Q1 2024 Agios Pharmaceuticals Inc Earnings Call

Okay.

Operator: Good morning and welcome to AGIOS's first quarter 2024 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 today's conference is being recorded at AGIOS's request. I would now like to turn the call over to Chris Taylor, Vice President of Investor Relations and Corporate Communications for AGIOS. Please begin.

Good morning, and welcome to <unk> first quarter 'twenty 'twenty four conference call. At this time all participants are in a listen only mode there'll be a question and answer session. Please be advised that today's conference is being recorded and all Geos request I would now like to turn the call over to Chris.

Chris: Taylor, Vice President Investor Relations and corporate communications for <unk>.

Chris Taylor: Please begin.

Chris Taylor: Thank you, operator. Good morning, everyone, and welcome to Agios' conference call and webcast to discuss first quarter 2024 financial results and recent business highlights. You can access slides for today's call by going to the investor section of our website, agios.com. On today's call, I'm joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Gheuens, Chief Medical Officer, and Head of R&D. Tsveta Milanova, our Chief Commercial Officer, and Cecilia Jones, our Chief Financial Officer.

Chris Taylor: Yeah.

Chris Taylor: Thank you operator, good morning, everyone and welcome to <unk> Conference call and webcast to discuss first quarter 2024 financial results and recent business highlights you can access slides for today's call by going to the investors section of our website <unk> Dot com.

Taylor: On today's call I'm joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Hughes, Chief Medical Officer, and head of R&D.

Taylor: I don't know, Nova our Chief commercial Officer, and Cecilia Jones, Chief Financial Officer.

Chris Taylor: 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. However, actual results and events 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. And with that, I'll turn the call over to Brian. Good morning, everyone.

Taylor: 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 results.

Taylor: And events 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.

Taylor: With that I'll turn the call over to Brian.

Brian M. Goff: Good morning, everyone, and thank you for joining us. Our mission at Agios is to develop and deliver transformative medicines that improve and extend the lives of patients living with rare diseases, and we are off to a fast start in 2024.

Brian M. Goff: Good morning, everyone and thank you for joining us our mission at <unk> is to develop and deliver transformative medicines that elevate and extend the lives of patients living with rare diseases.

Brian M. Goff: We are off to a fast start in 2024.

Brian M. Goff: Our foundation today leverages Medipivet's novel mechanism of action, which focuses on overall red blood cell health and has been a key driver for our recent clinical results. On January 3rd, we reported positive data from the Phase III ENERGIZE study of our lead PK activator, Minipivet, marketed as Pyrokine, in patients with non-transfusion-dependent thalassemia. This study met both the primary endpoint of hemoglobin response rate, as well as both key secondary endpoints associated with change from baseline in facet fatigue score and average hemoglobin concentration, and we look forward to presenting these data at an upcoming medical meeting.

Brian M. Goff: Our foundation today Leverages mitigate that's novel mechanism of action, which focuses on overall red blood cell health and has been a key driver for our recent clinical results.

Brian M. Goff: On January 3rd we reported positive data from the phase III energized study of our lead PK activator mid tier that marketed as <unk> in patients with non transfusion dependent thalassemia.

Brian M. Goff: This study met both the primary endpoint of hemoglobin response rate as well as both key secondary endpoints associated with change from baseline in fact that fatigue score and average hemoglobin concentration and we look forward to presenting these data at an upcoming medical meeting.

Brian M. Goff: As a reminder, non-transfusion-dependent thalassemia accounts for approximately two-thirds of thalassemia in the US and has no FDA-approved treatment option. However, despite not requiring regular transfusions, it is increasingly understood that these patients experience a significant impact on their quality of life, a wide range of serious morbidity, and an elevated risk of premature death due to chronic hemolysis and ineffective erythrop Based on these data, our team is actively preparing for a potential launch in thalassemia in the U.S., complementing the ENERGIZE study in non-transfusion-dependent thalassemia. We continue to advance the Phase III Energized T Study of Midopibed in transfusion-dependent thalassemia.

Brian M. Goff: As a reminder, non transfusion dependent palace EMEA accounts for approximately two thirds of balancing here in the U S and has no FDA approved treatment options.

Brian M. Goff: Despite not requiring regular transfusions. It is increasingly understood that these patients experienced a significant impact on their quality of life a wide range of serious morbidities and an elevated risk of premature death due to chronic hemolysis.

Brian M. Goff: Effective erythropoiesis base.

Brian M. Goff: Based on these data our team is actively preparing for a potential launch in thalassemia in the U S.

Brian M. Goff: Complementing the energized study in non transfusion dependent thalassemia, we continue to advance the phase III energized T study admitted to hit that in transfusion dependent thalassemia. We expect to report data from this study in the second quarter, a slightly more refined timeframe than previously.

Brian M. Goff: We expect to report data from this study in the second quarter, a slightly more refined timeframe than previously communicated, and we plan to submit a single regulatory filing encompassing data from both ENERGIZE and ENERGIZE-T to the FDA by the end of the year. In parallel, we look forward to near-term milestones across several additional clinical programs in our pipeline, including completing enrollment in the Phase 3 portion of the Rise Up Study of Minipivet in Sickle Cell Disease by the end of this year and reporting data from four additional phase 3 studies by the end of 2025.

Brian M. Goff: <unk> and we plan to submit a single regulatory filing encompassing data from both energized and energized to the FDA by the end of the year.

Brian M. Goff: In parallel we look forward to near term milestones across several additional clinical programs in our pipeline.

Brian M. Goff: Including completing enrollment in the phase III portion of the rise up study admitted to that in sickle cell disease by the end of this year.

And reporting data from additional phase III studies by the end of 2025.

Brian M. Goff: Sarah will provide a detailed update on our progress and upcoming milestones across R&D in just a few minutes. Given the consistent positive data we've generated across the Mitopivet development program and the high unmet need in our target disease areas, we believe Mitopivet has the potential to transform the course of multiple hemolytic anemias by improving red blood cell health and to become a multi-billion dollar franchise. To help realize the full commercial potential of midipivet, and based on the strength of the energized data, our commercial organization is laser focused on building upon the infrastructure established through our current launch in pyruvate kinase deficiency, or PKD, to prepare for potential U.S. launches of midipivet in thalassemia in 2025 and in sickle cell disease in 2026.

Brian M. Goff: Sara will provide a detailed update on our progress and upcoming milestones across R&D and just a few minutes.

Brian M. Goff: Given the consistent positive data we've generated across the mid tier that.

Brian M. Goff: Development program.

Brian M. Goff: And the high unmet need in our targeted disease areas. We believe mid tier that has the potential to transform the course of multiple hemolytic anemias by improving red blood cell health and to become a multibillion dollar franchise.

Brian M. Goff: To help realize the full commercial potential admitted to that and based on the strength of the energized data. Our commercial organization is laser focused on building upon the infrastructure established through our current launch in pyruvate kinase deficiency or PK D to prepare for potential U.

Brian M. Goff: <unk> launches of mid Tibet in Dallas, EMEA in 2025 and in sickle cell disease in 2026.

Brian M. Goff: Tsveta will provide greater detail on the market opportunity in thalassemia and the team's robust preparation for launch, as well as an update on our current launch in PKD in just a bit. Finally, as you'll hear from Cecilia, we ended the first quarter with a strong cash position, with approximately $714 million in cash and investments on the balance sheet. Importantly, we have the potential to further bolster our cash position in the near term as Cervier announced FDA filing acceptance and priority review for a new drug application for voracidinib for the treatment of certain IDH mutant diffuse gliomas.

Brian M. Goff: <unk> will provide greater detail on the market opportunity in thalassemia and the team's robust preparation for launch as well as an update on our current launch a TKD in just a bit.

Brian M. Goff: Finally, as you'll hear from Cecilia we ended the first quarter with a strong cash position with approximately $714 million in cash and investments on the balance sheet.

Brian M. Goff: Importantly, we have the potential to further bolster our cash position in the near term as survey announced FDA filing acceptance and priority review for a new drug application for more aside nib for the treatment of certain <unk> mutant diffusely Omar.

Brian M. Goff: You'll recall that as part of the divestiture of Agios' oncology business to Servier, Agios retains rights to a potential $200 million milestone upon FDA approval of Voracidinib and 15% royalties on potential U.S. net sales. If approved, Vortisidinib would become a first-in-class targeted therapy for patients with IDH mutant glioma. And we look forward to the PDUFA action date of August 20th, 2024. With that, I'll turn the call over to Sarah.

Brian M. Goff: Youll recall that as part of the divestiture of <unk> oncology business the survey.

Brian M. Goff: <unk> retains rights to a potential $200 million milestone upon FDA approval of where aside nib and 15% royalties on potential U S net sales.

Brian M. Goff: If approved <unk> would become a first in class targeted therapy for patients with <unk> mutant Gliomas and we look forward to the <unk> action date of August 22024, with that I'll turn the call over to Sarah.

