Q2 2025 Agios Pharmaceuticals Inc Earnings Call

July 31, 2025

Operator: Good morning, welcome to Agios Q2 2025 Conference Call. At this time, all participants are in a listen-only mode. There will be a question and answer session at the end. Please be advised that this call is being recorded at Agios request. I would now like to turn the call over to Agios. Please go ahead.

Operator: Good morning and welcome to Agios Pharmaceuticals' second quarter 2025 conference call. At this time, all participants are in a listen-only mode. There will be a question and answer session at the end. Please be advised that this call is being recorded at Agios Pharmaceuticals' request. I would now like to turn the call over to Agios Pharmaceuticals. Please go ahead.

Okay.

Good morning, and welcome to <unk> second quarter 2025 conference call. At this time all participants are in a listen only mode. There will be a question and answer session. At the end. Please be advised that this call is being recorded and at yours request I would now like to turn the call over to Archie. Please go ahead.

Morgan Sanford: Thank you, operator. Good morning, everyone. I'm Morgan Sanford, Vice President of Investor Relations at Agios. Thank you for joining us to discuss Agios Pharmaceuticals' Q2 2025 financial results and business highlights. You can access the slides for today's call by going to the investor section of our website, agios.com. Please move to the next slide. Today, we'll be making certain forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statement. Because of various risks, uncertainties, 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. Next slide, please. On the call with me today from Agios are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; Tsveta Milanova, Chief Commercial Officer; and Dr.

Morgan Sanford: Thank you, operator. Good morning, everyone. I am Morgan Sanford, Vice President of Investor Relations at Agios Pharmaceuticals. Thank you for joining us to discuss Agios Pharmaceuticals' second quarter 2025 financial results and business highlights. You can access the slides for today's call by going to the Investor section of our website, agios.com. Please move to the next slide. Today, we will be making certain forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statement because of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. Next slide, please. On the call with me today from Agios Pharmaceuticals are Brian Goff, Chief Executive Officer; Cecilia Jones, Chief Financial Officer; Tsveta Milanova, Chief Commercial Officer; and Dr.

Thank you operator, good morning, everyone I'm Morgan, Stanford Vice President of Investor Relations that aren't yet.

Thank you for joining us to discuss our jazz Pharmaceuticals second quarter 2025 financial results indexes highlight you can access the slides for today's call by going to the investors section of our website at <unk> Dot com.

Please move to the next slide today, we'll be making certain forward looking statements actual events and results could differ materially from those expressed or implied by any forward looking statements.

Because of various risks uncertainties and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC.

Next slide please.

On the call with me today from <unk> are Brian Goff, Chief Executive Officer.

Morgan Sanford: Sarah Gheuens, Chief Medical Officer and Head of Research and Development. Following prepared remarks, we will open the call for questions. With that, please move to the next slide, and I am pleased to turn the call over to Brian.

Julia Jones, Chief Financial Officer.

One of our Chief commercial officer, and Dr. Sarah <unk>, Chief Medical Officer, and head of research and development. Following prepared remarks, we will open the call for questions with that things move to the next slide and I'm pleased to turn the call over to Brian.

Brian Goff: Thanks, Morgan. Good morning, everyone, and thank you for joining us on today's call. Next slide, please. 2025 is shaping up to be a breakout year for Agios, and we believe we have a clear path to deliver sustainable growth and unlock long-term shareholder value. First, we have a de-risked multi-billion-dollar opportunity with our first-in-class PK activator, PYRUKYND. Second, momentum is building as we approach multiple near-term high-value catalysts. We hope to add thalassemia as the second approved indication for PYRUKYND in the US, pending FDA approval, and we are now less than 40 days from our September 7 PDUFA goal date.

Brian Goff: Thanks, Morgan. Good morning, everyone, and thank you for joining us on today's call. Next slide, please. 2025 is shaping up to be a breakout year for Agios Pharmaceuticals, and we believe we have a clear path to deliver sustainable growth and unlock long-term shareholder value. First, we have a de-risked multi-billion dollar opportunity with our first-in-class PK activator, Pyrukynd. Second, momentum is building as we approach multiple near-term high-value catalysts. We hope to add thalassemia as the second approved indication for Pyrukynd in the U.S. pending FDA approval, and we are now less than 40 days from our September 7th PDUFA gold date.

Thanks, Morgan Good morning, everyone and thank you for joining us on today's call next slide please.

2025 is shaping up to be a breakout year for our Geos and we believe we have a clear path to deliver sustainable growth and unlock long term shareholder value.

We have a derisked multibillion dollar opportunity with their first in class PK activator pirate time.

Second momentum is building as we approach multiple near term high value catalyst.

We hope to add thalassemia as the second approved indication for pirate kind in the U S. Pending FDA approval and we are now less than 40 days from our September 7th could do for gold date.

Brian Goff: We expect to read out the RISE UP Phase 3 trial for Pyrukynd in sickle cell disease before the end of the year, and early next year anticipate Phase 2B data for tebapivat, our more potent PK activator, in patients with anemia due to lower risk myelodysplastic syndromes. Third, we are well capitalized to develop and launch Pyrukynd in thalassemia and sickle cell disease and to continue to advance our existing development programs, as well as look opportunistically to expand our pipeline through internal efforts and business development activities. Please move to the next slide. In the second quarter, we reported $12.5 million in net revenue, reflecting the strong value proposition of Pyrukynd. We entered into an agreement with Advansanite Bioscience to commercialize and distribute Pyrukynd in Europe. This is a capital-efficient deal, allowing us to focus our investment on commercial launches in the U.S.

Brian Goff: We expect to read out the RISE UP Phase 3 trial for Pyrukynd in sickle cell disease before the end of the year, and early next year anticipate Phase 2B data for Tebepivat, our more potent PK activator, in patients with anemia due to lower risk myelodysplastic syndromes. Third, we are well capitalized to develop and launch Pyrukynd in thalassemia and sickle cell disease and to continue to advance our existing development programs, as well as look opportunistically to expand our pipeline through internal efforts and business development activities. Please move to the next slide. In the second quarter, we reported $12.5 million in net revenue, reflecting the strong value proposition of Pyrukynd. We entered into an agreement with Advansanite Bioscience to commercialize and distribute Pyrukynd in Europe. This is a capital-efficient deal, allowing us to focus our investment on commercial launches in the U.S.

Brian Goff: We expect to read out the RISE UP Phase 3 trial for PYRUKYND in sickle cell disease before the end of the year, and early next year anticipate Phase 2B data for tebapivat, our more potent PK activator in patients with anemia due to lower risk myelodysplastic syndromes. Third, we are well-capitalized to develop and launch PYRUKYND in thalassemia and sickle cell disease and to continue to advance our existing development programs, as well as look opportunistically to expand our pipeline through internal efforts and business development activities. Please move to the next slide. In Q2, we reported $12.5 million in net revenue, reflecting the strong value proposition of PYRUKYND. We entered into an agreement with Avanzanite Bioscience to commercialize and distribute PYRUKYND in Europe. This is a capital-efficient deal, allowing us to focus our investment on commercial launches in the US.

We expect to read out the rise up phase III trial for pirate kind in sickle cell disease before the end of the year and early next year anticipate phase <unk> data for Teva pivot are more potent PK activator in patients with anemia due to lower risk Myelodysplastic syndromes.

And third we are well capitalized to develop and launch pirate kind in thalassemia and sickle cell disease and to continue to advance our existing development programs as well as look opportunistically to expand our pipeline through internal efforts and business development activities.

Please move to the next slide.

In the second quarter, we reported $12 5 million and net revenue, reflecting the strong value proposition of pirate time.

We entered into an agreement with <unk> bioscience to commercialize and distribute pirate kind in Europe.

Brian Goff: We exited the second quarter with approximately $1.3 billion in cash, cash equivalents, and marketable securities, and intend to be disciplined in our investment behind the commercial build-out of Pyrukynd and advancement of our pipeline. In the second quarter, we dosed the first patient in the Phase 2 trial of tebapivat in sickle cell disease and received IMD clearance for AG-236, our siRNA targeting TEMPER6, intended for the treatment of polycythemia vera. We are at an important turning point in our growth story. Near term, we have the potential to transform the treatment of thalassemia and sickle cell disease with Pyrukynd, and beyond, we have the opportunity to deliver additional medicines to rare disease patients waiting and in urgent need of innovative treatment options.

Brian Goff: We exited the second quarter with approximately $1.3 billion in cash, cash equivalents, and marketable securities, and intend to be disciplined in our investment behind the commercial build-out of Pyrukynd and advancement of our pipeline. In the second quarter, we dosed the first patient in the Phase 2 trial of Tebepivat in sickle cell disease and received IMD clearance for AG-236, our siRNA targeting TEMPER6, intended for the treatment of polycythemia vera. We are at an important turning point in our growth story. Near term, we have the potential to transform the treatment of thalassemia and sickle cell disease with Pyrukynd, and beyond, we have the opportunity to deliver additional medicines to rare disease patients waiting and in urgent need of innovative treatment options.

Brian Goff: We exited Q2 with approximately $1.3 billion in cash equivalents, and marketable securities intend to be disciplined in our investment behind the commercial build-out of PYRUKYND and advancement of our pipeline. In Q2, we dosed the first patient in the phase 2 trial of tebapivat in sickle cell disease received IND clearance for AG-236, our siRNA targeting TMPRSS6, intended for the treatment of polycythemia vera. We are at an important turning point in our growth story. Near term, we have the potential to transform the treatment of thalassemia and sickle cell disease with PYRUKYND. Beyond, we have the opportunity to deliver additional medicines to rare disease patients waiting and in urgent need of innovative treatment options.

This is a capital efficient deal, allowing us to focus our investment on commercial launches in the U S.

We exited the second quarter was approximately $1 $3 billion in cash cash equivalents and marketable securities and intend to be disciplined in our investment behind the commercial build out of pirate time and advancement of our pipeline.

In the second quarter, we dosed the first patient in the phase II trial of <unk> in sickle cell disease and.

And received IND clearance for AG 203, six Rsi RNA targeting Tempur six intended for the treatment of Polycythemia Bureau.

We are at an important turning point in our growth story.

Near term, we have the potential to transform the treatment of thalassemia and sickle cell disease with pirate time and beyond we have the opportunity to deliver additional medicines to rare disease patients waiting and in urgent need of innovative treatment options.

Brian Goff: Please move to the next slide, and I'll turn the call over to Cecilia to provide additional commentary on our second quarter performance and the future trajectory for Pyrukynd.

Brian Goff: Please move to the next slide. I'll turn the call over to Cecilia to provide additional commentary on our Q2 performance and the future trajectory for PYRUKYND.

Please move to the next slide and I will turn the call over to Cecilia to provide additional commentary on our second quarter performance and the future trajectory for powertrain.

Cecilia Jones: Thank you, Brian. Next slide, please. Our Q2 2025 financial results can be found in the press release issued earlier this morning, additional details can be found in our 10-Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Q2 net PYRUKYND revenue was $12.5 million, an increase of 45% compared to $8.6 million in Q2 2024, an increase of 44% compared to $8.7 million in Q1 2025. Sequential net revenue growth reflects continued commercial execution in PKD, as well as an extra week of ordering in Q2 and an increase in the number of units processed directly by the specialty pharmacy.

Cecilia Jones: Thank you, Brian. Next slide, please. Our second quarter 2025 financial results can be found in the press release issued earlier this morning, and additional details can be found in our 10-Q, which will be filed later today. Let me now take a moment to provide some context and highlight a few key points. Second quarter net Pyrukynd revenue was $12.5 million, an increase of 45% compared to $8.6 million in the second quarter of 2024, and an increase of 44% compared to $8.7 million in the first quarter of 2025. Sequential net revenue growth reflects continued commercial execution in PKD, as well as an extra week of ordering in the second quarter and an increase in the number of units processed directly by the specialty pharmacy. In the second half of the year, we expect continued quarter-on-quarter variability in net revenues due to ordering patterns.

Thank you Bryan next slide please our second quarter 2025 financial results can be found in the press release issued earlier. This morning, and additional details can be found in our 10-Q, which will be filed later today.

We will now take a moment to provide some context and highlight a few key points.

Second quarter net financing revenue was $12 $5 million, an increase of 45% compared to $8 $6 million in the second quarter of 2024, and then increase of 44% compared to $8 $7 million in the first quarter of 2025.

Sequential net revenue growth reflects continued commercial execution in PK D as well as an extra week of ordering in the second quarter and in increasing the number of units processed directly by the specialty pharmacy.

Cecilia Jones: In the second half of the year, we expect continued quarter-on-quarter variability in net revenues due to ordering patterns. Pending approval for thalassemia in the US, we expect softer PKD demand as the sales force transitions promotional focus to thalassemia. We still anticipate the Q4 to reflect partial demand for thalassemia given timing of our PDUFA goal date due to the expected time to convert patient enrollment forms to treatment initiation. Taken together, on a full-year basis across indications, we expect net revenues in 2025 to show modest growth compared to 2024. Cost of sales for the quarter was $1.7 million. R&D expenses were $91.9 million, an increase of $14.5 million compared to the Q2 2024.

Cecilia Jones: Pending approval for thalassemia in the U.S., we expect softer PKD demand as the salesforce transitions promotional focus to thalassemia. We still anticipate the fourth quarter to reflect partial demand for thalassemia, given timing of a PDUFA goal date due to the expected time to convert patient enrollment forms to treatment initiation. Taken together, on a full-year basis across indications, we expect net revenues in 2025 to show modest growth compared to 2024. Cost of sales for the quarter was $1.7 million. R&D expenses were $91.9 million, an increase of $14.5 million compared to the second quarter of 2024. This increase was primarily driven by a $10 million milestone payment to our partner, Alnilam, related to the development of AG-236.

