Good morning, welcome to the Agios Second Quarter 2023 conference call. At this time, all participants are on 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 Chris Taylor, Vice President, Investor Relations and Corporate Communications for Agios. Thank you, operator. Good morning, everyone, and welcome to Agios Second Quarter 2023 conference call. You can access slides for today's call by going to the investors section of our website, Agios.com. On today's call, I am joined by our Chief Executive Officer, Brian Goff; Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development; Tsveta Milanova, our Chief Commercial Officer; and Cecilia Jones, Chief Financial 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 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'll turn the call over to Brian. Thanks, Chris. Good morning, everyone, and thank you for joining us. Agios is focused on delivering transformative therapies for patients living with rare diseases, and in particular, we're the pioneering leader in PK activation focused on hematologic diseases. In the second quarter, we made significant progress advancing our industry-leading pipeline of PK activators targeting hematologic diseases that share a common underlying pathophysiology. With each step forward, each data readout, the probability of success for the platform is strengthened, and we are excited to share our updates with you today. As we articulated at the beginning of this year, we're prioritizing potential business development opportunities based on five key criteria: rare disease focus, transformative for patients, an identified regulatory pathway, potential to de-risk early, and a clear path to value creation. Earlier this morning, we were very pleased to announce a license agreement with Alnylam Pharmaceuticals, the leading RNAi therapeutics company that is highly aligned with these five criteria. Under this agreement, Agios will acquire the rights to develop and commercialize Alnylam's novel preclinical siRNA for the potential treatment of polycythemia vera or PV. PV is a rare and potentially fatal hematologic disease that affects approximately 100,000 patients in the U.S., and for which phlebotomy is the standard of care. Our goal is to address the high unmet need in PV by delivering a convenient, disease-modifying treatment option that reduces or eliminates the need for phlebotomy. This agreement is therefore aligned not only with our business development strategy, but also our core scientific expertise and clinical and commercial capabilities in rare hematology. We look forward to initiating IND-enabling studies later this year. Sarah will provide more detail on the siRNA development candidate in just a few minutes. The study met the primary endpoint of hemoglobin response for patients in both mitapivat treatment arms, and in recent weeks, our team has continued to analyze the results and has selected the 100-milligram dose for the phase III portion of the study. We are now focused on phase III execution and are quite eager to enroll the first patient later this year. Broadly, these results add to the growing body of consistent and compelling data that we have continued to generate with our PK activators, highlighting the potential of this differentiated mechanism of action to transform patient function, quality of life, and long-term outcomes across multiple disease areas. In fact, with more than 8 years of clinical experience and the largest data set for any PK activator, PYRUKYND has demonstrated consistent results across three distinct diseases. In this context, we were also pleased to announce this quarter that we've completed enrollment in both phase III studies of mitapivat in thalassemia, as well as the phase IIa study of our novel PK activator, AG-946, in lower-risk MDS. This progress reflects our operational excellence in clinical development and investigators' enthusiasm for the potential of PK activation in these indications. Based on this progress, we continue to expect two readouts from the ENERGIZE and ENERGIZE-T phase III studies in thalassemia next year, and we've pulled forward the expected timing of the top-line results for the phase IIa study in lower risk MDS to the end of this year. Turning to our commercial business, we're encouraged to see that the consistent and compelling efficacy of mitapivat observed in the clinical trial experience has continued to translate to persistency on therapy among adults living with PK deficiency in the real world. As we continue to maximize the opportunity in the current launch in PK deficiency, we're building the capabilities needed to fully realize the potential of anticipated future launches in 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 second quarter with a cash position of nearly $950 million on the balance sheet. One brief reminder, as part of the divestiture of our oncology business to Servier in 2021, we retained the rights to a potential $200 million milestone upon FDA approval of vorasidenib and royalties on potential U.S. net sales. We were encouraged by the results of Servier's phase III trial, and we look forward to tracking next steps. We're expecting a number of additional milestones by the end of the year, including enrolling more than half of the patients in the phase III ACTIVATE-Kids and ACTIVATE-KidsT studies of mitapivat in pediatric PK deficiency, filing the IND for our PAH stabilizer for the treatment of PKU, and the newly added milestone, the data readout from the phase IIa study of