Sarah Gheuens: As we approach the top-line data readout for the Phase 3 ENERGIZE-T study of metapivab in transfusion-dependent thalassemia, I would like to highlight a few key elements of the metapivab development program in thalassemia. As a reminder, the Phase III program of MSF and thalassemia, namely ENERGIZE and ENERGIZE-T, was designed to deliver data As Brian mentioned, only patients with transfusion-dependent beta thalassemia, which represents one-third of U.S. patients, have an SVA-approved treatment option.

Sarah Hughes: Thanks, Brian.

Sarah Hughes: As we approach the topline data readout for the phase III energy T study of Mr. FIFA in transfusion dependent thalassemia I would like to highlight a few key elements of the new talked about development program in Dallas CEO.

Sarah Hughes: As a reminder, the phase III program with Mcafee founder solid senior, namely energized and energize fee was designed to deliver data across all sub populations of thalassemia.

Sarah Hughes: I'll start and Beth policy and populations with different transfusion needs.

Sarah Hughes: As Brian mentioned only patients with transfusion dependent beta thalassemia, which represents one third of U S patients have an SBA approved treatment option.

Sarah Gheuens: The other two-thirds of patients in the U.S., including all patients with alpha thalassemia and those patients with beta thalassemia who are non-transfusion-dependent, have no approved, It is a common misperception that nontransfusion-dependent, or NTD, thalassemia patients are less sick, when the reality is that these patients suffer from a poor quality of life and a high rate of serious morbidities, including thrombosis and premature death. This population, which represents approximately two-thirds of total Palestinian patients in the U.S., has a high unmet need for any, This unmet need was strongly reinforced through our Phase III energized study by the speed of enrollment, the total number of patients enrolled, and the high completion and rollover rates we observed. We were very pleased to announce positive results from this study in January and are eagerly awaiting the opportunity to present more complete results at an upcoming medical meeting.

Sarah Hughes: Two thirds of patients in the U S, including outpatients with Alpha thalassemia and those patients with beta thalassemia, who are non transfusion dependent have no approved treatments.

Sarah Hughes: It is a common misperception that non transfusion dependent or NTT thalassemia patients are sick.

Sarah Hughes: When the reality is that these patients suffer from a poor quality of life and a high rate of serious morbidities, including from both LP maturing debt.

Sarah Hughes: This operation, which represents approximately two thirds of the total calcium that patients in the U S is a high unmet need for any treatment.

Sarah Hughes: The unmet need with strongly reinforced through our phase III energize study by the speed of enrollment the total number of patients enrolled in a high completion and rollover rates to be up there.

Sarah Hughes: We were very pleased to announce positive results from this study in January and are eagerly awaiting the opportunity to present more complete results at an upcoming medical meeting.

Sarah Gheuens: Turning to those results, our goal was to build upon our phase 2 findings with a more rigorous way to measure a hemoglobin response in the phase 3 energized trial, which we defined as an increase of equal or more than 1 gram per deciliter in average hemoglobin concentrations from week 12 through week 24, compared to baseline, but in a much larger trial. We were excited to be able to announce success in this trial, as treatments with 100 milligrams metapifaz-BID demonstrated a highly statistically significant result on the primary endpoint of hemoglobin response rate, with 42.3% of patients in the treatment arm achieving a hemoglobin response versus 1.6% of patients in the placebo arm.

Sarah Hughes: Turning to those results our goal is to build upon our phase two findings with a more rigorous way to measure hemoglobin response in the phase III <unk> trial, which we defined in the primary endpoint is an increase of equal or more than one gram per deciliter in average hemoglobin concentrations from week 12 through week 24.

Sarah Hughes: Paired with baseline, but has a much larger trial.

Sarah Hughes: We were excited to be able to announce success in this trial as treatments with 100 milligrams, we talk about VIP demonstrated a highly statistically significant result on the primary endpoint of hemoglobin response rate with 42, 3% of patients in the treatment arm, achieving a hemoglobin response versus one 6% of patients in the placebo.

Sarah Gheuens: In addition, treatment with Mitopifaz also resulted in statistically significant improvements in both key secondary endpoints, including a change from baseline in average FAFSA fatigue score, an important patient-reported measure of how patients feel. In line with its novel mechanism of action that improves overall red blood cell health, metapepat is the first molecule that has shown in a randomized controlled trial that it does not only improve hemoglobin but actually makes In addition, across the primary and secondary endpoints, all pre-specified subgroup analyses favored mitopibab compared to placebo, suggesting that no single subgroup was responsible for driving the results, which supports our aim to file for a broad label covering all thalassemia subtypes.

Sarah Hughes: Arm.

Sarah Hughes: In addition treatment with me talk about also resulted in statistically significant improvements in both key secondary endpoints, including a change from baseline in average.

Sarah Hughes: Score and important patient report this measure of how patients feel.

Sarah Hughes: In line with its novel mechanism of action that improves overall red blood cell health myths up about is the first molecule that has shown in a randomized controlled trial that it does not only improve hemoglobin that actually makes people without senior field less fatigue.

Sarah Hughes: In addition across the primary and secondary endpoints, all prespecified subgroup analyses favorite restarted up compared to placebo, suggesting that no single subgroup was responsible for driving the result, which supports our aim to solve for a broad label covering all thalassemia subtypes.

Sarah Gheuens: Let me highlight three key reasons why we are excited about the upcoming readout in Transfusion Dependent Policy. First, it is important to recall that regardless of a patient's transfusion needs, thalassemia is a hemolytic anemia. By upregulating PK activity and improving overall red blood cell health, MSF's novel mechanism of action directly addresses the underlying pathophysiology of hemolysis in all thalassemia subjects.

Sarah Hughes: Turning to interject fee, let me highlight three key reasons why we are excited about the upcoming readout in transfusion dependent thalassemia.

Sarah Hughes: First it is important to recall that regardless of the patient's transfusion need dulcea isn't hemolytic anemia by escalating PK activity and improving overall red blood cells help me talk about the novel mechanism of action directly addresses the underlying pathophysiology of hemolysis and outbound senior subtypes.

Sarah Gheuens: Second, this is a similar approach to the one we took for our PK deficiency program. In that case, in a Phase III Activate-Seq study of metaphebots in regularly transfused adults with pyruvate kinase deficiency, metaphebots demonstrated a statistically significant and clinically meaningful reduction in transfusion burden. These data, together with positive data from the Phase 3 ACTIVATE study in patients with PK deficiency who are not regularly transfused, led to FDA approval of Mitapiva for adults with PK deficiency regardless of transfusion status. And we look forward to the potential to achieve the same in South Africa.

Sarah Hughes: Second this is a similar approach to the one we took for our PK deficiency program.

Sarah Hughes: In that case and the phase III activate these steady Amit that we got in regularly transfused adults with pyruvate kinase deficiency, Mitch talked about demonstrated a statistically significant and clinically meaningful reduction in transfusion burden.

Sarah Hughes: These data together with positive data from the phase III <unk> study in patients with PK deficiency, who are not regularly transfused led to FDA approval of Mcduffie bus for adults with PK deficiency, regardless of transfusion status and we look forward to the potential to achieve the same imbalance senior.

Sarah Gheuens: And third, in line with Mitopitot's mechanism of action, we have seen consistency in the data with improvements in hemolysis and ineffective erythropoiesis in clinical studies across three hemolytic anemias, namely TK deficiency, sickle cell disease, and nontransfusion-dependent thalassemia. As a reminder, the primary endpoint of ENERGY-C is a transfusion reduction response defined as a 50% or greater reduction in transfused red blood cell units with a reduction of equal or more than two units of transfused red blood cells in any consecutive 12-week period through week 48 compared with baseline.

Sarah Hughes: And third in line with Mr. Africa mechanism of action, we have seen consistency in the data with improvements intermodal assist and ineffective erythropoiesis and clinical studies across three hemolytic anemia, namely PK deficiency sickle cell disease, and non transfusion dependent thalassemia.

Sarah Hughes: As a reminder, the primary endpoint of Energizer.

Sarah Hughes: Transfusion reduction response.

Sarah Hughes: And at a 60% or greater reduction in transfused red blood cell units with a reduction of equal or more than two units of transfused red blood cells in any consecutive 12 week period through week 48, compared with baseline.

Sarah Gheuens: This definition allows two ways for patients to achieve a reduction in transfusion burden. First, via an increased time interval between transfusions, or second, through the use of fewer units or both. In order to standardize as much as possible the standards of care in this large global trial, each patient had a specific hemoglobin threshold value that was calculated based on their individual transfusion history prior to enrolling in the trial. The hemoglobin threshold value determines the level at which they will receive a transfusion in the trial. As the mechanism of action of Mitapevac focuses on increasing red blood cell health and decreasing hemolysis, we are hoping to maintain hemoglobin levels above this threshold and reduce the need for transfusions.

Sarah Hughes: This definition allow us two ways for patients to achieve a reduction in transfusion burden.