In the second half of the year, we expect continued quarter over quarter variability in net revenues due to ordering patterns.

Pending approval for thalassemia in the U S. We expect softer PTC demand at the sales force transitions promotional focus to <unk>.

We still anticipate the fourth quarter to reflect question demand for select cement given timing of Purdue football eight due to the expected time to convert patient enrollment forms to treatment initiation.

Taken together on a full year basis across indications, we expect net revenues in 2025 to show modest growth compared to 2024.

Cost of sales for the quarter was $1 $7 million.

R&D expenses were $91 $9 million, an increase of $14 $5 million compared to the second quarter of 2024.

Cecilia Jones: This increase was primarily driven by a $10 million milestone payment to our partner, Alnylam, related to the development of AG-236. SG&A expenses were $45.9 million in Q2, an increase of $10.4 million compared to the prior year, driven by continued investment ahead of the potential commercial launch of PYRUKYND for the treatment of thalassemia. We ended Q2 with cash equivalents, and marketable securities of approximately $1.3 billion. Next slide, please. Our strong balance sheet supports our focused capital allocation strategy, allowing us to invest in our next wave of growth and pipeline delivery. First, we have executed a capital-efficient commercial build-out, prioritizing investment in potential US launches, which presents the largest commercial opportunity.

This increase was primarily driven by a $10 million milestone payment to our partner asylum related to the development of AG 286.

Cecilia Jones: SG&A expenses were $45.9 million in the second quarter, an increase of $10.4 million compared to the prior year, driven by continued investment ahead of the potential commercial launch of Pyrukynd for the treatment of thalassemia. We ended the second quarter with cash, cash equivalents, and marketable securities of approximately $1.3 billion. Next slide, please. Our strong balance sheet supports our focused capital allocation strategy, allowing us to invest in our next wave of growth and pipeline delivery. First, we have executed a capital-efficient commercial build-out, prioritizing investment in potential U.S. launches, which presents the largest commercial opportunity. Last year, we announced our partnership with Newbridge Pharmaceuticals to commercialize Pyrukynd in the GCC, and last month, we entered into an agreement with Advansanite Bioscience to commercialize and distribute Pyrukynd in Europe. Both agreements are structured as revenue-sharing arrangements that favor Agios Pharmaceuticals over the long term.

SG&A expenses were $45 $9 million in the second quarter, an increase of $10 $4 million compared to the prior year driven by continued investment ahead of the potential commercial launch of pilot kind of for the treatment of thalassemia.

We ended the second quarter with cash cash equivalents in marketable securities of approximately $1 $3 billion.

Next slide please.

Our strong balance sheet supports our focused capital allocation strategy, allowing us to invest in our next wave of growth and pipeline deliveries.

First we have executed our capital efficient commercial paper towels, prioritizing investment and potential U S launches, which presents the largest commercial opportunity.

Cecilia Jones: Last year, we announced our partnership with NewBridge Pharmaceuticals to commercialize PYRUKYND in the GCC. Last month, we entered into an agreement with Avanzanite Bioscience to commercialize and distribute PYRUKYND in Europe. Both agreements are structured as revenue-sharing arrangements that favor Agios over the long term. We will record our share of ex-US sales as net revenues. Second, we are strategically investing in our pipeline to advance our early and mid-stage clinical programs. Third, we will opportunistically look for ways to expand our pipeline through internal efforts or externally sourced assets. In closing, I am confident that our balance sheet will enable us to continue to execute from a position of strength. Please advance to the next slide. I will turn the call over to Sveta to share commercial highlights for the quarter.

Last year, we announced our partnership with Newbridge Pharmaceuticals to commercialize <unk> in the GCC and last month, we entered into an agreement with advanced Tonight Bioscience to commercialize and distribute part of banks in Europe.

Cecilia Jones: We will record our share of ex-U.S. sales as net revenue. Second, we are strategically investing in our pipeline to advance our early and mid-stage clinical programs. Third, we will opportunistically look for ways to expand our pipeline through internal efforts or externally sourced assets. In closing, I am confident that our balance sheet will enable us to continue to execute from a position of strength. Please advance to the next slide, and I will turn the call over to Tsveta Milanova to share commercial highlights for the quarter.

Both agreements are structured as revenue sharing arrangements that fever Ics over the long term.

We will record our share of ex U S sales of net revenues.

Second we are strategically investing in our pipeline to advance our early and mid stage clinical programs.

Third we will opportunistically look for ways to expand our pipeline through internal efforts or externally sourced asset.

In closing I am confident that our balance sheet will enable us to continue to execute from a position of strength.

Tsveta Milanova: Thank you, Cecilia. Next slide, please. Net revenue growth in Q2 reflects strong execution by our commercial team. However, we continue to anticipate quarter-on-quarter variability due to ordering and inventory dynamics typical for rare disease medicines. As of Q2, 248 patients completed prescription enrollment forms, up 6% from Q1 2025. 142 patients are now on active Pyrukynd treatment, an increase of 4% on a sequential basis. Please move to the next slide. With less than 40 days to our PDUFA goal date, our commercial team is fully prepared for a launch in thalassemia, pending FDA approval. We believe in Pyrukynd's strong clinical profile shown across two phase 3 studies, ENERGIZE in non-transfusion-dependent patients and ENERGIZE-T in transfusion-dependent patients.

Tsveta Milanova: Thank you, Cecilia Jones. Next slide, please. Net revenue growth in the second quarter reflects strong execution by our commercial team. However, we continue to anticipate quarter-on-quarter variability due to ordering and inventory dynamics typical for rare disease medicines. As of the second quarter, 248 patients completed prescription enrollment forms, up 6% from the first quarter of 2025. 142 patients are now on active Pyrukynd treatment, an increase of 4% on a sequential basis. Please move to the next slide. With less than 40 days to our PDUFA goal date, our commercial team is fully prepared for launching thalassemia pending FDA approval. We believe in Pyrukynd's strong clinical profile shown across two Phase 3 studies: ENERGIZE in non-transfusion-dependent patients and ENERGIZE-T in transfusion-dependent patients.

Tsveta Milanova: Thank you, Cecilia. Next slide, please. Net revenue growth in the second quarter reflects strong execution by our commercial team. However, we continue to anticipate quarter-on-quarter variability due to ordering and inventory dynamics typical for rare disease medicines. As of the second quarter, 248 patients completed prescription enrollment forms, up 6% from the first quarter of 2025. 142 patients are now on active Pyrukynd treatment, an increase of 4% on a sequential basis. Please move to the next slide. With less than 40 days to our PDUFA goal date, our commercial team is fully prepared for launching thalassemia, pending FDA approval. We believe in Pyrukynd's strong clinical profile shown across two Phase 3 studies: Energize in non-transfusion-dependent patients and Energize-T in transfusion-dependent patients.

Please advance to the next slide and I will turn the call over to <unk> to share commercial highlights for the quarter.

Thank you Cecilia next slide please.

Net revenue growth in the second quarter reflects strong execution by our commercial team. However, we continue to anticipate quarter on quarter variability.

Ordering and inventory dynamic typical for rare disease medicines.

As of the second quarter 248 patient completed prescription enrolment forums up 6% from the first quarter of 2025.

142 patients are now an active viral client treatment, an increase of 4% on a sequential basis.

Please move to the next slide.

With less than 40 days to our Paducah validates our commercial team is fully prepared for a launch into leukemia pending FDA approval we.

We believe in a viral crime strong clinical profile shown across two phase <unk> study and our Jive in non transfusion dependent patients and and then as I see in transfusion dependent patients.

Tsveta Milanova: As shown on this slide, data generated across this robust clinical program means upon potential approval, we are set to deliver a series of firsts in the treatment of thalassemia in the US, all of which are profoundly meaningful to thalassemia patients. Next slide, please. We are confident in our ability to deliver on the US launch of PYRUKYND in thalassemia, pending FDA approval for several reasons. First, thalassemia is well diagnosed due to widespread prevalence of newborn patient screening in the US. In addition, given the availability of claims data and ICD-10 codes, these patients have an established record of engagement with healthcare services. Second, the burden of disease is high, meaning symptomatic patients are actively managed and the associated cost of care is significant. Despite this, treatment options are limited, especially for patients with non-transfusion-dependent disease, and most patients still rely on supportive therapy.

Tsveta Milanova: As shown on this slide, data generated across this robust clinical program means upon potential approval, we are set to deliver a series of firsts in the treatment of thalassemia in the U.S., all of which are profoundly meaningful to thalassemia patients. Next slide, please. We are confident in our ability to deliver on the U.S. launch of Pyrukynd in thalassemia pending FDA approval for several reasons. First, thalassemia is well diagnosed due to widespread prevalence of newborn patient screening in the U.S. In addition, given the availability of claims data and ICD-10 codes, these patients have an established record of engagement with healthcare services. Second, the burden of disease is high, meaning symptomatic patients are actively managed, and the associated cost of care is significant. Despite this, treatment options are limited, especially for patients with non-transfusion-dependent disease, and most patients still rely on supportive therapy.

Tsveta Milanova: As shown on this slide, data generated across this robust clinical program means upon potential approval, we are set to deliver a series of firsts in the treatment of thalassemia in the U.S., all of which are profoundly meaningful to thalassemia patients. Next slide, please. We are confident in our ability to deliver on the U.S. launch of Pyrukynd in thalassemia, pending FDA approval for several reasons. First, thalassemia is well diagnosed due to widespread prevalence of newborn patient screening in the U.S. In addition, given the availability of claims data and ICD-10 codes, these patients have an established record of engagement with healthcare services. Second, the burden of disease is high, meaning symptomatic patients are actively managed, and the associated cost of care is significant. Despite this, treatment options are limited, especially for patients with non-transfusion-dependent disease, and most patients still rely on supportive therapy.

As shown on the slide they said generated across this robust clinical program means upon potential approval, we expect to deliver a series of tourism in the treatment of the leukemia in the U S. All of which are profoundly meaningful to the lithemia patients.

Next slide please.

We're confident in our ability to deliver on the U S launch of <unk> in Telus EMEA.

The FDA approval for several reasons.

Alright, so lets him as well diagnosed due to widespread prevalence of newborn patients screening in the U S.

In addition, given the availability of claims data and ICD 10 codes. These patients have an established record of engagement with health care services.

Second the burden of disease high meaning seem too myopic patients are actively managed and the associated cost of care is significant.

Despite this treatment options are limited, especially for patients with non transfusion dependent disease and motivation do you rely on supporting therapy.

Tsveta Milanova: Third, this is a community with a high level of engagement across key thought leaders and robust patient advocacy representation. Just this month, we attended the first Thalassaemia International Federation Pan-American Conference, where we engaged in meaningful conversations with patients and physicians that reinforce our understanding of their needs. Lastly, robust preparedness supports our ability to deliver a successful launch. Our disease state education is tailored to address the diverse multicultural aspects of thalassemia. We have leveraged our connections with thought leaders to provide additional disease education for community-based physicians. Last year, we doubled our sales force to approximately 40 employees and have focused our launch planning on known treatment centers. Initial conversations with payers have been encouraging, reinforced by the compelling benefit risk profile of Pyrukynd. Please move to the next slide.

Tsveta Milanova: Third, this is a community with a high level of engagement across key thought leaders and robust patient advocacy representation. Just this month, we attended the first Thalassemia International Federation Pan-American Conference, where we engaged in meaningful conversations with patients and physicians that reinforced our understanding of their needs. Lastly, robust preparedness supports our ability to deliver a successful launch. Our disease state education is tailored to address the diverse, multicultural aspects of thalassemia, and we have leveraged our connections with thought leaders to provide additional disease education for community-based physicians. Last year, we doubled our salesforce to approximately 40 employees and have focused our launch planning on known treatment sensors. Initial conversations with payers have been encouraging, reinforced by the compelling benefit-risk profile of Pyrukynd. Please move to the next slide.

Tsveta Milanova: Third, this is a community with a high level of engagement across key thought leaders and robust patient advocacy representation. Just this month, we attended the first Thalassemia International Federation Pan-American Conference, where we engaged in meaningful conversations with patients and physicians that reinforced our understanding of their needs. Lastly, robust preparedness supports our ability to deliver a successful launch. Our disease state education is tailored to address the diverse, multicultural aspects of thalassemia, and we have leveraged our connections with thought leaders to provide additional disease education for community-based physicians. Last year, we doubled our salesforce to approximately 40 employees and have focused our launch planning on known treatment centers. Initial conversations with payers have been encouraging, reinforced by the compelling benefit-risk profile of Pyrukynd. Please move to the next slide.

Sarah This is a community with a high level of engagement across key thought leaders and robust patient advocacy representation.

Just this month, we attended the poorest the EMEA international for duration Pan American Conference, where do we engaged in meaningful conversations with patients and physicians.

Reinforce our understanding of their needs.

Luckily robust preparedness supports our ability to deliver a successful launch.

Our disease State education is say, let's do a dresden diverse multi cultural aspects of the leukemia, and we have leveraged our connections with thought leaders to provide additional disease education for community based physicians.

Last year, we doubled our sales force to approximately 40 employees and have focused our launch planning on non treatment centers.

Initial conversations with Baird had been encouraging reinforced by the compelling benefit risk profile of cytokine.

Tsveta Milanova: We have focused our capital investment on the U.S., which represents the largest commercial opportunity globally, with 6,000 diagnosed adult thalassemia patients. Our initial launch is focused on the 4,000 patients that are actively managed due to their symptomology. This patient segment includes both transfusion and non-transfusion-dependent patients who experience complications and/or are living with debilitating fatigue. Next slide, please. Our agreement with Advansanite Bioscience and Newbridge Pharmaceuticals allows us to provide sustainable, tailored access to Pyrukynd outside of the U.S. We anticipate the first potential regulatory approval in the GCC in the coming months, and I will share additional details on the commercial launch dynamics in the region shortly. In Europe, we anticipate a potential regulatory decision early next year. Here, we will work with our partner, Advansanite, on a focused country-by-country launch strategy aligned with thalassemia disease prevalence. Please move to the next slide.