AG-946 in lower risk MDS. We're very enthusiastic about the clinical development momentum we're building and look forward to anticipated readouts from the phase III studies of mitapivat and thalassemia in 2024, and readouts from the phase III studies of mitapivat in sickle cell disease and pediatric PK deficiency in 2025. With that, I'll now turn the call over to Sarah. Thanks, Brian. Sickle cell disease is a serious, potentially fatal hematologic disease that affects approximately 120,000-135,000 patients in the U.S. and EU5. Today, there are no novel oral treatment options that both improve anemia and reduce sickle cell pain crises, that is what we aim to deliver for these patients. Turning to the top-line data of the RISE-UP phase II study, treatment with mitapivat demonstrated a statistically significant increase in hemoglobin response rate compared to placebo. Hemoglobin response was defined as an increase of one gram per deciliter or more in average hemoglobin concentrations from week 10 through week 12, compared with baseline. 46.2% of patients in the 50 milligram BID mitapivat arm and 50% of patients in the 100 milligram BID mitapivat arm achieved a hemoglobin response, compared to 3.7% of patients in the placebo arm. These increases in hemoglobin response were accompanied by improvements in markers of hemolysis and erythropoiesis, as well as numerical reductions in the analyzed rate of sickle cell pain crisis for this 12-week study. Specifically, patients in the placebo arm experienced an analyzed rate of sickle cell pain crisis of 1.71, compared to 0.83 in the 50 milligram arm and 0.51 in the 100 milligram treatment arm. The safety profile for mitapivat observed in the study was generally consistent with previously reported data for mitapivat in other studies of sickle cell disease and other hemolytic anemia. There were no adverse events leading to discontinuation in any study arm. Finally, of the 79 patients enrolled in the study, 73 continued in the phase II open label extension period. These data further underscore the potential of mitapivat to address the high unmet need of patients with sickle cell disease by delivering a novel oral treatment option that both improves anemia and reduces sickle cell pain crisis. We are excited to present a full analysis of the phase II data and have submitted an abstract for ASH later this year. Based on continued analysis of the compelling data observed at both doses in recent weeks, we have selected the 100 milligram dose for phase III. As a reminder, the phase III portion of RISE UP will include a 52-week placebo-controlled period in which 198 patients will be randomized two to one to either mitapivat or placebo twice daily. The primary endpoints are hemoglobin response and analyzed rate of sickle cell pain crisis, and we look forward to enrolling the first patients in the phase III portion of the RISE UP study in the fourth quarter of this year. Turning to our broader development pipeline, we have been very pleased with the pace of enrollment across our programs in the first half of the year. We have completed enrollment in both phase III studies of mitapivat and thalassemia, including ENERGIZE, which enrolled patients who are not regularly transfused with a primary endpoint of hemoglobin response, and ENERGIZE-T, which enrolled patients who are regularly transfused with a primary endpoint of transfusion reduction response. Together, these studies will deliver data relevant to the entire thalassemia population and thus allow us to evaluate the potential of mitapivat to become the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across all thalassemia subtypes. We look forward to the readout of the ENERGIZE study in the first half of next year and the readout of ENERGIZE-T in the second half of next year. We were also pleased to complete enrollment in the phase IIa study of AG-946 in lower-risk MDS this quarter, several months ahead of schedule. AG-946 is a novel PK activator that has the potential to strengthen our PK activator franchise. We now expect top-line results from the phase IIa study of AG-946 in lower risk MDS by the end of this year, making this our next clinical data readout. As a brief reminder, the primary objective of this study is to establish proof of concept for AG-946 in participants with lower risk MDS by measuring the following primary endpoints: hemoglobin response, defined as an increase of 1.5 grams per deciliter or more from baseline in the average hemoglobin concentration from week eight through week 16, and transfusion independence, defined as transfusion-free for eight or more consecutive weeks during the study for participants with low transfusion burden only. In parallel, we continue to advance the phase III ACTIVATE-Kids and ACTIVATE-KidsT studies of mitapivat in pediatric PK deficiency, and progress towards the filing of the IND for our small molecule PAH stabilizer to directly address the underlying cause of phenylketonuria or PKU. Finally, as Brian mentioned, we are pleased with the agreement that we announced this morning together with Alnylam, a pioneer in RNAi therapeutics with a best-in-class platform. Polycythemia vera is a rare hematologic disease that is well-aligned with our internal expertise. PV is characterized by excessive production of red blood cells, which leads to increased blood volume and viscosity and can result in thrombosis, cardiovascular events, and death. The siRNA development candidate targets TMPRSS6, a key driver of red blood cell