Sarah Hughes: Yes, an increase time interval between transfusions or second so the use of fewer units or both.

Sarah Hughes: In order to standardize as much as possible the standard of care in this large global trial each patients had a specific hemoglobin threshold value that was calculated based on their individual transfusion history prior to enrolling in the trial.

Sarah Hughes: Each patient's individual hemoglobin threshold value determines the hemoglobin value by which they will receive a transfusion in the trial as.

Sarah Hughes: As the mechanism of action of mix up as our focus is on increasing red blood cell health and decreasing hemolysis, we are hoping to maintain hemoglobin levels above this threshold and reduce the need for transfusions.

Sarah Gheuens: We designed this study by incorporating learnings from prior studies as well as agency feedback and believe the primary endpoint, the dynamic assessment period, reflects what matters to patients and physicians as well as regulators. We now look forward to the readout of this study in the second quarter and are planning to submit a single regulatory filing to the FDA and compacting data from both ENERGIZE and ENERGIZE-T by the end of this year, seeking a label that covers people living with all subtypes of talismans.

Sarah Hughes: We designed this study by incorporating learnings from prior studies as well as agency feedback and believe the primary endpoints dynamic assessment periods reflect what matters to patients and physicians as well as regulators.

Sarah Hughes: We now look forward to the readout of this study in the second quarter and are planning to submit a single regulatory filing to the FDA and compacting data from both energized and energized by the end of this year seeking a label that covers people listen with all subtypes of thalassemia.

Sarah Gheuens: Turning to sickle cell disease, enrollment in the Phase III portion of the MIT SAPIBA study continues to progress, and we are on track to complete enrollment by the end of the year. We have increasing conviction about the role of metabolism in sickle cell disease, where we believe we have the potential to be both best in class and first in class. We look forward to reporting top-line data from this 52-week study next year and believe firmly in Metapifa's potential to address the high unmet need in this disease by improving anemia, making patients feel better, and reducing the sickle cell pain crisis. We also remain on track to deliver on all milestones across the rest of our advancing pipeline.

Sarah Hughes: Turning to sickle cell disease and.

Sarah Hughes: Enrolment in the phase III portion of the study of Mr. <unk> as that continues to progress and we are on track to complete enrollment by the end of the year, we have increasing conviction about the golar <unk> talked about the sickle cell disease, where we believe we have the potential to people best in class and first in class.

Sarah Hughes: We look forward to reporting topline data from this 52 week study next year and believe firmly in the top about the potential to address the high unmet need in this disease by improving anemia patients feel better and reducing sickle cell pain crisis.

Sarah Hughes: We also remain on track to deliver on all milestones across the rest of our advancing pipeline.

Sarah Gheuens: This quarter, we commence dosing in the Phase 1 study of AG181, an oral phenylalanine hydroxylase, or PAH, stabilizer for phenylketonuria, abbreviated as PKU, a patient population with limited treatment options. We are excited about the potential to introduce a novel mechanism of action for PKU treatment and look forward to providing an update on next steps as enrollment progresses. Based on the data generated in the Phase 2A study of our novel PK activator, AG946, in lower-risk MDS, we plan to increase the doses evaluated in the upcoming Phase 2B study, which we expect to initiate in mid-2024.

Sarah Hughes: This quarter, we commenced dosing in the phase one study of AG 181, and oral Pheno alanine hydroxylase or.

Sarah Hughes: H stabilizer for fan Youll get an abbreviated as PKU patient population with limited treatment options.

Sarah Hughes: We are excited about the potential to introduce a novel mechanism of action for PKU treatment and look forward to providing an update on next steps as enrollment progresses.

Based on the data generated in the Phase Iia study of our novel <unk> Activator AG 946 in lower risk Mds, we plan to increase the doses evaluated in the upcoming phase II B study, which we expect to initiate in mid 2024.

Sarah Gheuens: And in Pediatric PTA Deficiency, we expect to complete enrollment in the Phase 3 Activate Kids Study in the middle of this year, and we also now expect to report top-line data from the Phase 3 Activate Kids T Study in mid-2024, sooner than our original projection for the year. This is a very exciting time at Agios, and we look forward to providing additional readouts and progress as we proceed through the year. In particular, we're looking forward to sharing with you the status of submissions for EHA when they are made public in a couple of weeks. With that, I will now turn the call over to Tsveta.

Sarah Hughes: And in pediatric PK deficiency, we expect to complete enrollment of the phase III <unk> study in the middle of this year and we also now expect to report topline data from the phase III activate T study in mid 2024 sooner than our original projection of year end.

Sarah Hughes: This is a very exciting time at <unk> and we look forward to providing additional readouts in progress as we proceed through the year in particular, we're looking forward to sharing with you the status of submissions for Ehealth. When they are made public in a couple of weeks with that I will now turn the call over to setup.

Tsveta Milanova: Sarah, today a diagnosis of thalassemia can be daunting for patients and their families. Regardless of the disease subtype, treatment options are limited, and the burden of the disease as well as the associated cost of care is significant. All forms of thalassemia, including non-transfusion-dependent thalassemia, bring higher rates of serious morbidities, reduced quality of life, and a heightened risk of premature death. There are approximately 6,000 diagnosed adults living with leukemia in the U.S.

Setup: Thanks Sarah.

A diagnosis of the lithium yet can be daunting for patients and their families.

Setup: Regardless of the disease subtype treatment options are limited and the burden of disease as well as the associated cost of care is significant.

Speaker Change: All forms of Dulles, EMEA, including non transfusion dependent at Telus EMEA.

Speaker Change: Bring higher rates of serious morbidities reduced quality of life and a heightened risk of premature death.

Speaker Change: There are approximately 6000 diagnosed about leaving with the leukemia in the U S.

Tsveta Milanova: Approximately 4,000 of whom are non-transfusion dependent and have no available treatment options today. As Sarah mentioned, this patient population was studied in our ENERGYX clinical trial, which demonstrated the benefits of Mikativa in non-transfusion-dependent thalassemia patients. The remaining 2,000 are transfusion-dependent and have no oral treatment options.

Speaker Change: Approximately 4000 of whom are non transfusion dependent and have no available treatment options today.

Speaker Change: As Sarah mentioned this patient population was static in our <unk> clinical trial, which demonstrated the benefits of <unk> in non transfusion dependent thalassemia patients.

Speaker Change: The remaining 2000 are transfusion dependent and have no oral treatment option.

Tsveta Milanova: We are eagerly awaiting the data from our ENERGY-C study in the second quarter, which is focused on these transfusion-dependent patients. Our goal with Mitativa is to transform the treatment of thalassemia by becoming the first therapy approved for all subtypes of thalassemia, galvanized by the positive data from the ENERGYiST study and the potential for positive data from other ENERGYiST teams. Our commercial organization is actively preparing to address this high unmet need with a potential launch in thalassemia next year in the U.S. As we have highlighted, the Palestinian market in the U.S. has more favorable commercial dynamics than decay deficiency.

Speaker Change: We are eagerly awaiting the data from our <unk> study in the second quarter.

Speaker Change: Which is focused on this transfusion dependent patients.

Speaker Change: Our goal with meet the fever is to transform the treatment of <unk> EMEA by becoming the first therapy approved for all subtypes of the disease.

Speaker Change: Galvanized by the positive data from <unk> study and the potential for positive data from energized team.

Speaker Change: Our commercial organization is actively preparing to address this high unmet need with a potential launch into leukemia next year in the U S.

As we have highlighted that the lithium market in the U S has more favorable commercial dynamics that became efficiency.

Tsveta Milanova: In addition to the data we are generating through the MITAPIVA Clinical Development Program, we believe there are three key factors that have the potential to support adoption of MITAPIVA in thalassemia in the U.S. First, driven by the availability of newborn screening and well-established ICD-10 codes, the diagnosis rate for thalassemia is high, with many patients diagnosed before adulthood. Second, both patients and providers are concentrated in a limited number of centers, with approximately 50% of all diagnosed patients treated at fewer than 150 affiliated practices, providing a clear focus for our initial launch.

Speaker Change: In addition to the data we are generating through <unk> clinical development program. We believe there are three key factors that have the potential to support adoption of makeup be about Intel anemia in the U S.

Tsveta Milanova: And third, our clinical trial sites in the U.S. are in some of the main centers of excellence, so many treating physicians will have first-hand experience with Mitopilab. Given this data and META-PIVA's target product profile, we believe we are well positioned to provide a potential foundational treatment option for patients with thalassemia, regardless of subtype. Our team is focused on four areas of the Latina US launch preparation.

Speaker Change: Alright, great.

Speaker Change: Driven by the availability of newborn screening and well established ICD. Thanks Paul.

Speaker Change: I'll just go right into leukemia is high with many patients diagnosed before others could.

Speaker Change: Thanks, Bob.

Speaker Change: Both patients and providers are concentrated in a limited number of centers with approximately 50% of all diagnosed patients treated at fewer than a funded and 50 of deviated practices.

