status of the phase I sickle cell disease cohort for AG-946? Do any of the results there in patients on AG-946 factor into this decision, right? In other words, could there be a scenario in which you elect to move AG-946 forward instead of mitapivat? Thanks so much. Thanks a lot, Tess. I'm gonna have Sarah weigh in on this one. Hi, Tess. For AG-946, the phase I is ongoing, and we have not disclosed the time points at which we will be presenting data. In regards to the second part of the question, AG-946 and mitapivat are at a totally different phase of development. You know, AG-348 has built, so mitapivat has built, you know, a huge safety profile, has much longer exposure and is really, you know, past the phase I development. To substitute the one compound for the other is not something that we believe is doable just in the context of each product needs to build up its own safety profile. AG-946, in our view is less advanced at this point. Tess, I'll again just reiterate that, and I started the call this way, that with Agios as the leader in PKR activators, we are pleased to have not one, but two that we're pursuing in clinical trials. That gives us, as you noted, quite a lot of optionality. The near term readout that we're quite eager to see would be in the low intermediate risk MDS patient population again at the year-end. It is quite an advantage to even be able to stratify across different therapeutic areas with two PKR activators when we get into the data readout, if positive, preparing for launch and then the economics that could surround that to have two is particularly advantageous versus having all therapies lined up within one. Thanks again for the question. Thank you. Thank you. Our next question is coming from Mark Breidenbach from Oppenheimer. Your line is open. Hey, good morning, guys. Thanks for taking the questions. Two quick ones from me. First, with respect to the ENERGIZE and ENERGIZE-T trials, which are nearly completing enrollment, I'm curious if you've seen any trends in specific geographies that are enrolling patients fastest, given that these trials have so many ex-US clinical sites, and is that trend potentially gonna influence your plans for regulatory filings, which territories to file in first? The second question is just with respect to vorasidenib and the maybe Servier's plans for a future NDA filing. Do you have any clarity on when such a filing might happen? Thanks for taking the questions. Sure. Thanks a lot, Mark. We'll take those in sequence. Sarah, you wanna start off with ENERGIZE-T and the clinical trial geographies? Sure. We've presented in the past our clinical trial distribution globally. This is really in the context of reflecting where thalassemia is present and also reflecting how the distribution of thalassemia is between different genotypes because the program is developed to deliver a product for all thalassemia, meaning alpha and beta thalassemia regularly and non-regularly transfused. The clinical development program is designed that way, but also designed in such a way that it is feasible to enroll these trials that way. So far we have been very pleased with how that has worked out. Our clinical trial enrollment is really reflective of the distribution of thalassemia globally, and so we do not see any changes needed to any of our regulatory strategy to date. I'll just add before we transition to Cecilia for the question vorasidenib that, you know, having Tsveta Milanova on board as our Chief Commercial Officer is really advantageous, Mark, when we think about with successful data, to your point, your question about launch sequencing. As Sveta spoke about in her remarks, thalassemia is a uniquely concentrated addressable market geographically. We will be particularly thoughtful about the sequencing in part, well, of course, to address access for the most patients in those geographies as possible, but also with an eye towards the value maximizing economics with respect to pricing and so on. Again, this all comes obviously with positive data, but it puts us in a position of strength with respect to how concentrated that population is. Having Tsveta on board as a world-class expert in globalization of rare disease products is a real advantage. Maybe we'll have Cecilia comment on vorasidenib. Yes. We're very excited obviously to hear the phase III results. It's a great for huge unmet need for patients. From our side, we retain the rights for a $200 million milestone on FDA approval and the $15 million, sorry, 15% royalty on net U.S. sales. We don't have clarity on timing yet. We'll provide an update when we have it. Obviously this is in Servier's shop, but the original science and progress came out of Agios, so I know we've got a lot of Agios employees listening in as well. I just wanna say we are off the charts proud of what that could mean for glioma patients where they haven't had any progress in the last 20-plus years. This only adds to the track record that Agios has had across a number of fronts, and now we're leveraging all that great science into our progress in PKR activation. Thanks so much. You bet. Okay, one moment. We have a question from Greg Harrison with Bank of America. Your line is open. Hey, good morning. Thanks for taking the question. How would you say your PAH stabilizer is different from a drug like Kuvan? Where would you see it fitting in the PKU treatment landscape with enzyme replacement and gene therapy approved or under development? Greg, first off, good morning. I will start by saying too early to give too much on that front. We are keen to progress our PAH stabilizer to IND, but I'm gonna let Sarah comment further. I think our program is really designed, like all of our programs, are really designed to target unmet need in patient populations. For this one specifically as well, we will be designing the program to meet a product profile that we believe is, can provide meaningful difference for patients living with PKU. The current therapies available each have their limitations. That is what we are hoping to address with this product, to create a differentiation there. That can be on the safety profile, but also on the amount of product people need to take, to get to some meaningful difference and to actually also shoot for further reduction of a better improvement basically of the phenylketonuria overall. More to come on that as we progress the molecule. Of course, it's early now, and as with any phase, moving to IND and then phase I, we will be learning as we develop the program. It's another great example of why we're so passionate about rare diseases, because every single therapeutic area that we pursue is desperate for innovation and disruption and, you know, whether that's PKD or sickle cells we've talked about already, thalassemia, MDS and PAH, that's the common thread of our focus. Got it. That's helpful. If I could sneak one quick one in on- Sure. On the sickle cell. What forum will you use to announce that data? Would it be a press release or a conference? Will you be announcing the go/no-go decision at the same time, or could there be a delay? In regards to how and when we will announce, it will depend on when we receive the data, but we are planning to do a