production. Knockdown of TMPRSS6 increases hepcidin and reduces red blood cell production. We look forward to initiating IND-enabling studies later this year and leveraging our deep expertise in rare hematology as we progress this program towards the clinic. With that, I will now turn the call over to Tsveta. Thank you, Sarah. Our commercial organization remains focused on maximizing the opportunity in the current launch in PK deficiency by executing on our strategy across all phases of the patient journey. The capabilities we're building today on disease awareness and education, access and initiation, and adherence and persistency, will also serve as a foundation to fully realize the potential of anticipated future launches in thalassemia, sickle cell disease, and low-risk MDS. Our market research data continue to 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 level, reduction in transfusion frequency, and a positive impact on long-term disease complications. To better understand the treatment experience on PYRUKYND, we recently conducted interviews with a sample of patients or their caregivers. Most patients reported positive experiences, including improvement in hemoglobin and in energy levels, reduction in fatigue, and decreased transfusion burden. Importantly, this feedback from both patients and clinicians is consistent with the strong persistency of treatment use we observed in the real world after the initial payer reauthorization. Moreover, discontinuations remain low and reauthorizations have not been a barrier. In the second quarter of 2023, we generated $6.7 million in net PYRUKYND revenue, a 20% increase over Q1 this year. A total of 147 patients have now completed a prescription enrollment form or PES, including 20 in the second quarter of 2023, a 16% increase versus the first quarter of 2023. This has translated into net 99 patients on therapy, an 11% increase over last quarter. Patients on therapy continue to stem from a growing and diverse provider base of 130 physicians and represent a broad demographic and disease manifestation range that is consistent with adult PKD deficiency population. Given the ultra-rare nature of this disease, we continue to expect slow and steady uptake. In these early stages, we remain focused on identifying providers likely to treat adult patients with PK deficiency. Our efforts center on utilizing data and analytics to improve physician targeting, as we believe there are a meaningful number of potential prescribers who may have adult PKD patients under management. We also continue to improve efficiency and impact, educating treating physicians, and instilling a sense of urgency regarding the benefits of diagnosis and appropriate treatment. By doing so, we'll help to maximize the potential of the current launch and lay the foundation for potential launches in meaningfully larger patient populations. The first of these potential launches is in 2025 in thalassemia, where approximately 60% of thalassemia patients in the U.S. do not have an approved treatment option. This next slide illustrates the breakdown of thalassemia subtypes in the U.S., including alpha and beta thalassemia, and transfusion-dependent and non-transfusion-dependent thalassemia.... Importantly, mitapivat has the potential to become the first oral therapy to improve hemolytic anemia and ineffective erythropoiesis across the full range of thalassemia patients. Given the relative prevalence and competitive differences across thalassemia subtypes, we look forward to implementing a fit-for-purpose commercial strategy that leverages capabilities gained from the current launch. Together, the full range of thalassemia patients is comprised of approximately 18,000-23,000 patients in the U.S. and EU5, and a meaningful addressable market in additional geographies such as the Gulf Council countries or GCC, where the prevalence is approximately 70,000 patients. The prevalence of sickle cell disease is also concentrated in the U.S. and GCC region. This overlap in select geographies provides an opportunity for us to leverage our commercial efforts in thalassemia to accelerate and support the future launch in sickle cell disease. With that, I'll now turn the call over to Cecilia. Thanks, Tsveta. Our second quarter 2023 financial results can be found in the press release we issued this morning, more detail will be included in our Form 10-Q, which will be filed later today. I'd like to take a moment to provide some context and highlight a few points. Second quarter 2023 net PYRUKYND revenue was $6.7 million, an increase of $1.1 million compared to Q1 2023. As PYRUKYND is the first therapy for this ultra-rare adult PKD patient population, we continue to gather data and insights on the launch trajectory and will therefore not be providing guidance at this time. We continue to expect a slow and steady trajectory to peak. Consistent with other rare disease launches, growth to net is expected to be in the 10%-20% range on an annual basis. Cost of sales for the quarter was $1.1 million. Moving to expenses and the balance sheet. R&D expenses were $68.9 million for the second quarter, a decrease of $5.6 million compared to the second quarter of 2022. This decrease was primarily driven by a decrease in workforce-related expenses as a result of reduced headcount related to the evolution of our research organization in 2022. SG&A expenses were $30.4 million for the second quarter, an increase of $2.1 million compared to the second quarter of 2022. That was primarily