Speaker Change: Providing a clear focus for our initial launch.

Speaker Change: And third our clinical trial sites in the U S or in some of the main centers of excellence. So many treating physicians will have firsthand experience with me that vivat.

Speaker Change: Given these data and meet the target product profile. We believe we are well positioned to provide a potential foundational treatment options for patients with pellets EMEA regardless of subtype.

Our team is focused on four areas of <unk> U S launch preparation.

Tsveta Milanova: First, we continue to advance extensive market research and claim data analysis to further refine our market insights and our HCP targets. Second, we are rolling out a disease education campaign in the coming weeks designed for both patients and clinicians, highlighting the long-term complications and burden of disease across all thalassemia subtypes, particularly non-transfusion dependent patients who suffer from the misconception that they are at less risk. We are executing a disciplined expansion of our commercial and medical teams to right-size the organization for a successful launch in this larger, but still rare, market.

Speaker Change: Chris we can.

Speaker Change: Continued to advance extensive market research and claims data analysis to further refine our market insights and our ACP targeting.

Speaker Change: Second we are rolling out a disease education campaign in the coming weeks designs for both patients and clinicians.

Speaker Change: Highlighting the long term complications and burden of disease across all Philips EMEA subtypes.

Speaker Change: Thank you Ali non transfusion dependent patients who suffer from the misconception that they are at less risk.

Speaker Change: Alright, we have.

Speaker Change: Using a disciplined expansion of our commercial and medical teams to right size. The organization for a successful launch in this larger but still rare market and.

Tsveta Milanova: [inaudible] Our market access team is already engaging with payers on disease state education. I'm proud that our team has obtained broad market access for pyrokines in PK deficiency, and we look forward to the same strong outcome in thalassemia. In addition to the U.S., we aim to maximize the potential of markets outside the U.S. through coordinated regulatory filings, which we intend to pursue with one or more

Speaker Change: And fourth.

Speaker Change: Our market access team is already engaging with fans on disease State education.

Speaker Change: Proud that our team has obtained broad market access for our final guidance in PK deficiency, and we look forward to the same strong outcome in the leukemia.

Speaker Change: In addition to the U S. We aim to maximize the potential of markets outside the U S.

Speaker Change: The latest regulatory filings, which we intend to partner with one or more partners.

Speaker Change: These markets include the Gulf region, which is home to approximately 70000 thalassemia patients and some of the leading treatment centers in our clinical trials.

Cecilia Jones: This market includes the Gulf region, which is home to approximately 70,000 thalassemia patients and some of the leading treatment centers in our clinical trials. Let me now provide an update on the current launch of pyrukine in PK deficient patients. In the first quarter of 2024, we generated $8.2 million in net pyrokine revenue compared to $7.1 million in the fourth quarter of 2023. In the U.S., a total of 188 patients have completed a prescription enrollment form, including 10 in the first quarter of 2024, a 6% increase versus the prior quarter.

Let me now provide an update on the current launch of <unk> in PK deficiency.

Speaker Change: In the first quarter, our blended plan before we generated $8 2 million in net <unk> revenue compared to seven.

Speaker Change: $1 million in the fourth quarter of 2023.

Speaker Change: In the U S. A total of 188 patients have completed a prescription enrollment form including 10 in the first quarter of blend to 24, 6% increase versus the prior quarter.

Cecilia Jones: This has translated into net 120 patients on therapy, a 10% increase versus the prior quarter. Patients on therapy continue to stem from a growing and diverse prescriber base of 162 physicians and represent a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population in the U.S. We continue to be encouraged by the persistency of patients on treatment and remain focused on efficiently identifying providers likely to treat patients with PK deficiencies.

Speaker Change: This has translated into net of 120 patients on therapy as bandwidth and increase versus the prior quarter.

Speaker Change: Patients on therapy continues to grow.

Speaker Change: Boeing and the prescriber base of 162 physician and represent a broad demographic and disease manifestation range that is consistent with the adult PK deficiency population in the U S.

Speaker Change: We continue to be encouraged by the parties plus CF patients on treatment and remain focused on efficiently identifying providers likely to treat patients with begin efficiency.

Cecilia Jones: We believe the capabilities we continue to strengthen through the current launch, including efficient targeting analytics, patient and HCP awareness and education, and patient access, will provide a firm foundation to maximize potential future U.S. launches of metabiotes in thalassemia in 2025 and in sickle cell disease in 2026. Above all, Agios is once again incredibly proud to be pioneering a potential new therapy for these two underserved patient populations. With that, I will turn the call over to Cecilia.

Speaker Change: We believe the capabilities, we continue to strengthen towards the current launch, including additional targeting analytics patients and ACP awareness and education and patient access we will provide a firm foundation to maximize potential future U S launch of <unk>.

Speaker Change: <unk> in 2025 and in sickle cell disease in 2026.

Speaker Change: Above all.

Speaker Change: <unk> is a once again incredibly proud to be pioneering a potential new therapy for this underserved patient population with that I will turn the call over to Cecilia. Thanks.

Cecilia Jones: Thanks, Tsveta. Our first quarter 2024 financial results can be found in the press release we issued this morning, and more detail will be included in our 10th Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. First quarter 2024 net pyrotherm revenue was $8.2 million, an increase of $2.6 million compared to the first quarter of 2023. Consistent with other rare disease launches, growth to net has been and is expected to be in the 10 to 20 percent range on an annual basis.

Thanks for that.

Cecilia Jones: First quarter 2024 financial results can be found in the press release, we issued this morning and more detail will be included in our 10-Q, which will be filed later today.

Cecilia Jones: Cost of sales for the quarter was $0.6 million. R&D expenses were $68.6 million for the first quarter, an increase of $1.3 million compared to the first quarter of 2023. This increase was primarily driven by an increase in process development expenses offset by a decrease in workforce-related expenditures. SG&A expenses were $31 million for the first quarter, an increase of $2.6 million compared to the prior year quarter.

Cecilia Jones: Let me now take a moment to provide some context and highlight a few key points.

Cecilia Jones: First quarter 2024, net <unk> revenue was $8 2 million, an increase of $2 $6 million compared to the first quarter of 2023.

Cecilia Jones: Consistent with other rare disease granted gross to net has been and is expected to be in the 10% to 20% range on an annual basis.

Cost of sales for the quarter was zero point $6 million.

Cecilia Jones: R&D expenses were $68 $6 million for the first quarter, an increase of $1 $3 million compared to the first quarter of 2023. This.

Cecilia Jones: This increase was primarily driven by an increase in process development expenses offset by a decrease in workforce related expenditures.

G&A expenses were $31 million for the first quarter, an increase of $2 $6 million compared to the prior year quarter.

Cecilia Jones: This was primarily driven by an increase in commercial-related activities as we prepare for the potential approval of pyrokine intellectual property. As a reminder, as part of the divestiture of our oncology business to Serbia, we retain rights to a potential $200 million milestone upon FDA approval of oral siren and 15% royalties on potential U.S. net sales. We ended the quarter with cash, cash equivalents, and marketable securities of approximately $714.3 million. We expect that this balance, together with anticipated product revenue, interest income, and the potential for a silo-net milestone, will enable the company to fund its operating expenditures and capital expenditures through several value-creating milestones and at least into 2026.

Cecilia Jones: This was primarily driven by an increase in commercial related activities as we prepare for the potential approval of Viracon incentives seen yet.

Cecilia Jones: As a reminder, as part of the divestiture of a quality business to Serbia, we retain rights to a potential 200 million dollar milestone upon FDA approval of Lora side of nib, and 15% royalties on potential U S net sales.

Cecilia Jones: We ended the quarter with cash cash equivalents in marketable securities of approximately $714 $3 million. We expect that this balance together with anticipated product revenue interest income and the potential for upside in that milestone will enable the company to fund our operating expenditures and capital.

Cecilia Jones: Expenditures through several value, creating milestones and at least into 2026.

Cecilia Jones: This guidance does not include cash inflows that could extend a runway beyond 2026, including potential royalties or royalty monetization from Boros Aydinib, commercializing MetaPayment outside of the U.S. through one or more partnerships, or other potential strategic business or financial agreements. We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined cash allocation approach, and we prepare to support potential future launches of As we move toward additional potential value-creating milestones in the near term, I am confident that our strong balance sheet will enable us to execute from a position of strength. I will now turn the call back over to Brian for his closing remarks. Thanks, Cecilia.

Cecilia Jones: This guidance does not include cash inflows that could extend that runway beyond 2026, including the potential royalties or royalty monetization from both outside the nib commercializing Mr favorite outside of the U S through one of our partnerships or other potential strategic business or financial agreement.

Cecilia Jones: We remain focused on creating shareholder value, including by proactively managing our cost base and deploying a disciplined capital allocation approach as we prepare to support potential future launches of Paragon.