Tsveta Milanova: We have focused our capital investment on the US, which represents the largest commercial opportunity globally with 6,000 diagnosed adult thalassemia patients. Our initial launch is focused on the 4,000 patients that are actively managed due to their symptomology. This patient segment includes both transfusion and non-transfusion dependent patients who experience complications and/or are living with debilitating fatigue. Next slide, please. Our agreement with Avanzanite Bioscience and NewBridge Pharmaceuticals allow us to provide sustainable tailored access to PYRUKYND outside of the US. We anticipate the first potential regulatory approval in the GCC in the coming months, and I will share additional detail on the commercial launch dynamics in the region shortly. In Europe, we anticipate a potential regulatory decision early next year. Here we will work with our partner, Avanzanite, on a focused country-by-country launch strategy aligned with the thalassemia disease prevalence. Please move to the next slide.

Please move to the next slide.

We have focused our capital investments on the U S, which represents the largest commercial opportunity globally, we see.

6000 diagnosed doubtful Asemia basin.

Our initial launch is focused on the 4000 patients.

They're actively manage their symbology.

These patient segments include bulk.

And non transfusion dependent patients, who experienced complications and for our living with debilitating fatigue.

Next slide please.

Our agreement with Ivanka, nine Bioscience, and Newbridge pharmaceuticals allow us to provide sustainable tailored access to <unk> outside of the U S.

We anticipate the first potential regulatory approval in the GCC in the coming months and now we will share additional detail on the commercial launch dynamics in the region shortly.

In Europe, we anticipate a potential regulatory decisions early next year.

We will work with our partner our bonds are nice on our focus country by country launch strategy aligns with the leukemia disease prevalent.

Tsveta Milanova: I would like to take a few minutes to double-click on the opportunity in the GCC. There are an estimated 70,000 adult and pediatric thalassemia patients in the GCC, regardless of genotype and phenotype, and the majority of this estimated prevalence is concentrated in Saudi Arabia. However, due to the lack of national registry data, we have been working with our partner, Newbridge, to refine our launch strategy. Since access in the region is fragmented, we are focused on targeting all patients actively managed at an institution, and this target launch population represents a smaller proportion of the 70,000 estimated prevalence. Importantly, we see potential to expand access by securing national procurement agreements, which can take roughly two years from approval, during which time access is granted on a patient-by-patient basis.

Tsveta Milanova: I would like to take a few minutes to double-click on the opportunity in the GCC. There are an estimated 70,000 adult and pediatric thalassemia patients in the GCC, regardless of genotype and phenotype, and the majority of this estimated prevalence is concentrated in Saudi Arabia. However, due to the lack of national registry data, we have been working with our partner, NewBridge, to refine our launch strategy. Since access in the region is fragmented, we are focused on targeting all patients actively managed at an institution, and this target launch population represents a smaller proportion of the 70,000 estimated prevalence. Importantly, we see potential to expand access by securing national procurement agreements, which can take roughly 2 years from approval, during which time access is granted on a patient-by-patient basis. Once procurement agreements are secured, we expect to further expand access agreements at an institutional level.

Please go to next slide.

I would like to take a few minutes to double click on the variety in the GCC.

There are an estimated 70000 adult and pediatric leukemia patients in the GCC, regardless of genotype and phenotype and the majority of these estimated prevalence is concentrated in Saudi Arabia.

However, due to the loss of National Registry data, we have been working with our partner in new ways to refine our long term strategy.

Do you have access in the region, it's fragmented we.

Our focus on targeting all patients actively managed.

I mean institution and this target launch population represents a smaller proportion of the 70000 estimated relevant.

Importantly, we see potential to expand access by securing national procurement agreements, which can take roughly two years from a colo.

Tsveta Milanova: Once procurement agreements are secured, we expect to further expand access agreements at an institutional level. We are thrilled to partner with Newbridge, a company with extensive experience commercializing medicines in the GCC, to potentially transform the treatment of thalassemia in Saudi Arabia and the United Arab Emirates. Please move to the next slide. With that, I will hand the call over to Tara to cover key R&D highlights from the quarter.

During which time accessing the bronchus on a patient by patient basis.

Tsveta Milanova: We're thrilled to partner with NewBridge, a company with extensive experience commercializing medicines in the GCC, to potentially transform the treatment of thalassemia in Saudi Arabia and the United Arab Emirates. Please move to the next slide. With that, I will hand the call over to Sarah to cover key R&D highlights from the quarter.

One procurement agreements are secured we expect to further expand access and getting them in at.

The institutional level.

We're thrilled to partner up with new ways, a company with extensive experience commercializing medicines in the GCC.

Potentially transform the treatment of the leukemia in Saudi Arabia, and the United Arab Emirates.

Please move to the next slide and with that I will hand, the call over to Sarah to cover our key R&D highlights from the quarter.

Sarah Gheuens: Thank you, Sarah. Next slide, please. PYRUKYND, our first-in-class PK activator, has demonstrated consistent, meaningful clinical data across multiple hemolytic anemias, reinforcing the strength of its differentiated mechanism of action as an allosteric activator of both PKR and PKM2, and the broad applicability of this unique mechanism. In pyruvate kinase deficiency, our first approved indication, treatment with PYRUKYND resulted in statistically significant improvements across multiple endpoints, highlighting improved hemoglobin levels, reduced hemolysis, and improved patient-reported outcomes. At the end of last year, we submitted a supplemental NDA for PYRUKYND for the treatment of alpha or beta thalassemia, regardless of transfusion burden. In our Phase 3 ENERGIZE and ENERGIZE-T studies, we showed statistically significant improvements on measures of anemia, including hemoglobin levels, transfusion reduction, and reduction in fatigue. We continue to partner with global health authorities on our regulatory filings and work towards our PDUFA goal date in the US.

Morgan Sanford: Thank you, Tsveta. Next slide, please. Pyrukynd, our first-in-class PK activator, has demonstrated consistent, meaningful clinical data across multiple hemolytic anemias, reinforcing the strength of its differentiated mechanism of action as an allosteric activator of both PKR and PPM2 and the broad applicability of this unique mechanism. In pyrukynd kinase deficiency, our first approved indication, treatments with Pyrukynd resulted in statistically significant improvements across multiple endpoints, highlighting improved hemoglobin levels, reduced hemolysis, and improved patient-reported outcomes. At the end of last year, we submitted a supplemental NDA for Pyrukynd for the treatment of alpha or beta thalassemia, regardless of transfusion burden. In our Phase 3 Energize and Energize-T studies, we showed statistically significant improvements on measures of anemia, including hemoglobin levels, transfusion reduction, and reduction in fatigue. We continue to partner with global health authorities on our regulatory filings and work towards our PDUFA goal date in the U.S.

Morgan Sanford: Thank you, Tsveta Milanova. Next slide, please. Pyrukynd, our first-in-class PK activator, has demonstrated consistent, meaningful clinical data across multiple hemolytic anemias, reinforcing the strength of its differentiated mechanism of action as an allosteric activator of both PKR and PPM2 and the broad applicability of this unique mechanism. In pyrukynd kinase deficiency, our first approved indication, treatment with Pyrukynd resulted in statistically significant improvements across multiple endpoints, highlighting improved hemoglobin levels, reduced hemolysis, and improved patient-reported outcomes. At the end of last year, we submitted a supplemental NDA for Pyrukynd for the treatment of alpha or beta thalassemia, regardless of transfusion burden. In our Phase 3 Energize and Energize-T studies, we showed statistically significant improvements on measures of anemia, including hemoglobin levels, transfusion reduction, and reduction in fatigue. We continue to partner with global health authorities on our regulatory filings and work towards our PDUFA goal date in the U.S.

Thank you Sarah next slide please.

<unk>, our first in class PK activator has demonstrated consistent meaningful clinical data across multiple hemolytic anemia, reinforcing the strength of its differentiated mechanism of action as an allosteric activator of both <unk> and <unk> and the broad applicability of this unique mechanism.

In pyruvate kinase deficiency, our first approved indication treatments with <unk> resulted in statistically significant improvements across multiple end points, highlighting improves hemoglobin levels, reducing hemolysis any proof of patient reported outcomes.

At the end of last year, we submitted the supplemental NDA for <unk> for the treatment of alpha or beta thalassemia, regardless of transfusion burden.

In our phase III energize and energized T studies, we showed statistically significant improvements on measures of anemia, including hemoglobin level as fusion reduction and reduction of fatigue.

Sarah Gheuens: In sickle cell disease, we have reported compelling Phase 2 data from the operationally seamless RISE UP Phase 2/3 trial in 2023 and are on track to deliver top-line results from the Phase 3 trial by the end of the year. Please move to the next slide. Last month at the European Hematology Association Congress, we had a combined 14 abstracts that led to multiple oral presentations, posters, and publications focused mostly on PYRUKYND and tebapivat. These data add to the robust body of efficacy and safety data, reinforcing the promise of PK activation and the therapeutic potential of mitapivat and tebapivat across a range of devastating rare diseases, including pyruvate kinase deficiency, thalassemia, sickle cell disease, and myelodysplastic syndromes. Please move to the next slide.

Morgan Sanford: In sickle cell disease, we have reported compelling Phase 2 data from the operationally seamless RISE UP Phase 2/3 trial in 2023 and are on track to deliver top-line results from the Phase 3 trial by the end of the year. Please move to the next slide. Last month, at the European Hematology Association Congress, we had a combined 14 abstracts that led to multiple oral presentations, posters, and publications focused mostly on Pyrukynd and tebepivat. These data add to the robust body of efficacy and safety data, reinforcing the promise of PK activation and the therapeutic potential of mitapivat and tebepivat across a range of devastating rare diseases, including pyrukynd kinase deficiency, thalassemia, sickle cell disease, and myelodysplastic syndrome. Please move to the next slide.

We continue to partner with global health authorities on our regulatory filings and work towards our <unk> goal dates in the U S.

In sickle cell disease, we have reported compelling phase II data from the operationally seamless rise up phase two three trial in 2023 and are on track to deliver top line results from the phase III trial by the end of the year. Please move to the next slide.

Last month at the European Hematology Association Congress, we had a combined 14 abstracts that led to multiple oral presentations posters and publications focused mostly on fire kind of instead of Buffy Abbas.

These data add to the robust body of efficacy and safety data reinforcing the promise of feature activation in the therapeutic potential of me stop if up and step up to give up across a range of devastating rare diseases, including five fish kinase deficiency thalassemia sickle cell disease and Myelodysplastic syndrome.

Sarah Gheuens: Our RISE-UP Phase 2 data reinforce our confidence in the potential to deliver a statistically significant improvement in hemoglobin response and reduction in analyzed rate of sickle cell pain crises, which are the dual primary endpoints for our Phase 3 trial. The occurrence and severity of sickle cell pain crises carry variability, we kept consistency across our Phase 2 and Phase 3 trials by using the same inclusion and exclusion criteria, same definition of pain crises, same adjudication committee and methodology, and by including sites from the Phase 2 in the Phase 3 trial. We hope to deliver data that can speak to the positive impact PYRUKYND can show on the totality of the disease, for example, hemolytic anemia and vaso-occlusion. Additionally, as fatigue is important to patients, we will look at the improvement in the FACIT-Fatigue scale as one of our key secondary endpoints.

Morgan Sanford: Our RISE UP Phase 2 data reinforced our confidence in the potential to deliver a statistically significant improvement in hemoglobin response and reduction in analyzed rate of sickle cell pain crises, which are the dual primary endpoints for our Phase 3 trial. As the occurrence and severity of sickle cell pain crises carry variability, we kept consistency across our Phase 2 and Phase 3 trial by using the same inclusion and exclusion criteria, same definition of pain crises, same adjudication submitted methodology, and by including sites from the Phase 2 in the Phase 3 trial. We hope to deliver data that can speak to the positive impact Pyrukynd can show on the totality of the disease, for example, hemolytic anemia and vaso-occlusion. Additionally, as fatigue is important to patients, we will look at the improvement in the Fromas Fatigue Scale as one of our key secondary endpoints.

Morgan Sanford: Our RISE UP Phase 2 data reinforced our confidence in the potential to deliver a statistically significant improvement in hemoglobin response and reduction in analyzed rate of sickle cell pain crises, which are the dual primary endpoints for our Phase 3 trial. As the occurrence and severity of sickle cell pain crises carry variability, we kept consistency across our Phase 2 and Phase 3 trials by using the same inclusion and exclusion criteria, same definition of pain crises, same adjudication submitted methodology, and by including sites from the Phase 2 in the Phase 3 trial. We hope to deliver data that can speak to the positive impact Pyrukynd can show on the totality of the disease, for example, hemolytic anemia and vaso-occlusion. Additionally, as fatigue is important to patients, we will look at the improvement in the from a fatigue scale as one of our key secondary endpoints.

Please move to the next slide.

Our rise up phase II data reinforce our confidence in the potential to deliver a statistically significant improvement in hemoglobin response, and a reduction an analyzed rate of sickle cell pain crises, which are the dual primary endpoints for our phase III trial.

As your current the severity of sickle cell pain crisis, Gary variability, we get consistency across our phase II and phase III trials by using the same inclusion and exclusion criteria same definition of pain crises famous dedications from etsy and methodology and by including sites from the phase two into phase III trials.

We hope to deliver data that can speak to the positive impact buyer pumpkin show on the pathology of the disease for example, hemolytic anemia in face of a cushion.