driven by an increase in stock-based compensation expense. As a reminder, Tyvaso royalty has ceased, given the sale of a right to 5% royalties on U.S. net sales of Tyvaso to Sagard 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, cash equivalents, and marketable securities of approximately $947 million. We expect that this pattern, together with anticipated product revenue, interest income, and the potential vorasidenib milestone, will enable the company to fund our operating expenses and capital expenditures through several value-creating milestones and at least into 2026. This guidance does not include cash inflows from potential royalties from vorasidenib, commercializing mitapivat outside of the U.S. through one or more partnerships, or other potential strategic business or financial agreements. We are excited about our potential near-term PYRUKYND launches and continue to expect peak sales of $200 million-$225 million for PKD in the U.S. and $1 billion for worldwide revenues for PKD and thalassemia combined. We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined cash allocation approach as we prepare to support the potential additional launches of PYRUKYND and continue to make strategic investments to advance and grow our pipeline, all of which impacts our timing to profitability. Following the significant momentum created through the execution of our development plans and as we approach additional upcoming potential value-creating milestones on the horizon, I am confident that our strong balance sheet will enable us to execute from a position of strength to continue to look for ways to create shareholder value. I will now turn the call back over to Brian for his closing remarks. Thanks, Cecilia. This was a tremendous quarter at Agios. We announced positive phase II data in sickle cell disease, completed enrollment in 3 clinical studies, in-licensed a compelling external program that has the potential to transform the course of a rare hematologic disease with profound unmet need, and we continue to strengthen our commercial capabilities to support future launches. The data we continue to generate across our industry-leading pipeline of PK activators remain consistent and compelling, and we continue to make meaningful progress towards our vision for Agios, which is to develop an established hematology franchise with approvals spanning 3 hemolytic anemias and an expanded portfolio fueled by business development and advancement of our internal pipeline that is aligned with our core expertise in rare disease. As always, we'll 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'll open the call for questions. 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. We'll compile the Q&A roster. One moment for our first question. Our first question will come from the line of Greg Harrison from Bank of America. Your line is open. Hey, good morning. Thanks for taking the question, and, and congrats on all the updates. To start off, curious what factors led you to the decision to license the PV treatment from Alnylam? Is this a model for future BD in terms of development stage, and having the potential where you could add your own expertise and value? Would you expect this asset to be broadly applicable across PV patients, or, or would it be more focused on a specific patient population? Sure. Well, good morning, Greg, thanks a lot for the question. Yes, it's been a great quarter, I'm happy to provide some comments around the deal that we announced this morning. This is, polycythemia vera is a large market. We believe it is ripe for disruption and growth. As I noted in my comments, you know, if you just think about the standard of care, it's phlebotomy. To us, that's just a great opportunity to do what we do best, which is reinvent the way that these rare diseases are treated and bring potential disease-modifying therapies to these patients. We're really excited about this particular TMPRSS6 asset from Alnylam. It fits really well with our disciplined BD criteria, builds on our core capabilities, that's across our scientific expertise, our development capabilities, our commercial capabilities. If you think about the BD criteria that we've talked about so many times, it checks all the boxes. This is a rare disease. It is transformational potential for patients. We see an opportunity for early de-risking, which we've talked about a lot as a sweet spot for us. We believe there's a clear regulatory pathway, and ultimately, this will be value-creating, is our strong belief. It comes from the Alnylam, you know, world-class RNAi platform, we also have strong conviction in the probability of success from the data generated to date. We're excited about this. I guess, to your question of where we go from here for clinical development, I think, and I'll, I'll ask Sarah if she wants to make comments, but it's a little too early for us to define the target product profile specifically. We have many options. We'll be looking at efficacy dimensions, speed of action, for the product itself for patients, safety profile, and of course, convenience. All of those are in play, but given the stage of development, we're just gonna pause and bring the asset in, really look at it deeply for where, where we can put our development expertise in motion, and then we'll provide updates accordingly. The last thing I'll just say to your point about, is this a theme of the types of BD deals and so forth going forward? We retain optionality for a range of different BD deals. This