Cecilia Jones: As we move toward additional potential value, creating milestones in the near term I am confident that our strong balance sheet will enable us to execute from a position of strength.

I will now turn the call back over to Brian for his closing remarks.

Brian M. Goff: Thanks Cecilia. Driven by a novel and differentiated mechanism of action that improves red blood cell health, and a clinical data package that includes positive data spanning three hemolytic anemias, we believe Mitopivet is poised to become a first-in-class and best-in-class treatment option for multiple indications, with potential to become a multi-billion dollar franchise. I'm very proud of our team for steadily delivering significant progress, and looking ahead, I'm truly excited about the catalyst-rich 24 months in front of us.

Brian M. Goff: Thanks, Cecilia driven by our novel and differentiated mechanism of action that improves red blood cell health and our clinical data package that includes positive data spanning three hemolytic anemias. We believe <unk> is poised to become a first in class and best in class treatment.

Brian M. Goff: <unk> for multiple indications and with potential to become a multibillion dollar franchise.

Brian M. Goff: Very proud of our team for steadily delivering significant progress in looking ahead.

Brian M. Goff: Truly excited about the catalyst rich 24 months in front of us.

Brian M. Goff: As we continue to take steps toward realizing our vision of becoming a leading rare disease company, 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 developing and delivering transformative medicines that elevate and extend the lives of patients living with rare diseases. And all of our partners, including the patients, physicians, caregivers, and participants in our clinical development program. With that, we'll now open the call for questions. Thank you.

Brian M. Goff: As we continue to take steps towards realizing our vision of becoming a leading rare disease company. 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 developing and delivering transformative medicines that elevate and extend the lives of patients living with rare diseases.

Brian M. Goff: And all of our partners, including the patients physicians caregivers and participants in our clinical development programs with that we'll now open the call for questions.

Speaker Change: Thank you.

Operator: To ask your question, you'll need to press star 1-1 on your telephone. To withdraw your question, please press star 1-1 again. We ask that you please limit your questions to one question and one follow-up. Please stand by while we compile the Q&A roster. One moment for our first question. And our first question will come from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Speaker Change: To ask a question you will need to press star one on your telephone to assure your question. Please press star one again.

Speaker Change: We ask that you. Please limit your questions to one question and one follow up.

Speaker Change: Please standby, while we compile the Q&A roster.

Speaker Change: One moment for your first question.

Speaker Change: And our first question will come from the line of Gregory Windsor with RBC capital markets. Your line is now open.

Gregory James Renza: Great. Thanks. Hey, good morning, Brian and team. Congratulations on the progress, and thanks for taking my questions. Sure. Thanks, Greg. Thank you. Brian, we certainly appreciate the more precision and timing for the ENERGIZE-T data. I'm just curious, just narrowing it at least from mid-year to second quarter, can you just comment a bit on sort of the relevance factors now, what needs to be done, and maybe some of the influences around just getting it to that narrower, earlier timeframe in the second quarter? And maybe related to that, just remind us just the mechanics of patients rolling over to the open label.

Gregory Allen Harrison: Great. Thanks, Hey, good morning, Brian and team congratulations on the progress and thanks for taking my questions sure. Thanks, Greg. Thank you Bryan we certainly appreciate the more precision the timing for the energized T data I'm just curious.

Gregory Allen Harrison: Narrowing it at least for a mid year or two.

Speaker Change: Second quarter can you just comment a bit on sort of the relevant factors now what needs to be done.

Speaker Change: And maybe some of the influences around just getting it to that narrow it earlier timeframe on the second quarter and maybe related to that just remind us just the mechanics on patients rolling over to the open label extension. Thanks, So much.

Brian M. Goff: Sure, thanks Greg. I'm going to let Sarah talk about the mechanics, but I will say that we are very much looking forward to the data. It's a very special time at Agios because everyone who's followed us, and I know, Greg, you certainly have been there, knows that we were delighted to have the ENERGIZE data back in January, and this study, ENERGIZE-T, is twice the length. ENERGIZE was a 24-week study. This is 48 weeks. And we know there's a lot of interest, and so we were delighted to give, as you said, a little more granularity on the timing, but Sarah, do you want to talk about some of the mechanics?

Speaker Change: Sure. Thanks, Greg I'm going to let Sarah to talk about the mechanics, but I will say that we are.

Sarah Gheuens: Sure, and so the granularity of the timing is driven by the patient. The last couple of patients in the study, their decisions to roll over into open-label extension or not, because as you know, if a patient had decided not to go into open-label, then they would need to taper down the drug and then have a safety follow-up visit, which could, which really drives a time frame that creates basically a seven-week difference between potential readouts.

Speaker Change: We're very much looking forward to the data.

Speaker Change: It's a very special time at our Geos, because everyone, who has followed us and I know Greg you certainly have been there knows that we were delighted to have the energized data back in January and.

Sarah Hughes: This study energize T is twice the lengths that was energized was the 24 week study. This is 48 weeks.

Sarah Hughes: And we know there's a lot of interest and so we were delighted to give as you said a little more granularity on the timing, but Sarah you want to talk about some of the mechanics sure until the granularity of the timing is driven by the patient. The last couple of patients in the study there are decisions to rollover into the open label extension or not because.

Sarah Hughes: As you know if a patient would have decided to not go into open label, then they would need to taper down the drug and then have a safety follow up visit which could which really drive the timeframe.

Sarah Hughes: That creates basically a seven week difference between potential.

Sarah Gheuens: Now we have much more precision around that type of information, and we can narrow our time frame. So that's why we've updated our guidance today. We're very excited about where we are right now, and the team is very focused on delivering the next steps for this.

Sarah Hughes: Potential readouts. So now we have much more precision around that type of information is so we can narrow our timeframe. So that's why we've updated our guidance to date, we're very excited about about where we are right now and the team is very focused on delivering the next the next steps for this specific trial.

Brian M. Goff: Yeah, so this was the exact same scenario that we faced last year when we read out the RiseUp Phase 2 data for sickle cell disease, and of course, the same for Energize in January. The big picture that I'll just end with here is that our intent, as we noted in our prepared comments, is to file both studies together to target a label that encompasses all thalassemia patients, all subtypes. And all that said, of course, we look forward to the data, but we're already in a significant position of strength given the Energize data and the fact that, as you heard from Tsveta, that addresses already two-thirds of the population in the U.S. with non-transfusion-dependent thalassemia.

Sarah Hughes: Yes. So this was the exact same scenario that we faced last year when we read out the rise of phase III data for sickle cell disease and of course, the same for energized in January.

Sarah Hughes: The big picture that I'll, just end with here is that.

Sarah Hughes: Our intent as we noted in our prepared comments is to file both studies together to target a label that encompasses all style of CVA patients all subtypes and.

Sarah Hughes: All that said of course, we look forward to the data, but we're already in a significant position of strength given the energized data and the fact that as you heard from Scott.

Sarah Hughes: That addresses already two thirds of the population of the U S with non transfusion dependent thalassemia.

Gregory James Renza: That's great, Brian. Thank you very much.

Sarah Hughes: That's great Brian. Thank you very much maybe just a follow up just broadly on the on the landscape certainly with PK activation competition.

Brian M. Goff: Maybe just a follow-up just broadly on the landscape, certainly with the D.K. Activation Competition. To have a pivot from NOVO, maybe having some timelines now established, what do you make of that? How do you think about the landscape longer term?

Speaker Change: What the Teva Pitman from from Novo, maybe having some some timelines now established what do you make of that how do you think about the landscape longer term you are certainly moving moving fast, but as you think about the jockeying between between the two.

Brian M. Goff: You're certainly moving fast with the jockeying between the two offices. Yeah, thanks for the question. I mean, certainly, we take a lot of pride in the fact that we're the worldwide leader in PK activation. And I think given some of the recent competitive updates that have been made public, specifically with the other PK activator, Etavo Pivet from Novo Nordisk, we took note of the most recent updated timelines. And that's why you heard in our prepared comment that we often say we feel very confident in our best-in-class positioning.

Brian M. Goff: Two offerings for patients ultimately thanks again, yes. Thanks for the question I mean, certainly we take a lot of pride in the fact that we are the worldwide leader in PK activation.

Teva Pitman: And I think given some of the recent competitive updates that have been made public specifically with the other PK activator Tahoe pivot from Novo Nordisk.

Brian M. Goff: We took note of the most recent updated timelines and.

Brian M. Goff: That's why you heard in our prepared comments.

Brian M. Goff: That we've often said we feel very confident in our best in class positioning we feel increasingly confident now across both thalassemia and certainly sickle cell disease with first in class potential and that all leads to.

Brian M. Goff: We feel increasingly confident now across both thalassemia and certainly sickle cell disease with first-in-class potential, and that all leads to this franchise having multi-billion dollar potential with midipivad. We're in a really significant position of strength.

Brian M. Goff: This franchise, having multibillion dollar potential with <unk>.

Brian M. Goff: A real significant position of strength.