Morgan Sanford: We believe our robust trial design provides multiple pathways to deliver clinically meaningful data and a differentiated profile with Pyrukynd. Next slide, please. We continue to advance our pipeline and are now investigating our potential best-in-class PK activator franchise comprised of Pyrukynd and tebepivat across four rare diseases. We are also excited to progress the multiple ascending dose phase one trial for AG-181, intended for the treatment of endocannabinoids, and the single ascending dose phase one trial for AG-236, intended for the treatment of polycythemia vera. As Brian Goff mentioned, in Q2, we delivered on the two planned corporate objectives for mid-year with tebepivat and AG-236. These achievements reinforce our consistent, strong track record of delivering on our pipeline milestones. I look forward to bringing you additional updates on our pipeline as we look to develop a robust portfolio of medicines to transform the treatment of rare diseases.

Morgan Sanford: We believe our robust trial design provides multiple pathways to deliver clinically meaningful data and a differentiated profile with Pyrukynd. Next slide, please. We continue to advance our pipeline and are now investigating our potential best-in-class PK activator franchise comprised of Pyrukynd and tebepivat across four rare diseases. We are also excited to progress the multiple ascending dose phase one trial for AG-181, intended for the treatment of endocannabinoids, and the single ascending dose phase one trial for AG-236, intended for the treatment of polycythemia vera. As Brian Goff mentioned, in the second quarter, we delivered on the two planned corporate objectives for mid-year with tebepivat and AG-236. These achievements reinforce our consistent, strong track record of delivering on our pipeline milestones. I look forward to bringing you additional updates on our pipeline as we look to develop a robust portfolio of medicines to transform the treatment of rare diseases.

Sarah Gheuens: We believe our robust trial design provides multiple pathways to deliver clinically meaningful data and a differentiated profile with PYRUKYND. Next slide, please. We continue to advance our pipeline and are now investigating our potential best-in-class PK activator franchise comprised of PYRUKYND and tebapivat across 4 rare diseases. We are also excited to progress the multiple ascending dose phase 1 trial for AG-181, intended for the treatment of phenylketonuria, and the single ascending dose phase 1 trial for AG-236, intended for the treatment of polycythemia vera. As Brian mentioned, in Q2, we delivered on the two planned corporate objectives for mid-year with tebapivat and AG-236. These achievements reinforce our consistent, strong track record of delivering on our pipeline milestones. I look forward to bringing you additional updates on our pipeline as we look to develop a robust portfolio of medicines to transform the treatment of rare diseases.

Additionally, at fatigue is important to patients we will look at the improvements in the from its fifth big scale as one of our key secondary endpoints.

We believe our robust trial design provides multiple pathways to deliver clinically meaningful data and a differentiated profile with prior guidance.

Next slide please.

We continue to advance our pipeline and are now investigating our potential best in class PK activator franchise comprised of archives and step up give up across for rare diseases.

We are also excited to progress the multiple ascending dose phase one trial for <unk>, one intended for the treatment of phenylketonuria in the single ascending dose phase one trial for <unk> three six incentives for the treatment of Polycythemia Vera.

As Brian mentioned in the second quarter, we delivered on the two planned corporate objective for midyear with the pick up in <unk>.

These achievements reinforce our consistent strong track records of delivering on our pipeline milestones.

I look forward to bringing you additional updates on our pipeline as we look to develop a robust portfolio of medicines to transform the treatment of rare diseases with that please move to the next slide and I will hand, the call back to Brian for closing remarks.

Morgan Sanford: With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

Sarah Gheuens: With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

Tsveta Milanova: Thank you, Sarah. Next slide, please. In Q2, we made strong progress against our 2025 priorities

Brian Goff: Thank you, Sarah. Next slide, please. In Q2, we made strong progress against our 2025 priorities

Brian Goff: Thank you, Sarah. Next slide, please. In the second quarter, we made strong progress against our 2025 priorities. We achieved important milestones to advance tebapivat and AG-236, two assets with potential to expand our reach into new rare disease indications. We believe 2025 will be a breakout year for Agios Pharmaceuticals as we make strides towards the potential launch of Pyrukynd in thalassemia in the U.S., Phase 3 RISE UP readout in sickle cell disease, and continued advancement of our mid and early stage pipeline. Please move to the next slide. In closing, Agios Pharmaceuticals has the necessary ingredients to deliver innovative medicines to rare disease patients in need, driving sustainable growth and unlocking long-term shareholder value.

Brian Goff: We achieved important milestones to advance tebapivat and AG-236, two assets with potential to expand our reach into new rare disease indications. We believe 2025 will be a breakout year for Agios as we make strides towards the potential launch of PYRUKYND and thalassemia in the US, Phase 3 RISE UP readout in sickle cell disease, and continued advancement of our mid and early-stage pipeline. Please move to the next slide. In closing, Agios has the necessary ingredients to deliver innovative medicines to rare disease patients in need, driving sustainable growth and unlocking long-term shareholder value. At our core, we are fueled by our connections with the rare disease communities we serve, enabling us to deliver clinical benefits that matter to patients with a tailored commercial model to best meet patients where they are. Importantly, we're on our way to building a diversified rare disease portfolio.

Thank you Sir our next slide please in the second quarter, we made strong progress against our 2025 priorities.

We achieved important milestones to advance type a pipette and <unk> 200, 362 assets with potential to expand our reach into new rare disease indications.

We believe 2025 will be a breakout year for <unk> as we make strides towards the potential launch of <unk> imbalance EMEA and the U S. B.

Phase III rise up readout in sickle cell disease, and continued advancement of our mid and early stage pipeline. Please move to the next slide.

In closing our Geos has the necessary ingredients to deliver innovative medicines to rare disease patients in need driving sustainable growth and unlocking long term shareholder value.

Brian Goff: At our core, we are fueled by our connections with the rare disease communities we serve, enabling us to deliver clinical benefits that matter to patients with a tailored commercial model to best meet patients where they are. Importantly, we're on our way to building a diversified rare disease portfolio. We are rapidly advancing a best-in-class PK activator franchise with potential across four indications, and we look forward to providing future updates on our early stage pipeline with the opportunity to accelerate our growth outside of hematology. Before we move to Q&A, I'd like to extend my appreciation to the investigators and patients whose participation, partnership, and trust have been invaluable to our development work, and of course, the Agios Pharmaceuticals team who continue to inspire me every day. We look forward to what's ahead as we strive to redefine the future of rare diseases.

At our core we are fueled by our connections with the rare disease communities, we serve enabling us to deliver clinical benefits that matter to patients with the tailored commercial model to best meet patients where they are.

Brian Goff: We are rapidly advancing a best-in-class PK activator franchise with potential across four indications, and we look forward to providing future updates on our early-stage pipeline with the opportunity to accelerate our growth outside of hematology. Before we move to Q&A, I'd like to extend my appreciation to the investigators and patients whose participation, partnership, and trust have been invaluable to our development work. Of course, the Agios team, who continue to inspire me every day. We look forward to what's ahead as we strive to redefine the future of rare diseases. With that, I'd like to open the call for questions. Operator, please open the line.

Importantly, we're on our way to building a diversified rare disease portfolio.

We are rapidly advancing a best in class PK activator franchise with potential across four indications and we look forward to providing future updates on our early stage pipeline with the opportunity to accelerate our growth outside of hematology.

Before we move to Q&A I'd like to extend my appreciation to the investigators and patients whose participation partnership and trust had been invaluable to our development work and of course, the <unk> team who continue to inspire me every day.

Brian Goff: With that, I'd like to open the call for questions. Operator, please open the line.

We look forward to what's ahead as we strive to redefine the future of rare diseases with that I'd like to open the call for questions. Operator, Please open the line.

Operator: Thank you. To ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. We ask that you please limit yourself to two questions. One moment while we compile our Q&A roster. Our first question is gonna come from the line of Eric Schmidt with Cantor. Your line is open. Please go ahead.

Operator: Thank you. To ask a question, please press *11 on your telephone and wait for your name to be announced. To withdraw your question, please press *11 again. We ask that you please limit yourself to two questions. One moment while we compile our Q&A roster. Our first question is going to come from the line of Eric Schmidt with Cantor Fitzgerald. Your line is open. Please go ahead.

Operator: Thank you. To ask a question, please press star one-one on your telephone and wait for your name to be announced. To withdraw your question, please press star one-one again. We ask that you please limit yourself to two questions. One moment while we compile our Q&A roster. Our first question is going to come from the line of Eric Schmidt with Cantor. Your line is open. Please go ahead.

Thank you to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, we ask that you. Please limit yourself to two questions one moment, while we compile our Q&A roster.

[Analyst] (Cantor Fitzgerald): Hi. Good morning, everyone. This is Imogen on for Eric. I think in the past, you've said that you would update investors on any change to mitapivat safety profile, including any cases of liver toxicity outside of thalassemia. Is there anything new that you have to report there?

Imogen Mansfield: Hi. Good morning, everyone. This is Imogen on for Eric. I think in the past, you've said that you would update investors on any change to mitapivat safety profile, including any cases of liver toxicity outside of thalassemia. Is there anything new that you have to report there?

Emma Joon: Hi. Good morning, everyone. This is Emma Joon on for Eric. I think in the past, you said that you would update investors on any change to a mitapivat safety profile, including in cases of liver toxicity outside of thalassemia. Is there anything new that you have to report there?

Emma Joon: Hi, good morning, everyone. This is Emma Joon on for Eric. I think in the past, you said that you would update investors on any change to a mitapivat safety profile, including in cases of liver toxicity outside of thalassemia. Is there anything new that you have to report there?

And our first question is going to come from the line of Eric Schmidt with Cantor. Your line is open. Please go ahead.

Hi, Good morning, everyone. This is imaging on for Eric.

I think in the policy that you would update investors on any change to make it to that safety profile in creating one of the cases of liver toxicity outside of policy.

Brian Goff: Morning, Imogen. It's Brian. Thanks a lot for the question. I'll have Sarah comment on that first one with respect to any updates in the safety profile.

Is that anything that you have to report that.

Good morning, it's Brian Thanks, a lot for the question I'll have Sarah comment on that first one with respect to any updates in the safety profile.

Sarah Gheuens: Good morning. No, no updates to the safety profile. That, that's it, really.

Sarah Gheuens: Good morning. There are no updates to the safety profile. That is it, really.

Sarah Gheuens: Good morning. No, no updates to the safety profile. That, that's it, really.

So good morning, so no no updates to the safety profile of that.

[Analyst] (Cantor Fitzgerald): Okay, great. Thank you. Then one quick follow-up. On the GCC approval dates, is there any more color you could share on that? Are you expecting it maybe just after the US approval?

Imogen Mansfield: Okay, great. Thank you. Then one quick follow-up. On the GCC approval dates, is there any more color you could share on that? Are you expecting it maybe just after the US approval?

Emma Joon: Okay. Great. Thank you. Then one quick follow-up. On the AG-236 approval dates, is there any more Cecilia Jones could share on that? Are you expecting it maybe just after the U.S. approval?

Emma Joon: Okay, great. Thank you. One quick follow-up. On the GCC approval dates, is there any more color you could share on that? Are you expecting it maybe just after the U.S. approval?

That's it really.

Okay, great. Thank you and then one quick follow up on the GCC approval dates is there any more color you could share on that I'm expecting it maybe just after the U S approval.

Brian Goff: Well, I will say, just reflecting on what we had announced in December of last year, I'm really proud of the fact that the team has submitted, this was a first for Agios, simultaneously across 4 different regions. All we can share at this point is that we're actively in discussions across all 4 regions, and we look forward to having the opportunity to give updates on the status of those reviews. I will also say that Sveta and her team are certainly ready from a commercialization standpoint.

Brian Goff: I will say, just reflecting on what we had announced in December of last year, I am really proud of the fact that the team has submitted—this was a first for Agios Pharmaceuticals—submitted simultaneously across four different regions. All we can share at this point is that we are actively in discussions across all four regions, and we look forward to having the opportunity to give updates on the status of those reviews. I will also say that Tsveta Milanova and her team are certainly ready from a commercialization standpoint.

Well I will say just reflecting on what we had announced in December of last year I'm really proud of the fact that the team has submitted this was the first raggio submitted simultaneously across four different regions.

All we can share at this point is that we are.

We're actively in discussions across all four regions and we look forward to having the opportunity to give updates on the status of those reviews and I will also say that Sarah and her team are certainly ready from a commercialization standpoint.

[Analyst] (Cantor Fitzgerald): Okay, great. Thanks very much.

Imogen Mansfield: Okay, great. Thanks very much.

Emma Joon: Okay. Great. Thanks very much.

Emma Joon: Okay, great. Thanks very much.

Brian Goff: You're welcome.

Operator: Thank you. One moment as we move on to our next question. Our next question is gonna come from the line of Marc Frahm with TD Cowen. Your line is open. Please go ahead.

Operator: Thank you. One moment as we move on to our next question. Our next question is going to come from the line of Marc Frahm with TD Cowen. Your line is open. Please go ahead.

Okay, great. Thanks, very much Youre welcome.

And one moment as we move on to our next question.

Marc Frahm: Thanks for taking my questions. Maybe just with the thal review ongoing, are you able to comment on, you know, if you're maybe in labeling discussions yet? Obviously, safety information is going to need to be at least somewhat updated just to account for the fact that thalassemia is now, well, hopefully going to become an approved indication. What's the latest thoughts on kind of how you're anticipating that part of the label to read? I will probably have a follow-up question.

Marc Frahm: Thanks for taking my questions. Maybe just with the thal review ongoing, are you able to comment on, you know, if you're maybe in labeling discussions yet? Obviously safety information is gonna need to be at least somewhat updated just to account for the fact that thalassemia is now, well, hopefully going to become an approved indication. What's the latest thoughts on kind of how you're anticipating that part of the label to read? Then I'll probably have a follow-up question.