press release which will not include all of the data because of course we do want to present at a medical meeting. It's always a balancing act between those two. In typical Agios fashion, I think what we've done for our past programs like PKD, you can expect something in that similar vein. Yeah. I mean, our target will be to give our stakeholders enough clarity as to the why behind our decision, whichever way that goes based on the data. Got it. Thanks again. You bet, Greg. Thanks. Thank you. One moment. We have a question from Divya Rao from TD Cowen. Y our line is open. Hi, guys. Thanks for taking our questions. This is Divya on for Mark. Given the commentary on needing to see this hemoglobin plus response, if the VOC trend isn't the view or isn't seen, is the view that the PRO analysis would be predictive of ultimately showing a VOC benefit, or do you think the PROs themselves support this hemoglobin plus commercial profile? I guess specifically, are there any PROs that are particularly important? This is the phase II readout, right? The PRO analysis and VOC benefit, all of that will really come at the end of phase III in line with our product profile. What we are doing now with the phase II, it has primary endpoints of hemoglobin response and safety, and then indeed secondary endpoints that encapture, you know, PROs, VOCs, hemolytic parameters. Those we will be looking for trends in those datasets. We will of course, be looking at the totality of the data generated to date across the different studies that are using mitapivat in sickle cell disease, and that is being taken into account. That's helpful. If I could sneak another one also. On PKD, I guess one, was there any stocking effect seen in Q1? With this being the second month of reauthorizations, are you seeing any trends or I guess changes in the way payers are evaluating what would be considered a response or benefit? Thanks, Divya. I'm gonna have Cecilia comment on stocking. Sveta is always eager to talk about launch dynamics. Cecilia. Thanks, Brad. As a reminder, we have a limited distribution model. We have one specialty pharmacy and one specialty distributor. Our inventories on hand are limited. You see there might be some fluctuations quarter-to-quarter. We're still talking about small numbers. Nothing meaningful. Yeah. Tsveta? Absolutely. As I noted also in my remarks, we are really encouraged with the positive reception of PYRUKYND's profile from patients, physicians, and on the payer front as well. When it comes to treatment initiations, but also we see that reauthorizations as well. Until today, the reauthorizations have not been a barrier. Patients do utilize the inclusion/exclusion criteria as well as the primary endpoint defining in the clinical trial to assess reauthorizations. However, the totality of the product profile is taken into account, and we see that both in the success of the reauthorizations and the strong persistency, we see, even though early in the launch with small patient numbers, so patients will continue post six months of reauthorization as well. We hope that, you know, on today's discussion, we hope that message really comes through that PYRUKYND in PKD is performing, and we certainly have heard that anecdotally from patients. We now are starting to see that in persistency. Our market research, as Sveta had commented on earlier, has certainly indicated that the clinicians who are on our target list, which is inclusive of those who have actually prescribed PYRUKYND, share in that enthusiasm. The launch dynamic really is not so much around access or enthusiasm for the product. It's really about education, diagnostic efficiency, and activating patients especially to begin therapy. That's really the where Sveta's emphasis commercially is focused. That's helpful. Thank you. You're welcome. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Hi. Good morning. This is Anu Midha for Salveen. Just one on the PKD launch. Could you just provide an update on patient discontinuation rates and whether what you're seeing in the real world is consistent with what was observed in the clinical trials? Then just on sickle cell, I guess you've walked us through what you're going to be looking at in terms of the data, but I guess, are there specific deal breakers from the factor that you're looking at that would lead to a no-go decision? If you could just, you know, frame that scenario. Thank you. Sure. We'll do that again in sequence. Sveta can start with PKD discontinuations and then Sarah on sickle cell. Absolutely. As we mentioned, we are really encouraged to see that the efficacy of PYRUKYND, which we observed in the clinical trials and experience there, is very much translating into persistency to therapy in the real-world setting. With that in mind, discontinuations have remained lower overall and so far. As we mentioned, reauthorizations have not been a barrier, and adherence for the product remains strong. This is very much reflective, I think, of the PYRUKYND value proposition in PKD, but it really gives us also the encouragement that the importance of persistency, which is associated with PYRUKYND, could potentially translate in other indications, future indications we are looking to expand into. That can be a critical differentiator, knowing how important persistency and adherence in other diseases can be. Super. Sarah? Yeah, I think to that point of the clinical trial, that persistency and adherence we've seen in the clinical trials, which has allowed us to continue to follow patients in the long-term extensions, which has allowed us to continue to study, you know, maintenance of effect, impact on how patients feel and function. We're also very excited about our iron overload data that we continue to present. It's that compelling data across the board, as Sveta mentioned, it's very important to us, because we also look at that in the context of the other hemolytic anemias. Turning to the other hemolytic anemia, sickle cell disease. In regards to the no-go scenarios there are some obvious, no-go scenarios as what would be on the clinical trial, as expected for a clinical trial, is when a clinical trial would fail. If you do not see hemoglobin response, for instance, in the primary endpoint, or we have a safety signal that tips the benefit to risk profile the wrong way, things like that are all proactively defined in our go, no-go scenarios. We have as for any other clinical development program, clear goals and then scenarios in which more data will need to be assessed. Thank you. Thank you. Thank you. I'm showing no other questions in the queue. I'd like to turn the call back to Mr. Brian Goff for any closing remarks. Thanks a lot, thanks everyone for participating in today's call and of course for your continued interest in Agios. As you heard this morning, we are making great progress across our portfolio. I am incredibly proud of the team for what they're doing on behalf of patients who count on us, I'm confident in our potential to continue to deliver significant value for both patients and our shareholders. Thanks a lot, we look forward to speaking with you soon. This concludes today's conference call. Thank you for participating. You may now disconnect.