Tsveta Milanova: Yeah, absolutely, and when we think commercially about thalassemia, we are definitely very much ahead. What we've heard from NOVA is that they'll be reading out data in 2026 for their Phase 2 study, and we don't know about their commitment to Phase 3.

Speaker Change: Yeah, absolutely and why do we think the <unk> for thalassemia, we're definitely very much ahead.

Speaker Change: Across mobile is that there'll be reading out data in <unk> 2000, and seek their phase II study.

Brian M. Goff: So for thalassemia, we're very excited to pioneer the way and have a treatment option for all thalassemia patients. In sickle cell disease, equally exciting on our part, we are progressing with the recruitment of our clinic, phase 3 clinical trial, and everything is going on plan. What we've heard with Etabo Pivot is that they are expecting sickle cell disease data in 2027, which will put them behind our anticipated launch in 2026, again giving us an opportunity to basically bring the first innovative product with the potential to hit on all the clinically meaningful and commercially meaningful endpoints of hemoglobin improvement, reductions in VOC, and improvement in quality of life, so we're excited to be moving forward. And this is where we're taking full advantage.

Speaker Change: And we don't know about their commitment to phase III adult portal Lithemia, we're very excited by the way I was having on pigment options for our core auto lithemia patients in sickle cell disease up equally.

Brian M. Goff: <unk> on our part we are progressing with the recruitment of our Atlantic Phase three clinical trial everything.

Brian M. Goff: When we acquired which I thought would be or is it they are expecting sickle cell disease data in 2027, which will be put them behind our anticipated launch in 2026.

Brian M. Goff: Given us an opportunity.

Brian M. Goff: Basically, bringing the first in all of these products with the potential to either all of the clinically meaningful and commercially meaningful influence of hemoglobin <unk> reductions and EOC in April may and quality of life sale. We're excited to be moving forward and this is where we're taking full advantage of spread his expertise deep expertise in rare disease.

Operator: And this is where we're taking full advantage of Tsveta's expertise, deep expertise in rare disease launches. This is, you know, this is what you live for, a chance to change the lives of patients, and thalassemia is certainly that scenario. And this launch has the potential to be next year, so it will come soon. Thank you.

Brian M. Goff: These launches.

Brian M. Goff: This is this is what you live for us a chance to change the lives of patients in thalassemia certainly that scenario in this launch has the potential to be next year, so coming soon.

Brian M. Goff: Okay.

Divya Rao: Our next question will come from the line of Divya Rao with TD Cowan. Your line is now open.

Speaker Change: Thank you.

Speaker Change: Our next question will come from the line of <unk> Rao with TD Cowen. Your line is now open.

Speaker Change: Good morning. This is Debbie on for Mark Thanks for your question.

Debbie: One of them.

Debbie: South EMEA, the transfusion dependent thalassemia trial coming up can you walk us through the powering assumptions for the primary endpoint and then I have a follow up.

Divya Rao: Sure, thanks Divya. Sorry, you want to take that? Yes, so we haven't spoken in detail about the powering assumption underlying the number, but we

Speaker Change: Sure. Thanks, Steve, Yes, or you want to take that.

Sarah Gheuens: Yes, so we haven't spoken in detail about the powering assumption underlying the number, but we, of course, have leveraged all the information available to make sure that we have very good statistical justification for this trial and feel confident in the primary endpoint and the sample size that we have selected. The primary endpoint by itself, as you know, is a 50% reduction in any 12-week rolling period, which we believe can provide a very meaningful assessment of a reduction in transfusion burden for thalassemia patients.

Speaker Change: So we haven't.

Speaker Change: <unk> spoken in detail about the powering assumption underlying the number but we of course have leveraged all information available to make sure that we have very good statistical justification for this trial and feel confident in the primary endpoint in the sample size that we have selected the primary endpoint by itself as you know is a 50% reduction in <unk>.

Speaker Change: 12 week Rolling period, which we believe can provide very meaningful assessment of the reduction in transfusion burden.

Speaker Change: For thalassemia patients.

Sarah Gheuens: And then just quickly as a follow-up, for AD946, can we still expect to see the full data from the phase 2a trial sometime this year? So we haven't spoken about when we are going to release the Phase 2a data, as the team is assessing the best opportunity on when to do so and the best conference, also in line with when we are getting the Phase 2b up and running. So very focused on that, very excited. We have a milestone around Phase 2b for this year, and so we're on track to deliver that.

Speaker Change: Got it and then just quickly as a follow up for that for Indian Encore six can we still expect to see the full data from the phase two <unk> trial.

Speaker Change: And sometime this year.

Speaker Change: So we haven't spoken about when we are going to release the phase Iia data our asset team is assessing the best the best opportunity to do so in the best Conference.

Speaker Change: Also in line of when we are.

Speaker Change: Getting the phase to be up and running so very focused on that very excited we have a milestone around the phase II b for this year and so we're on track to deliver that.

Speaker Change: Okay. Thank you.

Eric Thomas Schmidt: And our next question comes from the line of Eric Schmidt with Cantor. Your line is now open.

Speaker Change: Thank you.

Speaker Change: And our next question comes from the line of Eric Smith with Cantor. Your line is now open.

Eric Thomas Schmidt: Good morning, everyone. Thanks for taking my question, and congrats on all the progress. Maybe just two quick ones.

Eric Thomas Schmidt: Good morning, everyone. Thanks for taking my question and congrats on all the progress maybe just two quick ones first for Brian and Sarah on this so lets see the pilot can.

Eric Thomas Schmidt: Can you confirm whether it's M.

Eric Thomas Schmidt: The first question for Brian and Sarah on this thalassemia filing: one, I guess, can you confirm whether it's going to be an NDA filing? It sounds like you're already preparing that filing. Just to be very specific, if for some reason the TDP study falls short, you would still be filing for non-transfusion-dependent patients, is that correct?

Speaker Change: <unk> filing.

Eric Thomas Schmidt: Sounds like Youre already preparing that filing.

Eric Thomas Schmidt: Just to be very specific for some reason.

Eric Thomas Schmidt: TVT study fall short, we would still be filing towards non transfusion dependent patients is that correct.

Sarah Gheuens: So, thanks for the question. So our goal is to file the two studies together. As you know, we already have the first part of the data. So, indeed, our filing preparations are completely underway.

Eric Thomas Schmidt: So so.

Speaker Change: So thanks for the question. So our goal is to file the two studies together.

Speaker Change: We have already the first part of the data. So indeed, our filing preparations are completely underway.

Sarah Gheuens: And now we're waiting for that second study. So the fact is that we already have great data for two-thirds of the patient population. So we, of course, want the second study to deliver and make it The Great Story.

Speaker Change: And the team is on track to deliver.

Speaker Change: And now we're waiting for that second study. So the fact is that we already have great data for two thirds of the patient population. So we of course once the second study to deliver.

Speaker Change: And make it.

Speaker Change: No it's a great story.

Sarah Gheuens: If the study falls short, then it truly depends on what the data would show, how we would approach that. But our intent is to file for all thalassemia patients and get that brought.

Speaker Change: If the study would fall short and it truly depends on what.

Speaker Change: What the data would show how we would approach that but our intent is to file for all policy net patients.

Speaker Change: And get that broad indications.

Sarah Gheuens: Thanks for the clarification, Sarah. And just a second question on sickle cell phase three. [inaudible] Binary timelines for next year. Thanks.

Speaker Change: Okay. Thanks for the clarification.

Speaker Change: Just a second question on sickle cell phase III.

Speaker Change: WPZ globally can you provide any kind of color on how that's going or any of them.

Speaker Change: What percent of the study is already on board.

Speaker Change: Maybe.

Speaker Change: Binary yes, your timelines for next year. Thanks.

Sarah Gheuens: Sure, so we are very excited about the RiseUp study. Everything is going well, and the team is doing an amazing job getting that study completely up and running, and we are on track with our enrollment, and so we are completely expecting to be able to deliver towards full enrollment towards the end of this year. We do not guide to specific numbers expected in specific weeks or months. These things are very rapidly changing in big phase 3 trials, so we guide towards bigger milestones.

Binary: Sure. So we are very excited about the rise of study everything is going well and the team is doing an amazing job.

Binary: Getting that study completely up and running and we are on track with our enrollment and so are completely expecting to be able to deliver towards full enrollment towards the end of this year.

Binary: Do not guide to.

Binary: Specific numbers expected in specific.

Binary: Weeks or months. These things are very rapidly changing in big phase III trial, So the guide towards bigger milestones.

Eric Thomas Schmidt: Thanks very much. Congratulations again. Thanks a lot.

Speaker Change: Thanks, very much congrats again.

Alec Stranahan: Our next question will come from the line of Alec Stranahan with Bank of America. Your line is now open.

Binary: Thanks, a lot Eric. Thank you. Our next question will come from the line of Alec Stranahan with Bank of America. Your line is now open.