Our next question is going to come from the line of Marc Frahm with TD Cowen. Your line is open. Please go ahead.

Hi, Thanks for taking my questions.

Just with the salary review ongoing.

Comment on if you may begin labeling discussions yet.

And obviously safety information is going to need to be to be somewhat updated just to account for the fact that <unk> is now.

Hopefully, it's going to become an approved indication.

Brian Goff: Thanks, Marc. Sarah can start.

Brian Goff: Yeah. Thanks, Marc. Sarah can start.

What's the latest thoughts on kind of how youre anticipating that part of the label to read.

Sarah Gheuens: Sure. Thanks, Marc. Well, maybe just a recap, but as you know, we've submitted to, as Brian just mentioned, 4 different regions for the indication of thalassemia based on our 2 well-controlled trials that met the primary and key secondary endpoints in both. That's the benefit part. You mentioned on the risk side, we have of course the hepatocellular injury, which you can already see reflected in the PKD label that was based on the thalassemia observation. We do at minimum anticipate there the updates in the PKD label to reflect the indication statement and the dose to be changed to, you know, to thalassemia and 100 mg BID.

Sarah Gheuens: Sure. Thanks, Marc. So, maybe just to recap, as you know, we've submitted, as Brian Goff just mentioned, four different regions for the indication of thalassemia based on our two well-controlled trials that met the primary and key secondary endpoints in both. That's the benefit part. You mentioned on the risk side, we have, of course, the hepatocellular injury, which you can already see reflected in the Pyrukynd label that was based on the thalassemia observations. So we do, as minimum, anticipate there the updates in the Pyrukynd label to reflect the indication statements and the dose to be changed to the two thalassemia and 100 milligrams bid. The process and the review are, of course, ongoing, and the FDA only provides you an end date of the complete review. The final label, that's what we will know at the PDUFA date.

Sarah Gheuens: Sure. Thanks, Marc. So, maybe just to recap, as you know, we have submitted to, as Brian Goff just mentioned, four different regions for the indication of thalassemia based on our two well-controlled trials that met the primary and key secondary endpoints in both. So, that is the benefit part. You mentioned on the risk side, we have, of course, the hepatocellular injury, which you can already see reflected in the Pyrukynd label that was based on the thalassemia observations. So, we do, as minimum, anticipate there the updates in the Pyrukynd label to reflect the indication statements and the dose to be changed to the two thalassemia and 100 milligrams bid. But the process and the review are, of course, ongoing, and the FDA only provides you an end date of the complete review. So, the final label, that is what we will know at the PDUFA date.

Then I'll probably have a follow up question yes.

Thanks, Mark So Sarah can start sure. Thanks Marc.

So maybe just a recap.

No.

Submit it to as Brian just mentioned for different regions.

For the indication of thalassemia based on our two well controlled trials met the primary and key secondary endpoints in both.

The benefits Bart you mentioned on the risk side.

Of course, the hip the cellular injury, which you can already see reflected in the PK D. A label that was based on the thalassemia observation and so we do at minimum anticipate there'd be updates in the <unk> label to reflect the indication statement and the dose to be change too.

Sarah Gheuens: The process and the review are of course ongoing and the FDA only, you know, provides you an end date of the complete review. The final label, that's what we will know at the PDUFA date.

No.

$2 senior in a 100 milligrams B I D.

But the process and the review our of course ongoing in the FDA only provide.

Provide you an end date of the complete review so the final label, that's what people know us for two five days.

Marc Frahm: Okay, that's helpful. This is more for Sveta and Cecilia. Just the SG&A spend has, you know, been ticking up, obviously as you build out and prepare for that thalassemia launch. Should we view this as fully built out now and this is kind of run rate or are there still kind of meaningful step-ups that we should be expecting going forward as the launch actually starts?

Marc Frahm: Okay. That is helpful. This is Marc for Tsveta Milanova and Cecilia Jones. The SG&A spend has been ticking up, obviously, as you build out and prepare for that thalassemia launch. Should we view this as fully built out now and this is kind of the run rate, or are there still kind of meaningful step-ups that we should be expecting going forward as the launch actually starts?

Marc Frahm: Okay, that is helpful. This is Marc for Tsveta Milanova and Cecilia Jones. The SG&A spend has been ticking up, obviously, as you build out and prepare for that thalassemia launch. Should we view this as fully built out now and this is kind of the run rate, or are there still kind of meaningful step-ups that we should be expecting going forward as the launch actually starts?

Okay. That's helpful and then.

Maybe this is more for Fedex Julia just the.

SG&A spend has been picking up obviously as you build out.

Prepare for that thalassemia launch.

Should we view this is fully built out now and this is kind of the run rate or are there still a meaningful step up that we should be expecting going forward as.

Brian Goff: Yeah. Maybe Cecilia Jones can start on the financial aspects, and then Tsveta Milanova always loves the opportunity to be able to talk about how well-prepared her team is for potential launches ahead.

Brian Goff: Cecilia can start on the financial aspects, and then Tsveta Milanova always loves the opportunity to be able to talk about how well-prepared her team is for potential launches ahead.

Brian Goff: Yeah. Maybe, Cecilia can start on the financial aspects. Sveta always loves the opportunity to be able to talk about how well prepared her team is for potential launches ahead.

That's the launch actually starts.

Yes, maybe.

So you can start on the financial aspects and then instead of always loves the opportunity to be able to talk about how well prepared for team is for potential launches ahead.

Cecilia Jones: Thanks, Marc. Yeah, from a financials perspective, we do expect to see a little bit more growth on the SG&A side for thalassemia. You're right, we based the

Cecilia Jones: Thanks, Marc. Yeah, from a financials perspective, we do expect to see a little bit more growth on the SG&A side for thalassemia. You're right, we based the The bulk of the infrastructure, the sales teams and customer-facing teams, starting last year after the trials are read out. We do have some launch-related expenses that would obviously only happen, you know, upon approval. We do see some more coming, potentially after that.

Tsveta Milanova: Thanks, Marc. From a financial perspective, we do expect to see a little bit more growth on the SG&A side for thalassemia. You are right. We built the bulk of the infrastructure with the sales teams and customer-facing teams starting last year after the trials read out. But we do have some launch-related expenses that would obviously only happen upon approval. So we do see some more coming, potentially, after that.

Sarah Gheuens: Thanks, Marc. From a financial perspective, we do expect to see a little bit more growth on the SG&A side for thalassemia. You are right. We built the bulk of the infrastructure with the sales teams and customer-facing teams starting last year after the trials read out. We do have some launch-related expenses that would obviously only happen upon approval. So, we do see some more coming potentially after that. Absolutely. The team, I can tell you the team is ready for a potential launch in thalassemia. As Cecilia Jones mentioned, we have deployed the field trust-facing organization late last year, and that includes the 40, about 40 people in the sales organization, but also a cross-functional team that is dealing with a lot of different customers. We are excited about having the potential to provide Pyrukynd in thalassemia, of course, pending FDA approval in the U.S.

[Company Representative] (Agios Pharmaceuticals): The bulk of the infrastructure, the sales teams and customer-facing teams, starting last year after the trials are read out. We do have some launch-related expenses that would obviously only happen, you know, upon approval. We do see some more coming, potentially after that.

Thanks, Mike Yeah from a financial perspective, we do expect to see a little bit more growth on the SG&A side propel asemia you're right we've been.

The bulk of the infrastructure or the sales teams all customer facing team starting last year. After the trials read out, but we do have some launch related expenses that would obviously only happened upon approval. So we do see some work coming.

Tsveta Milanova: Yeah, absolutely. I can tell you the team is ready for a potential launch in thalassemia. As Cecilia mentioned, we've deployed the field sales-facing organization late last year. That includes the 40, about 40 people in the sales organization, but also a cross-functional team that is to interact with different customers. We are excited about having the potential to provide PYRUKYND in thalassemia, of course, pending FDA approval in the US. We're looking forward to give updates when possible.

Sarah Gheuens: Absolutely. The team, I can tell you the team is ready for a potential launch in thalassemia. As Cecilia Jones mentioned, we have deployed the field trust-facing organization late last year, and that includes the 40, about 40 people in the sales organization, but also a cross-functional team that is dealing with a lot of different customers. We are excited about having the potential to provide Pyrukynd in thalassemia, of course, pending FDA approval in the U.S. We are looking forward to give updates when possible.

Essentially after that.

Yes, absolutely.

The team I can tell the team is ready for a potential launch into Lithemia Cecilia mentioned.

Deployed the field facing organization late last year.

And that includes the 40 about 40 people in the sales organization, but also our cross functional team that is.

Lots of different customers.

We are excited about having the potential to provide a vital comes into leukemia or spending is pretty low in the U S.

Sarah Gheuens: We are looking forward to give updates when possible.

[Analyst] (Bank of America): Great. Thank you.

Marc Frahm: Great. Thank you.

We're looking forward to them, we'll give updates when possible.

Brian Goff: Susan.

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

Brian Goff: You bet.

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

Brian Goff: You bet.

Operator: Thank you. One moment for our next question. Our next question comes from the line of Sylvain Richter with Goldman Sachs. Your line is open. Please go ahead.

Great. Thank you.

You bet.

Thank you one moment for our next question.

Salveen Richter: Good morning. Thanks for taking my question. As you look to the upcoming PDUFA here for zal, and focus on the launch, could you just help us understand the initial target patient population that you'll be addressing or just be targeting here initially?

Salveen Richter: Good morning. Thanks for taking my question. As you look to the upcoming PDUFA here for Pyrukynd and focus on the launch, could you just help us understand the initial target patient population that you will be addressing or just be targeting here initially?

Sylvain Richter: Good morning. Thanks for taking my question. As you look to the upcoming PDUFA here for Pyrukynd and focus on the launch, could you just help us understand the initial target patient population that you will be addressing or just be targeting here initially?

Our next question comes from the line of Celgene Ritchie with Goldman Sachs. Your line is open. Please go ahead.

Good morning, Thanks for taking my question as you look to the upcoming produced by here for <unk> and.

Focus on the launch could you just help us understand the initial target patient population that youll be addressing.

Brian Goff: Yeah. Thanks a lot, Salveen. And again, I'll turn that one over to Tsveta.

Brian Goff: Yeah, thanks a lot, Sylvain. I'll turn that one over to Tsveta.

Brian Goff: Yeah. Thanks a lot, Salveen. Again, I'll turn that one over to Sveta.

Tsveta Milanova: Absolutely. From a commercial perspective, thalassemia is really an attractive indication for us to potentially launch next. The reason for that is that the patients with thalassemia are actually diagnosed and well known to the healthcare system in the US. There is a great data based on the ICD-10 codes in the US, which we have been able to validate through our interactions with healthcare professionals. That gave us a lot of clarity, not only where patients are currently being managed, but also what the patients potentially we should prioritize and focus at launch. When you think about which patients are really the most appropriate for our initial launch target, these are about 4,000 patients out of the 6,000 diagnosed adult patients in the US.

Sarah Gheuens: Absolutely. From a commercial perspective, thalassemia is really an attractive indication for us to potentially launch next. The reason for that is that the patients with thalassemia are actually diagnosed and well known to the healthcare system in the U.S. There is great data based on the ICD-10 code in the U.S., which we have been able to validate through our interactions with healthcare professionals. That gave us a lot of clarity, not only where patients are currently being managed, but also what patients potentially we should prioritize and focus at launch. When you think about which patients are really the most appropriate for our initial launch target, these are about 4,000 patients out of the 6,000 diagnosed adult patients in the U.S.

I would just be targeting here initially.

Yes, Thanks a lot.

Again, I'll turn that one over to settle.

Absolutely.

So the from a commercial core express paperless senior Israeli.

An attractive indication for us to potentially launch next and the reason for that is is that the patients with the leukemia are actually diagnosed and.

And well known for the health care system in the U S. But there is a great data based on the ICD 10 codes in the U S, which we have been able to validate through our interactions with health care professionals and that gave us a lot of clarity not only.

Their patients are currently being managed but also what the patients are substantially we should prioritize and focus at launch when you think about which patients are really the most appropriate for our initial launch target. These are about 4000 patients out of the 6000 diagnosed adult patients in the U S and the way with Praluent.

Tsveta Milanova: The way we prioritize these patients is based on their symptomology, the fact that they're engaged with the healthcare system, and they potentially will require additional management and treatment. In this group of patients, you see both transfusion-dependent patients who might be looking to reduce their transfusion burden, as well as non-transfusion dependent patients who are symptomatic, and they're experiencing fatigue and other complications of the disease, and both the patient and the physician might be looking for additional management and treatment. As I said, the team is very well prepared for the launch, and we have the opportunity to actually engage with these accounts in advance of the launch. Very importantly for us, it's important that to remember and recognize that thalassemia is a disease with high unmet need.

Sarah Gheuens: The way we've prioritized these patients is based on their symptomology, the fact that they're engaged with the healthcare system, and they potentially will require additional management and treatment. In this group of patients, you see both transfusion-dependent patients who might be looking to reduce their transfusion burden, as well as non-transfusion-dependent patients who are symptomatic, they're experiencing fatigue and other complications of the disease, and both the patient and the physician might be looking for additional management and treatment. As I said, the team is very well prepared for the launch, and we have the opportunity to actually engage with this account in advance of the launch. Very importantly for us, it's important to remember and recognize that thalassemia is a disease with high unmet needs. About two-thirds of the patients have no available treatment in the U.S.

These patients is based on their Siem technology. The fact that they are engaged with the health care system and they potentially will require additional management and treatments and indeed, but it'll be inflation equation you'd see both transfusion dependent patients.