one, in particular, really, as I mentioned, checked all the boxes, and so we were eager to bring it in, but we'll, we'll retain our disciplined BD criteria going forward. Sarah, anything you wanted to add? Only to say that, you know, we're very excited about this. We are, of course, once we move forward with the program and have more details on our clinical development program, we will always be shooting to deliver value for patients and make a meaningful change with the development program, and you can expect execution on the program as well. We are excited to do that. Thanks, Greg. Great. That's helpful. Thanks. One moment for our next question. Our next question will come from the line of Gregory Renza from RBC Capital Markets. Your line is open. Great. Good morning, Brian and team. Congrats on the progress, and thanks for taking my questions. Sure. Maybe just a couple quick ones from me. Just following up on the in-license Alnylam asset, maybe it'd be helpful just to hear your thoughts and Sarah's, just on the preclinical data to date. Certainly, others exploring manipulation of TMPRSS6, and just curious, like, how you think this asset can potentially differentiate or sets up well when you survey the available data to date. Secondly, great to see the dose selection for the phase III and Sickle. Just curious, the rationale as you looked at the body of data over the last several weeks since the top line and made the step for the 100 mg. Thanks so much, congrats again. Hey, thanks a lot, Greg, and I'm going to send this over to Sarah then for both questions. Yeah, thank you. Around the preclinical data, you know, it has demonstrated in vivo proof of concept in non-human primates, with a safety profile that was very favorable and very good knockdown of the target observed. We feel very confident about that. As we mentioned earlier, we're very eager to get going on the IND-enabling studies and the CDP and provide more detail as on that as we, you know, progress with that. I think for us, yes, there are others that are also looking at this target. To Brian's point, this is a very big market. There is going to be differentiation around efficacy, safety, mode of administration, and also frequency of administration. We believe that our CDP will be able to deliver on what the market needs. Yes, again, very excited to get going on this. For your second question around the phase III dose selection for sickle cell disease, obviously, we are very excited. We're, we're very excited about the data of the phase II, and we're very fortunate to have both doses show benefit-risk profile that was favorable. We have pre-specified criteria in the protocol, the team had time to now look at all of the data, we, we followed that framework and selected the 100 milligrams. We have not disclosed further details on the data. You know, we mentioned that we have submitted the abstract to ASH, and so are now awaiting the outcome of that, and then we're hopeful to be able to provide all that detail at that conference. Greg, maybe I'll just tag on too, and say I always love to take the opportunity to speak with pride about Sarah and her entire R&D team. This is just a great example of the excellence operationally that we have and the efficiency of the design of the RISE UP phase II/III trial, and the fact that we were prepared for both doses. We were thrilled to see that both doses were effective, and now that we have the 100-milligram dose, the fact that we can proceed in the 4th quarter with the 1st patient dose in the phase III trial, I think is, you know, again, just a mark of excellence and a real point of pride for the organization. Absolutely. Thanks, Brian, and thank you, Sarah. You bet. Thanks a lot. One moment for our next question. Our next question comes from the line of Divya Rao from Cowen. Your line is open. Hi, everyone. Thanks for taking our question, and congrats on the quarter. This is Divya from Cowen. Just two from us. We're just curious, what do you define or how do you define success in the MDS trial? I know that there are other, you know, several mechanisms that are being touched in this space. Do you view those as competitive, or do you see those more as opportunities maybe to build combinations with AG-946? Then I have a follow-up. Yeah. Thanks, Divya. I will just start by saying, as is the case with, all the disease areas that we're focused on, we have a very different mechanism of action with pyruvate kinase activation. And of course, you know, the question for low-risk MDS, this is with our other PK activator, AG-946, and I know Sarah will be eager to talk about what we're awaiting in terms of the phase IIa data. Yeah, thanks for the question. I think for the MDS program, one, I want to highlight here again that the team has done an amazing job on enrollment of that phase IIa program. I think it also highlights the enthusiasm of the investigators for this mechanism of action for MDS patients. We are, we have not declared our framework for MDS to define success, but it is a phase IIa, we are indeed looking for a signal of efficacy and favorable safety. Our setup, if that's, if that's there, then we are set up to move fast into a phase IIb, in which we will do a proper dose finding. It is indeed a market that is evolving, and it's, I think it speaks to that this is also a market that is ripe for a change. We do believe that with this very differentiated mechanism of action, which is not being currently studied by or not as far advanced by others, that we