Alec Stranahan: Hey guys, thanks for taking our questions. We have just a couple from us. First, a commercial question. Assuming both transfusion and non-transfusion end up on the label, any reason to think you'd need to maybe tailor your sales strategy differently between these two patient groups, or will it be more or less the same given they're likely seeing the same prescribers? And then I've got a follow-up.

Alec Stranahan: Hey, guys. Thanks for taking our question just a couple from us.

Alec Stranahan: First a commercial question.

Alec Stranahan: Assuming both transfusion in the non transfusion end up on the label any reason to think you'd need to maybe tailor your sales strategy differently between these two patient groups or will it be more or less the same given that like we've seen the same prescribers and then I've got a follow up.

Brian M. Goff: Sure. Thanks, Alec, and welcome to the Agios call and study. You want to start off?

Speaker Change: Sure Thanks, Alex and welcome to the <unk> call study you want to start off.

Tsveta Milanova: Absolutely, we are super excited to see the positive data from the ENERGIZE study, and as I said, we are eagerly awaiting the data from the ENERGIZE team as well. In terms of launch preparation, we are actively in a LAMP launch preparation mode.

Speaker Change: Absolutely we are super excited with the positive data from the start and as I said, we are eagerly awaiting the data from the energized T as well.

Tsveta Milanova: We believe that there is a high unmet need across both patient populations, transfusion-dependent and non-transfusion-dependent. We have a lot of data that we basically base our launch preparation strategy on, including claims data, the availability of ICD-10 codes, and we basically plan to approach both patient populations in the same way because of the same underlying pathophysiology of the disease, the connection between the two patient populations, and, as you said, the overlap in the prescriber base.

Speaker Change: In terms of the launch preparation we are actively in the last launch preparation mode. We believe that there is a high unmet need across that broad patient populations in our student dependent and non transfusion dependent.

Speaker Change: We have a lot of data that we are basically our launch preparation strategy in closing claims data availability of ICD 10 codes.

Speaker Change: We are basically plateau approach.

Speaker Change: The same way both patient populations because of the.

Speaker Change: Same underlying pathophysiology of the disease the connection between the two patient populations and as you said the overlap in the prescriber base of course, you'll see a little bit more fun for information and the non transfusion dependent patients in the kols.

Tsveta Milanova: Of course, you see a little bit more concentration of non-confusion-dependent patients in the care well and centers of excellence setting and a bit more of the non-confusion-dependence in the community setting, but that would not change the approach of deployment, communication, and education.

Speaker Change: Excellent setting in a bit more of.

Speaker Change: The non transfusion dependency in the community setting, but that it would not change the approach of deployment and communication and education.

Brian M. Goff: The only thing I would add is that with the transfusion-dependent patients, there's obviously more regularity in clinician visits than you tend to see with the non-transfusion-dependent patients. But I'm really proud of the fact that Sveta and the team are prepared for all scenarios.

Speaker Change: The only thing I would add is that with the transfusion dependent patients theres, obviously more regularity of clinician visits.

Speaker Change: You tend to see with the non transfusion dependent patients, but I'm really proud of the fact that instead of the team.

Alec Stranahan: Okay, perfect. And then just one question on the ex-U.S. opportunity. I know you've said that the plan would likely be to partner in ex-U.S. geographies, but any additional color you can provide around, you know, timing or or scope of the XUS opportunity, just from a modeling perspective for us. Thank you.

Speaker Change: Prepared for all scenarios.

Speaker Change: Okay perfect.

Speaker Change: And then just one question on the ex U S opportunity I know you've said that the.

Speaker Change: The plan would likely be to partner ex U S geographies, but.

Speaker Change: Any additional color you can provide around timing or scope of the ex U S opportunity just from a modeling perspective for us. Thank you.

Tsveta Milanova: Absolutely. So, in addition to actively preparing for launch in the U.S., we are also actively searching for the best possible partner for us to maximize the ex-U.S. opportunity. We've mentioned on several occasions that the Gulf region is a high priority for us, given that there are 70,000 patients with thalassemia in that region. Sarah and the team are preparing for regulatory submissions in these regions actively as well, to submit as quickly as possible, so that that will allow us.

Speaker Change: Absolutely still in addition talk actively preparing for launch in the U S.

Speaker Change: We're also actively searching for the best possible partner for us to maximize the ex U S opportunity. We've mentioned on several occasions that the Gulf region is a high priority for us given that they are 70000 patients with the lithemia.

Speaker Change: That region, Sarah and the team are preparing for regulatory submissions in these regions actively as well submit as quickly as possible that that will allow us.

Tsveta Milanova: And we'll provide updates as soon as we have a progressive discussion and identify the partner. But we are in a very strong position, especially now with the positive data from ENERGYSE, to have a very high-quality discussion with partners who have strong expertise in the region. We are excited about it because our clinical studies are also done in the region, and there is a lot of care well advocacy and experience with thalassemia and metaphylaxis. So, equally an exciting place as the U.S. launch as well.

Speaker Change: And we will provide update as soon as we have a progressive discussion I mean densify the partner, but we already have very strong position, especially now with the positive data from <unk>, you'll have a very high quality discussions with partners. We will have strong expertise in the region.

Speaker Change: We are excited about it because our clinical studies are also down in the region and there is a lot of.

Speaker Change: Advocacy on experience.

Speaker Change: With the lifting of make up their lifestyle equally an exciting place, though as the U S market as well.

Operator: Great, thanks again for the question. Thank you all.

Speaker Change: Great. Thanks again for the question.

Speaker Change: Thank you.

Tessa Thomas Romero: Our next question comes from the line of Tess Romero with J.P. Morgan. Your line is now open.

Speaker Change: You.

Speaker Change: Our next question comes from the line of Tess Romero with Jpmorgan. Your line is now open.

Tessa Thomas Romero: Hi, good morning, Brian and team. Thanks so much for taking our question, Cecilia here.

Tessa Thomas Romero: Hi, good morning, Brian and team. Thanks, so much for taking our question.

Cecilia Jones: I'm just curious, can you walk us through the pushes and pulls on your balance sheet and how you think about means to potentially extend that runway and what your latest thinking is there? We noticed you included in your release today. How interested specifically are you in potentially a royalty monetization for Rora Sidonib? And then on the partnering side outside of the U.S., just to clarify Sveta's comment here, could that happen this year?

Tessa Thomas Romero: Sure.

Tessa Thomas Romero: First is the only here.

Tessa Thomas Romero: Just curious can you walk us through the <unk>.

Tessa Thomas Romero: And polls on your balance sheet, and how you think about it.

Tessa Thomas Romero: I mean could potentially extend that runway and what your latest thinking there.

Tessa Thomas Romero: We noticed you including in your release today.

Speaker Change: Thank you.

Speaker Change: Are you and potentially.

Speaker Change: Royalty monetization for more aside and add on and then on the partnering side outside of the U S. Just to clarify that comment here.

Speaker Change: Did that occur this year. Thanks.

Cecilia Jones: Thanks. Thanks, Tessa. I'm going to start, and we can add on the text you have too.

Cecilia Jones: Thanks, Tessa. I'll get started, and we can add the next few as well. So yes, we have guided that we will have our cash at least into 2026. We purposely left out a couple of things that you mentioned, so I'll cover some of those. But there are other things, like we obviously continue to manage our cost basis thoughtfully and in a disciplined way. We are now starting to prepare for the launch, but we waited to make sure we had the data before we went ahead with that. On the Vora side.

Speaker Change: Thanks, Doug.

Speaker Change: On the access to them.

Speaker Change: So yes.

Sarah Gheuens: We have guided that we have cash at least into 2026, and we purposely left out a couple of things that you mentioned, so I'll cover some of those but theres other things like we obviously continue to manage our cost base it thoughtfully and in a disciplined way. We now are starting to prepare for the launch but we waited.

Sarah Gheuens: To make sure we had the data before we went ahead with that on the voice side.

Cecilia Jones: That's another option that we looked at as we evaluated to extend our runway. In the prepared remarks, the survey publicly announced that the FDA accepted their filing, and they have a PDUFA date on August 20th. And as a reminder, we have a $200 million milestone on FDA approval and 15% royalties on U.S. net sales for that. And we will evaluate opportunities to sell that, the whole amount or a portion of that, as part of our way to extend the runway as we do with other things. The other option or the other piece that we left out, as you mentioned, is the ex-U.S. portion. That can come in different shapes and forms, and that's part of the reason we left it out.

Alec Stranahan: That's another option that we looked as we evaluate two to extend our runway we I see that we had in the prepared remarks, the Soviets publicly announced that the FDA accepted our filing and they have a video for date on August 20th and as a reminder, we have a 200 million dollar milestone and FDA approval and 15% at royalties on <unk>.

Cecilia Jones: <unk> net sales for that and we will evaluate opportunities to sell is that the whole amount of our portion of that in spite of a way to extend the runway as we linked in with other things the other option or the other piece that we left out as you mentioned is the ex U S.