I'll be looking to reduce their transfusion burden as well as non transfusion dependent patients where it seemed to take they are experiencing but the H and other complications of the disease and both the patient and the physician might be looking for additional management and treatment.

As I said the team is very well prepared for the launch.

And we have therefore Julien.

<unk> actually engaged with these accounts in advance of the launch very importantly for us it's in.

Tsveta Milanova: About two-thirds of the patients have no available treatment in the US. That unmet need was really reinforced through our interactions with both patients and physicians earlier in the month, where we had the opportunity to actually attend the Thalassaemia International Federation Pan American Conference, which gave us a lot of energy and excitement about the potential launch in the future.

Four times debt.

Remember it and recognize that the leukemia is a disease with high unmet needs about two thirds of the patients have no available treatment in the U S.

Sarah Gheuens: That unmet need was really reinforced through our interactions with both patients and physicians earlier in the month, where we had the opportunity to actually attend the Senior Interventional Physician Pan-American Conference, which gave us a lot of energy and excitement about the potential launch in the future.

Sarah Gheuens: That unmet need was really reinforced through our interactions with both patients and physicians earlier in the month, where we had the opportunity to actually attend the 13th annual Pan-American Conference, which gave us a lot of energy and excitement about the potential launch in the future.

And therefore need was really reinforced through our interactions with both patients and physicians.

Earlier in the month, where we had the opportunity to actually bend. The see me Internet function by an American conference, which gave US a lot of energy and excitement about the potential launch in the future.

Brian Goff: That's great. Salveen, just to go back to the numbers for a second, Tsveta Milanova made the point that a lot of times we get asked about how solid are those numbers, the 4,000 patients. It is a pretty important point that these ICD-10 codes have been in place for quite a long time in thalassemia. So there's a lot of rigor around those numbers. I will just point out that's in contrast to PKD, where literally the codes were established right before launch. So it's a very different dynamic. Maybe I will just ask Cecilia Jones to comment on the look ahead from a revenue perspective with a potential launch, what the fourth quarter could look like.

Brian Goff: Yeah, that's great. Sylvain, just to go back to the numbers for a second, Tsveta Milanova made the point that a lot of times we get asked about how solid are those numbers, the 4,000 patients. It is a pretty important point that these ICD-10 codes have been in place for quite a long time in thalassemia. So, there's a lot of rigor around those numbers. I'll just point out that's in contrast to PKD, where literally the codes were established right before launch. So, it's a very different dynamic. Maybe I'll just ask Cecilia Jones to comment on the look ahead from a revenue perspective with a potential launch, what the fourth quarter could look like.

Brian Goff: Yeah, that's great. Salveen, just to go back to the numbers for a second. Tsveta made the point that a lot of times we get asked about how, you know, how solid are those numbers, the 4,000 patients. It is a pretty important point that these ICD-10 codes have been in place for quite a long time in thalassemia. There's a lot of rigor around those numbers. I'll just point out that's in contrast to PKD, where literally the codes were established right before launch. It's a very different dynamic. Maybe I'll just ask Cecilia to comment on the look ahead for from a revenue perspective with a potential launch, what Q4 could look like.

Great and solving just to go back to the numbers for a second set of made the point that a lot of times, we get asked about how solid our those numbers to 4000.

Patients. It is a pretty important point that these ICD 10 codes have been in place for quite a long time in thalassemia. So theres a lot of rigor around those numbers and I'll just point out that's in contrast to TKD, where literally the codes were established right before launch so it's a very different dynamic.

[Company Representative] (Agios Pharmaceuticals): Yeah. Thanks, Brian. Given the expected goal of PDUFA in September and the time it takes between a prescription and patients initiating treatment from a revenue perspective for this year, 2025, we don't expect thalassemia revenues to be material.

Cecilia Jones: Yeah. Thanks, Brian. Given the expected goal of PDUFA in September and the time it takes between a prescription and patients initiating treatment from a revenue perspective for this year, 2025, we don't expect thalassemia revenues to be material.

Tsveta Milanova: Yes. Thanks, Brian. Given the expected goal of PDUFA in September and the time it takes between a PDUFA and patients initiating treatment from a revenue perspective, for 2025, we don't expect thalassemia revenues to be material.

Sarah Gheuens: Yes, thanks, Brian. Given the expected goal of PDUFA in September and the time it takes between a PF and patients initiating treatment from a revenue perspective for this year, 2025, we don't expect thalassemia revenues to be material.

And maybe I'll just ask phacelia to comment on the look ahead for from a revenue perspective with a potential launch what fourth quarter could look like yeah. Thanks, Bryan So given the expected coal producer in September at the time it takes between a PDF and patients initiating treatment from a revenue perspective for this year 2025, we don't expect that I've seen.

Brian Goff: Yeah. Thanks.

Brian Goff: Yep. Thanks.

Brian Goff: Yes, thanks.

Operator: Thank you. One moment as we move on to our next question. Our next question comes from the line of Emily Bodnar with H.C. Wainwright. Your line is open. Please go ahead.

Operator: Thank you. One moment as we move on to our next question. Our next question comes from the line of Emily Bodner with HC Wainwright. Your line is open. Please go ahead.

Revenues to be material.

Thanks.

Thank you and one moment as we move on to our next question.

Emily Bodnar: Hi. Good morning. Thanks for taking the questions. I guess for the first one, maybe if you could talk about the pediatric opportunity for thalassemia and if you have any timing for potential FDA filing there. Just maybe if you could confirm that you haven't had any changes to either access or, I guess, tone of speaking to the FDA in kind of recent weeks, given some of the news going on there. Thanks.

Emily Bodner: Hi. Good morning. Thanks for taking the questions. For the first one, maybe if you could talk about the pediatric opportunity for thalassemia and if you have any timing for potential FDA filing there. Then just maybe if you could confirm that you haven't had any changes to either access or, I guess, tone of speaking to the FDA in recent weeks, given some of the news going on there. Thanks.

Emily Bodner: Hi, good morning. Thanks for taking the questions. For the first one, maybe if you could talk about the pediatric opportunity for thalassemia and if you have any timing for potential FDA filing there. Then just maybe if you could confirm that you haven't had any changes to either access or, I guess, tone of speaking to the FDA in recent weeks, given some of the news going on there. Thanks.

Our next question comes from the line of Ed <unk>.

With H C. Wainwright. Your line is open. Please go ahead.

Hi, good morning, Thanks for taking the questions I guess the first one maybe if you could talk about the pediatric opportunity for thalassemia and if you have any timing for potential FDA filing there and then just maybe if you could confirm that you haven't thought it made changes to either access or I guess tone.

Brian Goff: Sure. Thanks, Emily. How about Sveta can start on pediatric from a commercial perspective, and then Sarah can reflect on the trials and the pathway ahead.

Brian Goff: Sure. Thanks, Emily. Tsveta Milanova can start on pediatric from a commercial perspective, and then Sarah Gheuens can reflect on the trials and the pathway ahead.

Brian Goff: Sure. Thanks, Emily. How about Tsveta Milanova can start on pediatric from a commercial perspective, and then Sarah Gheuens can reflect on the trials and the pathway ahead.

Speaking to the FDA in kind of recent weeks given.

And it was going on there thanks.

Sure. Thanks Emily.

Federal can start on pediatric from a commercial perspective, and then Sarah can reflect on.

Tsveta Milanova: Absolutely. There are about 8,000 thalassemia patients in the US. As we've said, about 6,000 of those are adults, so the remaining 2,000 are pediatric patients. Of course, it is a genetic disease where the patients are diagnosed at birth. There is an availability of newborn screening, so there is a high diagnosis rate in that disease. There is always a high unmet need and an opportunity for us to provide value in pediatric patients. With that, I'll hand it over to Sarah.

Sarah Gheuens: Absolutely. So, there are about 8,000 thalassemia patients in the U.S. As we said, about 6,000 of those are adults, so the remaining 2,000 are pediatric patients. Of course, it is a genetic disease where the patients are diagnosed at birth. There is an availability of newborn screening, so there is a high diagnosis rate in that disease, and there is always a high unmet need and an opportunity for us to provide value in pediatric patients. With that, I will hand it over to Sarah. The way we are approaching pediatric development is we wait for the benefit-risk profile in adults, which we now have. The plan for thalassemia indication is doing exactly the same what we have done for the Pyrukynd kinase deficiency indication with an expansion by running the trials in the pediatric patient population.

Sarah Gheuens: Absolutely. There are about 8,000 thalassemia patients in the U.S. As we said, about 6,000 of those are adults. The remaining 2,000 are pediatric patients. Of course, it is a genetic disease where the patients are diagnosed at birth. There is an availability of newborn screening, so there is a high diagnosis rate in that disease, and there is always a high unmet need and an opportunity for us to provide value in pediatric patients. With that, I will hand it over to Sarah. The way we are approaching pediatric development is we wait for the benefit-risk profile in adults, which we now have. The plan for thalassemia indication is doing exactly the same what we have done for the Pyrukynd kinase deficiency indication with an expansion by running the trials in the pediatric patient population. Then once that data is available, indeed, deliver that to regulators for review.

The trials and the pathway ahead.

Absolutely. So there are about 8000 silver senior patients in the U S. As we said about six thousands of builds are down so the remaining 2000 carpathia application.

Of course, it is a genetic disease, where the patients are diagnosed at birth.

Availability of a newborn screening. So there were there was a high diagnosis rate in that disease.

Sarah Gheuens: The way we are approaching pediatric development is we wait for the benefit risk profile in adults, which we now have. The plan for thalassemia indication is doing exactly the same what we have done for the pyruvate kinase deficiency indication with an expansion by running the trials in the pediatric patient population. Once that data is available, indeed, deliver that to regulators for review.

There is always a high unmet need and an opportunity for us to provide value in pediatric patients.

I'll turn it over to Sarah.

<unk>.

The way, we are approaching pediatric development be waste for the benefit risk profile in adults, which we now have until the plan for thalassemia indications doing exactly the same what we have done for the pyruvate kinase deficiency indication with an expansion by running the trials in the pediatric patient population and then.

Sarah Gheuens: Then once that data is available, indeed, deliver that to regulators for review.

Brian Goff: Emily, if I heard the second part of your question, it was about FDA interactions. Of course, we are not going to talk about specifics, but anything you want to add, Sarah, about our engagement?

Brian Goff: If I heard the second part of your question, it was about FDA interactions. Of course, we are not going to talk about specifics, but anything you want to add, Sarah, about our engagement?

Brian Goff: I think, Emily, if I heard the second part of your question about was about FDA interactions. Of course, we're not gonna talk about specifics, anything you wanna add, Sarah, about our engagement?

Once that data is available indeed.

Delivery, that's to regulators for review and.

I think Emily if I heard the second part of your question.

Sarah Gheuens: No, we always pride ourselves on collaborative engagements and relationships with all of the regulators that we interact with. I know the disruption in the news and we have not experienced like, major disruptions in our, in our team engagements with the FDA. It remains like a collaborative engagement.

Sarah Gheuens: No. We always pride ourselves on collaborative engagements and relationships with all of the regulators that we interact with. So, I know the disruption in the news, and we have not experienced major disruptions in our team engagements with the FDA. It remains like a collaborative engagement.

Sarah Gheuens: No, we always pride ourselves on collaborative engagements and relationships with all of the regulators that we interact with. So, I know the disruption in the news, and we have not experienced major disruptions in our team engagements with the FDA. It remains like a collaborative engagement.

FTA interactions of course, we're not going to talk about specifics, but anything you want to add Sarah about.

Our engagement no we always pride ourselves on collaborative engagements and.

Relationships with all of our all of the regulators that we interact with so I know the disruption in the news.

We have not experienced like major disruptions in our in our team engagements with the FDA and until it's remains like a collaborative engagements.

Tsveta Milanova: All right. Thank you.

Emily Bodnar: All right. Thank you.

Emily Bodner: All right. Thank you.

Brian Goff: You're welcome.

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

Yeah.

Alright, thank you.

You're welcome thank you.

Next question.

[Analyst] (Bank of America): Hey, guys, this is Matthew on for Alec. Thanks for taking our question. Maybe first from us. I know the initial focus of the launch is on higher frequency of visit patients. Curious for those outside the initial focus, what the key points of education are to drive uptake and whether that differs US versus ex-US. Maybe second question on the early-stage pipeline. Curious if there has been any change to your development plans in PKU after the approval of PTC's second.

Matthew Guggenbiller: Hey, guys, this is Matthew on for Alec. Thanks for taking our question. Maybe first from us. I know the initial focus of the launch is on higher frequency of visit patients. Curious for those outside the initial focus, what the key points of education are to drive uptake and whether that differs US versus ex-US. Maybe second question on the early-stage pipeline. Curious if there has been any change to your development plans in PKU after the approval of PTC's second.

Marc Frahm: Hey, guys. This is Matthew Wong for Alec Stranahan. Thanks for taking our question. Maybe first from us, I know the initial focus of the launch is on higher frequency of visit patients. Curious for those outside the initial focus, what the key points of education are to drive uptake and whether that differs U.S. versus ex-U.S. Then maybe a second question on the early-stage pipeline. Curious if there has been any change to your development plans in PKU after the approval of PTC's second.

Our next question comes from the line of Alec Stranahan with Bank of America. Your line is open. Please go ahead.

Hey, guys. This is Matthew on for Alex. Thanks for taking my question, maybe first from us.

I know the initial focus of the launches on higher frequency.

Visit patients curious for those outside the initial focus what the key points of education of our to drive uptake and whether that differs.

Us versus ex U S.

And then maybe a second question on the early stage pipeline I'm curious if there's been any change to your development plans in PKU.

Brian Goff: Okay. Thanks, Matthew. Sveta can start on the question about beyond the initial higher frequency clinical touch points, what does segmentation look like?