really are set up for success there as well. I think what cannot be underestimated, is that ours is also an oral therapy, which provides the convenience of use for a patient population that is typically an older patient population. That, that's really helpful. Just a quick question on the sickle cell program. Could you remind us on if you've disclosed the powering assumption for the phase III trial? Have you discussed the 100-milligram dose with the FDA, or is that just mostly based on your internal discussion, and analysis of the data? For the sickle cell disease program, the 100 milligram dose, right now this is the internal framework that we have applied and all of the data that we have assessed. We are very excited about the end of phase II meeting with the FDA. We always look forward to our, the constructive dialogue that we have together. You know, it's, it's always, it's always great because I do feel like we are all wanting the same thing, right? For across all of our programs, we are really shooting to deliver medications that have a favorable benefit risk and can provide change to patients. We're always very pleased with the constructive dialogue that we have. In regards to the powering assumptions, obviously the phase III is much bigger sample size than the, than the phase II. We, there's two endpoints there. For the primary endpoint, the hemoglobin endpoint, we use and leverage our internal data for all of the statistical underpinnings. Then for the VOCs, obviously, we have been looking at other programs to make powering assumptions there and are looking to make a meaningful change on VOCs for patients. Thank you. One moment for our next question. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is open. Good morning. This is Anu Midha for Salveen. Just one question from us on the licensing agreement with Alnylam. Given the novelty of the siRNA modality for Agios, what gives you confidence in the clinical development process? Thank you. Thanks for the question. I think it gives us confidence because we do have internal expertise that have worked on this modality, but also on many other modalities. It's not like, while this is a new compound or modality for Agios, it's not a new compound for Agios employees. And so we're looking forward to putting that internal knowledge to work. And I do think in the context of endpoint, patient populations, all of that, it's straight into our wheelhouse of hematology drug development, and so we are looking forward to putting those skills to work there as well. Thank you. One moment for our next question. Our next question comes from the line of Andy Berens from Leerink. Your line is open. Hi, thanks. congrats on the deal. My questions are also on the MDS program. I was wondering if you could give us some overview of how you see the PKR class in MDS. I think luspatercept is, is actually doing pretty well on that indication, with sales over $700 million in a subpopulation. Can you give us the physiological rationale for the PKR class in MDS, as well as how you see it potentially being used relative to the EPO agents? lastly, I know it's early, but how do you think the usage of EPO agents in that disease hypothetically impacts pricing power? Yep. Andy, thanks a lot for the question. I'll just start by reinforcing what you just said. We find it a very attractive opportunity based on the current incumbents and the progress that they're making. The patient population, as we had on one of our slides, you know, we identify as 75,000-80,000 patients across the U.S. and EU5. It is another disease that is ripe for disruption and coming in with PK activation, a very different mechanism of action. As Sarah has noted a couple of times already, on top of all that, as an oral small molecule, we think has significant potential to be differentiated, but of course, we're going to be guided by the 2A data. You want to comment further, Sarah? Well, just on the part of the rationale why we believe PK activation may work in MDS, it's truly, there are similarities between MDS and thalassemia, that, and we obviously have now progressed in thalassemia quite well. That is one piece. It also, the glycolytic pathway is impacted in MDS patients at multiple levels, which we believe we can influence as well. There is hexokinase to pyruvate kinase ratio disruptions. There is also a fact that MDS patients often have an acquired PK deficiency. There's a multitude of reasons why we believe PK activation may provide benefit. We have published data on this at EHA, at ASH, and hopefully more to come at ASH. We are very excited about, you know, the evidence that we continue to build in this disease. Andy, just one other comment I'll add is, our team goes deep across many potential therapeutic areas that we're focused on and, you know, sitting with us today, we have Tsveta Milanova, our Chief Commercial Officer, who actually has been very involved in this space, so it's early, of course, we're, we're looking at phase IIa data. Beyond that, Tsveta will be able to add a lot of insight and expertise in not just the commercial profile of the product, but also, as you asked about, you know, pricing down the line and how we maximize the value creation. We feel like we're really well prepared and cannot wait for this upcoming milestone by year-end. Great. Thanks very much. You bet. Thank you. One moment for our next question. Our next question comes from Tess Romero of JP Morgan. Your line is open. Hi, Brian and team, good morning. Thank you for