Cecilia Jones: Portion that can come in different shapes and forms and thats part of the reason we left it out that timing obviously the teams are working to make sure we have.

Cecilia Jones: The timing, obviously, the teams are working to make sure we have the best partners and that is reflective of where the patients are, as Tsveta described. And we want to try to do that as fast as possible to get access to those patients. Thank you. And then next.

Cecilia Jones: The best partner and that is reflective of where the patients are like I said I described and we wanted to try to do that as fast as possible to get access to those patients.

Speaker Change: Thank you.

Cecilia Jones: Okay.

Operator: And our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Speaker Change: Thank you.

Victor Salvino: And our next question comes from the line of Salvino, Victor with Goldman Sachs. Your line is now open.

Salveen Jaswal Richter: Hi, This is <unk> on for Sylvia and thanks, so much for taking our question just on the upcoming energize key readout could you just discuss the clinical bar for success here and what you're hoping to see in terms of the percentage of patients with a reduction in transfusion burden.

Salveen Jaswal Richter: Should we expect this readout to kind of take a similar form to the earlier energize readouts. Thank so much.

Salveen Jaswal Richter: Thanks for the question. So, in regards to the NRGIS-T readout, of course, we're hoping to hit on our primary endpoint of a 50% reduction in any 12-week rolling period. We have not spoken about the exact difference we are shooting for between placebo and mid-top eval, but... In regards to the trial itself, it is, of course, well-designed to be able to hit on a primary endpoint with the assumptions that are underpinning that design.

Salveen Jaswal Richter: Thanks for the question so for in regards to the energized readout of course, we're hoping to hit on a primary endpoint with a reduction of 50% reduction any 12 week rolling period.

Salveen Jaswal Richter: We have not spoken about the exact difference we are shooting for between placebo or and Metopic Bob but.

Salveen Jaswal Richter: In regards to <unk>.

Salveen Jaswal Richter: The trial itself. It is of course, well designed to be able to hit on the primary endpoint with the assumptions that are underpinning that design.

Salveen Jaswal Richter: What we know, though, is that the clinical trial bar of what we're shooting for that 50% reduction, but in the real world, we know that the bar actually may be lower because what the product would do is basically remove some of the clinic visits for patients if they can skip transfusions, and that would have a big impact on quality of life for transfusion-dependent thalassemia patients. I think Tsveta can maybe add a little bit to what we expect from the real world.

Salveen Jaswal Richter: Well, we know though is there is the clinical trial bar of what we're shooting for about 50% reduction but.

Salveen Jaswal Richter: But in the real World, we know that the bar actually may be lower because.

Tsveta Milanova: What about the product would do is basically bring.

Salveen Jaswal Richter: Move some of the clinic visits for patients if they can skip transfusions and that would have a big impact on quality of life for transfusion dependent thalassemia patients I think set I can maybe add a little bit.

Sarah Gheuens: Absolutely. You mentioned it, Sarah.

Tsveta Milanova: On what we expect for the real World.

Tsveta Milanova: You mentioned the clinical bar is obviously very important from a regulatory perspective, but in one way here both from patients.

Tsveta Milanova: In terms of utilization there'll be looking for the right deals up in our future.

Tsveta Milanova: Even at the lower rate of sale proceeds are best clinically meaningful because even extending that non fusion kind of frequency by a week on a patient basis is very meaningful on actually health care system basis, as well and finish up with it is very meaningful.

Tsveta Milanova: The clinical bar is obviously very important from a regulatory perspective, but what we hear both from patients and clinicians in terms of utilization, they'll be looking to reduce the transfusion burden, even at the lower rate, and they'll consider that clinically meaningful because even extending the transfusion kind of frequency by a week on a patient basis is very meaningful on a, actually, healthcare system basis as well. It is very meaningful. So we're super excited to see the data and actively getting ready for launch. And I'll just add maybe one last comment, which is that

Tsveta Milanova: Super excited next door and wait to see the data getting ready actively for lunch.

Brian M. Goff: And I'll just add maybe one last comment, which is that obviously we're going for statistical significance in the ENERGIZE-T study. From past experience, we know that there could be the temptation for cross-study comparisons as well. And I just want to emphasize that the compelling totality of the profile of midipivat means we don't necessarily need numerical equivalence.

Tsveta Milanova: And I'll just add maybe one last comment which is that obviously, we're going for statistical significance in the <unk> T study.

Brian M. Goff: From past experience, we know that there could be the temptation for cross study comparisons as well.

Brian M. Goff: I want to emphasize that the.

Brian M. Goff: The compelling totality of the profile look me to pivot. It means we don't necessarily need numerical equivalents, what we need is statistical significance from the endpoint, that's what we're targeting but the fact that this is an oral therapy means the patients are already in a way free of the clinic relative to.

Brian M. Goff: What we need is statistical significance from the endpoint. That's what we're targeting. But the fact that this is an oral therapy means the patients are already in a way free of the clinic relative to other alternatives, i.e., lispatercept. And we see that, on top of all else, that's another real advantage at the patient level.

Brian M. Goff: Other alternatives <unk> Patterson.

Brian M. Goff: And we see that is on top of all else. That's another real advantage at the patient level.

Speaker Change: Thanks, so much.

Operator: Thank you. And our last question will come from the line of Danielle Brill with Raymond James. Your line is now open.

Speaker Change: Youre welcome.

Speaker Change: Thank you Andrew.

Operator: And our last question will come from the line of Danielle Brill with Raymond James Your line is now open.

Danielle Brill: Hi guys, good morning. Thanks so much for taking the time to answer my questions. First, I wanted to ask a question about the expected placebo response for Energize T. In Ms. Patersep's trial, I believe the placebo response rate as you defined it for your primary was around 6%. I would like to know your thoughts on how the placebo population is able to achieve that level of reduction, and are you expecting a similar outcome with Energize T? And then, as a quick follow-up, I'm just curious how you plan to announce the data. Will this be a top-line PR, or is it possible that you'll present it at EHA? Thank you.

Danielle Brill: Hey, guys. Good morning, Thanks, so much for taking my questions.

Danielle Brill: First I wanted to ask a question about the expected placebo response for <unk> T.

Danielle Brill: And with patterns that's trial I believe the placebo response rate as you defined it for your primary was around 6% curious your thoughts on how the placebo population is able to achieve that level of reduction and are you expecting a similar outcome in <unk> and then as a quick follow up I'm just curious how you plan to announce it.

Danielle Brill: Data will just be a topline PR or is it possible that you will pay.

Danielle Brill: Presented at Aha. Thank you.

Sarah Gheuens: Thanks. Yeah, so there's always fluctuation when you measure transfusions. So 6% for the placebo in regards to the primary endpoint definition is a very reasonable observation. And that is also because, in clinical practice, sometimes patients get transfused based on symptom presence and things like that. In regards to how we are going to announce the data, yes, we typically do a top-line release via press release. We will not be able to present data at EHA because the timeframe for submission of data there is long gone, so that is not in the plan.

Danielle Brill: I understand. Thanks so much.

Speaker Change: Thanks, Yeah, So theres always fluctuation when you measure transfusions was 6% for the placebo.

Danielle Brill: In regard to the as the primary endpoint definition is is a very reasonable.

Danielle Brill: Officer patients.

Danielle Brill:

Danielle Brill: And that is also because in clinical practice, sometimes patients gets transfused.

Danielle Brill: Based on system presence and things like that so.

Danielle Brill: In regards to how we are going to announce the data yes, we typically do to a top line release of the press release.

Danielle Brill: We will not be able to present data at <unk>.

Danielle Brill: Timeframe for submission of data there is long gone so that will that is not in the plants.

Speaker Change: Understood. Thanks, so much.

Speaker Change: Thank you.

Operator: And that concludes today's question and answer session. I'll now turn the call back to Brian Goff for his closing remarks.

Speaker Change: Thank you Andrew.

Danielle Brill: And this concludes today's question and answer session I will now turn the call back to Brian golf for closing remarks.

Brian M. Goff: Thanks a lot, Norma, and thank you very much, everyone, for participating in today's call. I hope this is clear. It's a very exciting time at Agios. We believe that we are well-poised to deliver transformative new therapies for patients as well as create significant long-term value for shareholders. So thanks again, and we look forward to speaking with all of you again soon.

Speaker Change: Thanks, a lot Norma and thank you very much everyone for participating in today's call I think I hope it's clear it's a very exciting time at <unk>, we believe that we're <unk>.

Brian M. Goff: Well poised to deliver transformative new therapies for patients as well as creating significant long term value to shareholders. So thanks again, and we look forward to speaking with all of you again soon.

Operator: This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.

Operator: This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.

Operator: Okay.

Operator: [music].

Operator: Okay.

Operator: [music].

Operator: <unk>.

Operator: Yes.

Operator: [music].

Operator: Sure.

Operator: [music].

Operator: Yes.

Operator: [music].