Brian Goff: Okay. Thanks, Matthew. Tsveta can start on the question about beyond the initial higher frequency clinical touchpoints, what does segmentation look like?

Brian Goff: Thanks, Matthew. Tsveta Milanova can start on the question about beyond the initial higher frequency clinical touchpoints, what does segmentation look like?

After the approval of our PTC use.

Yes.

Okay. So thanks, Matthew so aesthetic can start on the question about beyond the initial <unk>.

Tsveta Milanova: Absolutely. As we said, our priority segments are patients that are transfusion-dependent or non-transfusion-dependent patients that require additional management because of their symptoms of the disease. When we look beyond that patient segments, we'll continue to expand into the non-transfusion-dependent patients who might be experiencing symptoms but might not be ready to initiate therapy immediately. It's also important for us to remember that as patients age, the burden of their disease increases, so they might be actually developing complications of the disease as well. The key educational elements there will continue to be remain the same. We know that the unmet need in thalassemia is well characterized, but it is also an evolving field, and additional data on the unmet need, especially in the non-transfusion-dependent patients, is emerging.

Sarah Gheuens: Absolutely. As we said, our priority segments are patients that are transfusion-dependent or non-transfusion-dependent patients that require additional management because of their symptoms of the disease. When we look beyond that patient segment, we will continue to expand into the non-transfusion-dependent patients who might be experiencing symptoms but might not be ready to initiate therapy immediately. It is also important for us to remember that as patients age, the burden of their disease increases, so they might be actually developing complications of the disease as well. The key educational elements there will continue to remain the same. We know that the unmet need in thalassemia is well-characterized, but it is also an evolving field, and additional data on the unmet need, especially in the non-transfusion-dependent patients, is emerging.

Higher frequency clinical touch points with the segmentation look like.

Absolutely. So as we said our priority segments are patients that are transfusion dependent or non transfusion dependent patients that require additional management because of their symptoms of the disease. When we look beyond that patient segments will continue to expand into the non transfusion dependent patients.

Who might be experiencing symptoms, but might not be ready to initiate therapy immediately.

Also important for us to remember that as patients age the burden of their disease in Korea, they still they might be actually developing complications of the disease as well the key educational elements. There will continue to be remain the same we know that the unmet need entellus EMEA is well characterized.

Tsveta Milanova: A lot of our educational efforts are actually disseminating that additional information and continuing to engage both with patients and physicians. We're also stressing the importance of continuous monitoring for those patients, given the long-term disease complications and the pathophysiology of the disease, which is an important element for us. Once we are ready to expand, we'll have more engaged both patients and physician community on that front. That will be consistent in the US and ex-US, of course. Our priority and segmentation across the globe will remain quite consistent. However, ex-US will need to deal with different market access dynamics and patient access, which we'll address with our partners appropriately on a country-by-country basis.

Sarah Gheuens: A lot of our educational efforts are actually disseminating that additional information and continue to engage both with patients and physicians. We are also stressing the importance of continuous monitoring for those patients, given the long-term disease complications and the pathophysiology of the disease, which is an important element for us. Once we are ready to expand, we will have more engaged both patient and physician community on that front. That will be consistent in the U.S. and ex-U.S., of course. Our priority and segmentation across the globe will remain quite consistent. However, ex-U.S. will need to deal with different market access dynamics and patient access, which we will address with our partners appropriately on a country-by-country basis.

But it is also an evolving field and additional data on the unmet need, especially in the non transfusion dependent patients is emerging so a lot of our educational efforts are actually disseminated.

Disseminating that additional information I'm continuing to engage both with patients and physicians were also stressing the importance of continuous monitoring for those patients.

Given the the long term disease complications in the pathophysiology of the disease, which is an important element for us.

So once we are ready to expand it we'll have more engaged both patient and physician community on that front.

That'll be consistent in the U S and ex U S of course the.

The our priority on segmentation across the globe.

All remain quite consistent.

All of our ex U S will need to deal with different market access dynamics and patient access, which will want the rest with our partner it's appropriately on a country by country basis, and just as a point of emphasis to <unk> point about ex U S. We're really clear on the geographic priorities U S. Clearly is our number one priority and Thats why you spend on the team.

Brian Goff: Just as a point of emphasis to Sveta's point about ex-US, we're really clear on the geographic priorities. US clearly is our number one priority, and that's why Sveta and the team have designed for direct commercialization. We're really proud of the partnerships that we have already established and updated, in fact, this morning with Europe with Avanzanite Bioscience as well as NewBridge in GCC. As I noted, that's a very capital efficient approach, but it also leans on localized expertise in those geographies accordingly. Then to the second question about PKU, maybe I'll have Sarah pick up on that.

Brian Goff: Just as a point of emphasis to Tsveta Milanova's point about ex-U.S., we are really clear on the geographic priorities. U.S. clearly is our number one priority, and that is why Tsveta Milanova and the team have designed for direct commercialization. We are really proud of the partnerships that we have already established and updated, in fact, this morning with Europe, with Advansanite Biosciences, as well as Newbridge in GCC. As I noted, that is a very capital-efficient approach, but it also leans on localized expertise in those geographies accordingly. To the second question about PKU, maybe I will have Sarah Gheuens pick up on that.

Brian Goff: Just as a point of emphasis to Tsveta Milanova's point about ex-U.S., we are really clear on the geographic priorities. U.S. clearly is our number one priority, and that is why Tsveta Milanova and the team have designed for direct commercialization. We are really proud of the partnerships that we have already established and updated, in fact, this morning with Europe, with Advansanite Biosciences, as well as Newbridge in GCC. That is, as I noted, a very capital-efficient approach, but it also leans on localized expertise in those geographies accordingly. To the second question about PKU, maybe I will have Sarah Gheuens pick up on that.

<unk> designed.

For direct commercialization and we're really proud of the partnerships that we have already established and.

And updated in fact this morning with.

Europe with <unk> Biosciences, as well as new bridge in GCC and Thats as I noted that is a very capital efficient approach, but it also leans on localized expertise in those geographies accordingly.

Sarah Gheuens: Yes. We have not made any changes based on the recent approval. We are very excited about that approval to be able to monitor what happens and of course, learn from them as well as they progress. Fundamentally, the same principles around our program remain intact because we have a drug, a phenylalanine hydroxylase stabilizer, basically, which is completely a novel mechanism of action, oral therapy with the potential to really deliver another therapy to patients who still have a dire need. Even with this recent approval, there will remain a dire need for other options because these patients, they can be in the position that they don't respond to the therapies or they have, you know, if you think about PALYNZIQ, there may be anaphylaxis or things like that.

Sarah Gheuens: Yes. So we have not made any changes based on the recent approval. We are very excited about that approval to be able to monitor what happens and, of course, learn from them as well as they progress. But fundamentally, the same principles around our program remain intact because we have a drug, a phenylalanine hydroxylase stabilizer, basically, which is completely a novel mechanism of action, oral therapy with the potential to really deliver another therapy to patients who still have a dire need. Even with this recent approval, there will remain a dire need for other options because these patients, they can be in the position that they do not respond to the therapies, or they have, if you think about Pyrukynd, there may be anaphylaxis or things like that. So there will remain a big, big gap there to address.

Sarah Gheuens: Yes. We have not made any changes based on the recent approval. We are very excited about that approval to be able to monitor what happens and, of course, learn from them as well as they progress. But fundamentally, the same principles around our program remain intact because we have a drug, a phenylalanine hydroxylase stabilizer, basically, which is completely a novel mechanism of action, oral therapy with the potential to really deliver another therapy to patients who still have a dire need. Even with this recent approval, there will remain a dire need for other options because these patients, they can be in the position that they do not respond to the therapies, or they have, if you think about palimpsic, there may be anaphylaxis or things like that. So, there will remain a big, big gap there to address.

And then to the second question about PKU, maybe I'll have Sarah pickup on that yes. So.

So we have not made any changes based on the recent approval. We are very excited about that approval to be able to monitor what happens in Europe.

Learn from them as well as the day progressed, but.

Italy.

The same principles around our program remain in fact, because we have a drug or a single alanine hydroxylase stabilizer basically which is completely novel mechanism of action oral therapy with the potential to really deliver another therapy to patients who still have a dire need even with its recent approval there will remain a <unk>.

Dire dire.

Dire need for other options because these patients they are.

It can be in the position that they don't respond to the therapies or they have you know if you think about our balance sheet, there may be anaphylaxis or things like that so there will remain a big big gap there to do it.

Sarah Gheuens: There will remain a big gap there to address. You even see that reflected in the current label that they received on the new drug because the stopping criteria when there is no treatment response observed means that there effectively will be people who are not responding to this therapy and will need other options.

Sarah Gheuens: You even see that reflected in the current label that they received on the new drug because the stopping criteria when there is no treatment response observed means that there effectively will be people who are not responding to this therapy and will need other options.

Dressed.

Even see that reflected in the current label that they received.

The new drug because the stopping criteria when there is no treatment response observed.

Brian Goff: PKU is right in the sweet spot for Agios as a company that takes a lot of pride in innovation to address diseases with high unmet needs. Just like across thalassemia, sickle cell, PKD, any of our diseases that we're pursuing, any innovation is important. You know, we like to read that news that you referred to, and we're very excited about the progress that we're making with our own phenylalanine hydroxylase stabilizer with AG-181. Thanks a lot.

Brian Goff: PKU is right in the sweet spot for Agios Pharmaceuticals as a company that takes a lot of pride in innovation to address diseases with high unmet needs. Just like across thalassemia, sickle cell, PKD, any of our diseases that we are pursuing, any innovation is important. We like to read that news that you referred to, and we are very excited about the progress that we are making with our own pH hydroxylase stabilizer with 1A1. Thanks a lot.

Means that they are effectively will be people, who are not responding to this therapy, but we need other options.

In PKU is right in the sweet spot for our Geos.

A company that takes a lot of pride in.

Innovation to address diseases with high unmet need so just just like across thalassemia sickle cell <unk> heard diseases that we're pursuing any innovation is important and.

We would like to read that news that you referred to and we're very excited about the progress that we're making with <unk>.

Our own.

Operator: Thank you. One more moment as we move on to the next question. Our next question is going to come from the line of Andrew Berens with Leerink Partners. Your line is open. Please go ahead.

Operator: Thank you. One moment as we move on to the next question. Our next question is going to come from the line of Andrew Burns with Lerink Partners. Your line is open. Please go ahead.

Hydroxylase stabilizer with 181.

So thanks a lot.

Thank you and one moment as we move on to the next question.

Andrew Berens: Hi, thanks, and congrats on all the progress. This is a follow-up to Marc's earlier question. Has anything changed in the sickle cell trial protocol since you identified risks in liver injury at ASH 2024? Interested in whether the consent forms and the monitoring requirements have changed. Then I have one on tebapivat. We noticed that the tebapivat trial is using markedly lower doses than the MDS phase 2B trials being conducted. Can you discuss the dosing protocol in this trial and the rationale for going lower in the sickle cell trial? Are there data at the relevant doses in MDS and sickle cell that you can share with us? Hello?

Emily Bodner: Hi. Thanks, and congrats on all the progress. This is a follow-up to Marc Frahm's earlier question. Has anything changed in the sickle cell trial protocol since you identified the risks in liver injury at ASH 2024? Interested in whether the consent forms and the monitoring requirements have changed. I have one on tebapivat. We noticed that the tebapivat trial is using markedly lower doses than the MDF phase 2B trial is being conducted. Can you discuss the dosing protocol in this trial and the rationale for going lower in the sickle cell trial? Are there data at the relevant doses in MDF and sickle cell that you can share with us? Hello?

Our next question is going to come from the line of Andrew Burns with Leerink Partners. Your line is open. Please go ahead.

Alright, thanks, and congrats on all the progress.

Just as a follow up sort of Mark's earlier question.

Has anything changed in the sickle cell trial protocol since you identified risks.

<unk> and liver injury of Ash 2024 interested in whether the consent forms and the monitoring requirements.

Change and then I have one on tablets that we noticed that the cover to that trial was is a markedly lower doses than the Mds phase <unk> trial is being conducted can you discuss the dosing protocol and the <unk>.

While on the rationale for going lower in the sickle cell trial are there data relevant doses in MBS in sickle cell that you can share with us.

Sarah Gheuens: Yeah, okay. So, in regards to the sickle cell disease protocol, we have announced in the past that once we identified this risk in the thalassemia program, that we had aligned all of our protocols to have monthly monitoring for the first six months, so including our open label extension trial. For the sickle cell disease protocol, we aligned the open label extension study to match what happened in the first part of the randomized control trial because obviously, placebo patients get exposed for the first time in the open label extension study. So, we made sure that they had the same type of monitoring. That is effectively reflected in the protocols, and we did update those informed consents as well, obviously. In regards to your next question around the dosing differences between the sickle cell disease phase 2 and the MDF phase 2B, you are right.

Sarah Gheuens: Yeah, okay. In regards to the sickle cell disease protocol, we've announced in the past that once we identified this risk in the thalassemia program, we had aligned all of our protocols to have monthly monitoring for the first 6 months. Including our open label extension trial. For the sickle cell disease protocol, we aligned the open label extension study to match what happens in the first part of the randomized controlled trial. Because, obviously, placebo patients get exposed for the first time in the open label extension study. We made sure that they have the same type of monitoring. That is effectively reflected in the protocols. We did update those informed consents as well, obviously.

Hello.

Yes, okay.

So in regards to the sickle cell disease protocol, we've announced in the past the ones we identified.

Risk in the <unk> program that we have aligned all of our protocols to have monthly monitoring for the first six months, so including our open label extension trial, so far the sickle cell disease protocol, we aligned the open label extension study to match what happens in the first part of the randomized control trial because obviously.