taking our question. I thought I'd ask a commercial one today. For PYRUKYND, as you grow patients on drug, just trying to get a sense of how you think about trajectory of new patient adds here. It sounds like the drop-off is pretty low. Do you think this run rate of 10 or so sequential net patients adds, like you've seen in the last couple of quarters, is the right way to think about the launch going forward, versus something maybe more accelerated given some of the initiatives on analytics, et cetera? Thanks so much. Yeah, thanks. Thanks, Tess. Tsveta is thrilled to have a question about commercial, so I'm gonna let her comment. Hi, Tess. Good morning. As you said, we continue to make progress on the launch. Most importantly, we continue to see the strength of the PYRUKYND's profile in the real world, especially when it comes to persistency, the positive provider feedback, and the payer support. At the same time, we also know that PKD is an ultra-rare disease, and as we said, through our opening remarks, we would expect to continue to see slow and steady uptake. We expect to see some variability, quarter over quarter, our efforts continue to be laser-focused on identifying the right providers, providers who are likely to have patients with PKD deficiency and patients who are appropriate for PYRUKYND, either today or potentially in the future. This is where our efforts in data and analytics continue, to support our team, as we continue to execute in the field. Very importantly, all the capabilities we're building today serve as a very good foundation for us as we continue to look into the future and potential future indications, and expansions for PYRUKYND such as thalassemia as well. Yeah, I, I mean, the only thing I'll just add, Tess, is that this is a very unique kind of launch. It's pretty far on the ultra-rare spectrum, and we're building learnings from it, but I, I would look at it as slow and steady growth, and we always caution to just be a little bit careful over quarter-over-quarter because it'll be lumpy for quite some time. We are very proud of the progress that Tsveta and the team continue to make. Great. If I can just squeeze in a commercial follow-up there. You know, given these dynamics, how do you think about providing longer-term PYRUKYND guidance? Is that something you feel like you may be in a position to do as we kind of exit 2023 and get into next year? Sure. Thanks. Cecilia, you want to take it? Yeah, I can take that. As, you know, as we mentioned before, this is a for a ultra-rare first therapy. We continue to learn data and insights. At this point, we're not gonna give guidance. There will come a point. We'll continue to evaluate when it's the right time to do that. Yeah, we... Our anchor point, as we've talked about, peak sales, $200 million-$225 million in the U.S.. That's where we feel confident. We, we want to get more quarters under our belt until we give guidance on the revenue for PKD. Of course, the bigger picture for us anyway, is that we're approaching the readout of the thalassemia data. That's a meaningfully larger launch that has potential in 2025. We may be in a scenario where we start to look at the collective guidance of multiple launches. Great. Thanks so much for taking our question. Sure. Thanks, Tess. One moment for our next question. Our next question comes from Danielle Brill of Raymond James. Your line is open. Hi, good morning, guys. Thank you so much for the question. I, I also have a question on the in licensed asset. I know there are also antibodies targeting TMPRSS6 in development. I was wondering if you could elaborate on why you think siRNA may be a superior modality in this indication. Is it just a more convenient dosing regimen, or do you think there might be an efficacy advantage as well? Thank you. Well, thanks a lot, Danielle, for the question. We think there are, as I noted earlier, potentially multiple opportunities for differentiation. TMPRSS6, we feel is now a well-established pathway. I mean, very simply, the 90% knockdown of TMPRSS6 has an uplift effect on hepcidin, which decreases iron, which ultimately lowers the red blood cell production. That, that thread through that mechanism, we feel through all of our diligence, very confident in. As I said, I think there will be opportunities for efficacy. Safety, of course, will be... You know, that's one when you look at some of the current opportunities therapeutically for patients, there's plenty of room for improvement. Then it could wind up also being a meaningful convenience opportunity because siRNA, classically, and particularly from the Alnylam platform, has proven that that is a mechanism that has delivered benefit to patients with lower interval of treatment. We're gonna look at all of that. It's very early, and we will start our IND-enabling studies this year, and then we'll report out our progress accordingly. Thanks so much. Sure. Thank you. Thank you. We're showing no additional questions, so we'll turn the call back to Brian Goff for a final comment. All right. Well, thank you all very much for participating in today's call and, of course, for your continued interest in Agios. As you heard this morning, we are really energized by the tremendous progress we continue to make across our portfolio. We are confident in our potential to deliver significant long-term value for both patients and shareholders. Thank you very much again, and we look forward to speaking with you soon. This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.