Placebo patients get exposed for the first time in the open label extension study. So we made sure that they have the same type of monitoring and so that is effectively reflected in the protocols and this update those informed consents.

Sarah Gheuens: In regards to your next question around the dosing differences between the sickle cell disease phase 2 and the MDS phase 2B, you are right. We are exploring lower doses within the sickle cell disease phase 2, and that is because the sickle cell disease patients, their metabolism matches the healthy volunteer metabolism that was observed in the phase 1. Reminder that we had sickle cell disease patients included in that trial as well. We have that. In the MDS trial, in the 2A, we observed that the MDS patients metabolize the drug faster, so we adapted to the doses appropriately. That's why we are exploring different doses between sickle cell disease and MDS.

Well, obviously and.

And in regards to your next question around the dosing differences between the sickle cell disease phase II in the Mds phase two b.

Sarah Gheuens: We are exploring lower doses within the sickle cell disease phase 2, and that is because the sickle cell disease patients, their metabolism matches the healthy volunteer metabolism that was observed in the phase 1. Reminder that we had sickle cell disease patients included in that trial as well, so we have that. But then in the MDF trial in the 2A, we observed that the MDF patients metabolize the drug faster, so we adapted the doses appropriately. That's what you will see that we are exploring. That's why we are exploring different doses between sickle cell disease and MDF.

You are right, we are exploring a lower lower doses within the sickle cell disease phase two and that is because the sickle cell disease patients their.

Apple Ism matches the healthy volunteer.

Metabolism that was observed in the phase One reminder, that we have sickle cell disease patients included in that trial as well so we have to have it.

The Mds trial in the two <unk>, we observed that the Mds patients with <unk> have dropped faster. So we adapted the dose appropriately and so thats what.

Andrew Berens: Thanks.

Brian Goff: Thanks, Sarah.

You'll see that we are exploring that's why we are exploring different doses of between sickle cell disease in EMEA.

Brian Goff: Thanks, sir.

Andrew Berens: Thank you.

Emily Bodner: Thank you.

Operator: Thank you. One moment for our next question. Our next question is going to come from the line of Tessa Romero with J.P. Morgan. Your line is open. Please go ahead.

Thanks, Sir thank you.

Thank you and one moment for our next question.

Tessa Romero: Good morning, Brian and team. Thanks for taking our question. To double-click back on a few of the earlier questions on the call, is it still reasonable to assume that the potential risk of hepatocellular injury will sit in the warnings and precautions sections of the label, as is currently reflected today? Relatedly, when do you expect to present your open label extension data that you have collected in this population that may be of interest to physicians and institutions as they begin to prescribe in thalassemia? Thank you.

Tessa Romero: Good morning, Brian and team. Thanks for taking our question. To double-click back on a few of the earlier questions on the call, is it still reasonable to assume that the potential risk of hepatocellular injury will sit in the warnings and precautions sections of the label as is currently reflected today? Relatedly, when do you expect to present your open label extension data that you have collected in this population that may be of interest to physicians and institutions as they begin to prescribe in thalassemia? Thank you.

Our next question is going to come from the line of Tessa Romero with Jpmorgan. Your line is open. Please go ahead.

Yeah.

Good morning, Brian and team Thanks for taking our question.

So to that real quick back on a few of the earlier questions on the call.

Is it still reasonable to assume that the potential risk of hepatic <unk> and dream will sit in the warnings and precautions section of the label.

As is currently reflected today and Relatedly when do you expect to present your open label extension data that you have collected in this population that may be of interest to physicians and institutions as they begin to prescribe in Dallas EMEA. Thank you.

Brian Goff: Sure. Thanks, Tess. Sarah can take both of those. I'll just say on the open label extension, we're also interested in the data, of course, but we're gonna do things sequentially.

Brian Goff: Sure. Thanks, Tess. Sarah can take both of those. I will just say on the open label extension, we are also interested in the data, of course, but we are going to do things sequentially.

Sure. Thanks to start can take both of those I will just say on the open label extension where also interest.

Sarah Gheuens: Yes. Or maybe I can start actually with that one. On the open label extension, you'll see us publish data of the open label extensions like we always do, just like what we've done for PKD. Obviously, right now we're very focused on our ongoing reviews and prioritize the time of the teams there versus trying to get more publications out on the extension data. That's coming for sure. We share that interest, obviously. You're right, everybody will continue to be interested in that. More to come. In regards to your question around HCI and where it sits in the label, Brian mentioned it earlier. Obviously, we continue to engage with the agency as it goes. The benefit risk review is still ongoing with the agency.

Sarah Gheuens: Yes, or maybe I can start actually with that one. On the open label extension, you will see us publish data of the open label extensions like we always do, just like what we have done for PKD. Obviously, right now we are very focused on our ongoing reviews and prioritize the time of the teams there versus trying to get more publications out on extension data. But that is coming for sure. We share that interest, obviously. You are right, everybody will continue to be interested in that. So more to come. Then in regards to your question around HCI and where it sits in the label, Brian Goff mentioned it earlier. Obviously, we continue to engage with the agency as it goes. The benefit-risk review is still ongoing with the agency.

The data of course, but we're going to do things sequentially.

Yes, maybe I can start is actually not one like on the open label extension that Youll see US published data. The open label extensions like we always do just like what we've done for P. J P. Obviously right now we're <unk>.

Very focused on our ongoing reviews and prioritize the time of the teams there versus trying to get more publications out on the extension data, but that's coming for sure we share that interest obviously.

And Youre right, but everybody will continue to be interested in that flow.

I want to come and then in regards to your question around HCI and where it sits in the label Brian mentioned it earlier, obviously, we are we continue to engage with the agency as it as it goes like the benefit risk review is still ongoing with the agency I think right now what you see.

Sarah Gheuens: I think right now what you see, what is reflected in the PKD label to date is what we have observed in our program, right? Which is you can see that language in another condition, another higher dose is in the warning and precaution section of the PKD label. That language has to be updated at some point when we get to the final label for thalassemia. In regards to where it would end up or what would change, we do not comment on ongoing review processes with the agency. But as you know, our PDUFA date is September 7th, at which point the procedure should be completed. Then we will all have the final label and can talk more about that.

Sarah Gheuens: I think right now what you see, what is reflected in the PKD label, to date is what we have observed in our program, right? Which is, you can see that language in another condition and at a higher dose is in the warning and precaution section of the PKD label. That language has to be updated at some point when we get to the final label for thalassemia. In regards to where it would end up or what would change, we don't comment on ongoing review processes with the agency. As you know, our PDUFA date is December 7, at which point the procedure should be completed and then we will all have the final label and can talk more about that.

Just what is reflected in the <unk> label.

To date is what we have observed in our program right, which is.

You can see that language in another condition. Another a higher adults is in the warnings and precautions section of the <unk> label.

That language has to be uptick.

When we get to the final label for <unk> in regards to.

Where it would end up or what would change I mean, we don't comment on ongoing review processes with the agency, but as you know our paducah.

Seven at which point the procedure should be completed and then you can we will all have the final labeling.

Operator: Thank you. Thank you. Our final question is going to come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

Operator: Thank you. Thank you. Our final question is gonna come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

Tessa Romero: Thank you.

Can talk more about that.

Operator: Thank you. Our final question is gonna come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

Okay.

Yeah.

Thank you.

Yeah.

[Analyst] (Scotiabank): Good morning. This is Theresa on for Greg. Thanks for taking our question. Just wanted to see ahead of the launch, potential launch in thalassemia, if you could provide any additional color on the prescriber base for your initial launch focus and how you're planning to address any variability in care between academic centers and community hematologists.

Tessa Romero: Good morning. This is Tessa Romero on for Greg Harrison. Thanks for taking our question. I just wanted to see ahead of the launch, potential launch in thalassemia, if you could provide any additional color on the prescriber base for your initial launch focus and how you are planning to address any variability in care between academic centers and community hematologists.

Thank you and our final question is going to come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

Good morning. This is Teresa so Greg thanks for taking our question.

Just wanted to see how does the launch potential launch in thalassemia, you could provide any additional color on the prescriber base for your initial launch focus in.

Brian Goff: Yeah, thanks, Tessa Romero. Tsveta Milanova can maybe reiterate a few of the points we talked about earlier in terms of in the U.S., the 4,000 patients that are in our addressable target, and add a little bit more on community versus academic.

Brian Goff: Yeah. Thanks, Theresa. If Sarah can, maybe reiterate a few of the points we talked about earlier in terms of in the US, the 4,000 patients that are, you know, our addressable target, and add a little bit more on community versus academic.

How you're planning to address any variability and care between academic centers and community intelligence.

Yes, Thanks, Teresa Southern Ken.

Let me reiterate a few of the points, we talked about earlier in terms of in the U S. The 4000 patients that are <unk>.

Tsveta Milanova: Yeah. Absolutely. Theresa, as I mentioned, in the US, we really benefit from the fact that thalassemia patients are diagnosed, and they are well-established ICD-10 codes. We have a lot of clarity of where these patients are currently being treated and managed. In addition to that, the team has been really focused on a very robust launch preparations where we had the opportunity to connect with the prescriber base and profile the accounts and really prioritize them appropriately based on the patients that they have, and their potential willingness to manage these patients further. Of course, majority of the transfusion-dependent patients are actually within the academic centers, where you would see a little bit more penetration in the transfusion-dependent setting.

Sarah Gheuens: Yeah. Absolutely. Theresa, as I mentioned, in the US, we really benefit from the fact that thalassemia patients are diagnosed, and they are well-established ICD-10 codes. We have a lot of clarity of where these patients are currently being treated and managed. In addition to that, the team has been really focused on a very robust launch preparations where we had the opportunity to connect with the prescriber base and profile the accounts and really prioritize them appropriately based on the patients that they have, and their potential willingness to manage these patients further. Of course, majority of the transfusion-dependent patients are actually within the academic centers, where you would see a little bit more penetration in the transfusion-dependent setting.

Sarah Gheuens: Absolutely. So, Theresa, as I mentioned, in the U.S., we really benefit from the fact that thalassemia patients are diagnosed and there are well-established ICD-10 codes. So, we have a lot of clarity of where these patients are currently being treated and managed. In addition to that, the team has been really focused on a very robust launch preparation where we had the opportunity to connect with the prescriber base and profile the account and really prioritize them appropriately based on the patients that they have and their potential willingness to manage these patients further. Of course, the majority of the transfusion-dependent patients are actually within the academic centers where you see a little bit more penetration in the transfusion-dependent setting. However, there is a very high unmet need in the non-transfusion-dependent patients, and that need is very well characterized and understood.

Addressable target anatomy.

And add a little bit more on community versus academic.

Absolutely. So there is as I mentioned in the U S. We really benefit from the fact that the leukemia patients are diagnosed and theyre well established ICD 10 codes. So we have a lot of clarity of where these patients are currently being treated and managed.

In addition to that the team has been really focused on a very robust launch preparations, where we had the opportunity to connect with the prescriber base and profiled that counts.

And really.

<unk> prioritized them appropriately based on the patients that have they have and their potential willingness to manage these patients are there.

Of course majority of the transfusion dependent patients are actually within the banking centers, where you will see a little bit more penetration in the transfusion dependent setting. However, there is a very high unmet need in the non transfusion dependent patients.

Tsveta Milanova: However, there is a very high unmet need in the non-transfusion dependent patients, and that need is very well characterized and understood. Even though if some of these patients are managed in the community, we've been able to actually engage with those prescribers, identify where these patients are managed, provide disease education, and prioritize those accounts, so we can pull them through launch as well at the beginning of the launch.

Sarah Gheuens: However, there is a very high unmet need in the non-transfusion dependent patients, and that need is very well characterized and understood. Even though if some of these patients are managed in the community, we've been able to actually engage with those prescribers, identify where these patients are managed, provide disease education, and prioritize those accounts, so we can pull them through launch as well at the beginning of the launch.

Sarah Gheuens: Even though some of these patients are managed in the community, we've been able to actually engage with those prescribers, identify where these patients are managed, provide disease education, and prioritize those accounts so we can pull them through launch as well at the beginning of the launch.

And that Netease is a very well characterized and understood even though some of these patients are managed in the community.

We've been able to actually engage with those prescribers indentified. What are these patients that are managed to provide disease education and prioritize those accounts. So we can for them to go launch as well at the beginning of the launch.

Operator: Thank you. I would like to hand the conference back over to Brian Goff for any further remarks.

Okay.

Brian Goff: Okay, thanks, Michelle, and thank you very much everyone for participating in today's call. As you know, we're halfway through yet another busy year. It's a very exciting time at Agios, and we truly believe that we are poised to deliver transformative new therapies for patients and to create significant long-term value to shareholders. Thanks again, and we look forward to speaking with you again soon.

Brian Goff: Okay, thanks, Michelle. Thank you very much, everyone, for participating in today's call. As you know, we are halfway through yet another busy year. It is a very exciting time at Agios Pharmaceuticals, and we truly believe that we are poised to deliver transformative new therapies for patients and to create significant long-term value to shareholders. Thanks again, and we look forward to speaking with you again soon.

Thank you and I would like to hand, the conference back over to Brian Goff for any further remarks.

Okay. Thanks, Michelle and thank you very much everyone for participating in today's call.

As you know we're halfway through yet another busy year, it's a very exciting time at <unk> and we truly believe that we are poised to deliver transformative new therapies for patients.

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

And to create significant long term value to shareholders. So thanks, again, and we look forward to speaking with you again soon.

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

Okay.

[music].

Yes.

[music].

Okay.

[music].

Okay.

[music].

Q2 2025 Agios Pharmaceuticals Inc Earnings Call

Request a DemoDemo

AGIO

Agios Pharmaceuticals

Earnings