Q2 2026 Agios Pharmaceuticals Inc Earnings Call

July 30, 2026

Speaker #2: Good morning, and welcome to Agios Pharmaceuticals’ Q2 2026 conference call. At this time, all participants are in listen-only mode. There will be a question-and-answer session at the end.

Operator: Good morning, and welcome to Agios Pharmaceuticals' Q2 2026 conference call. At this time, all participants are in 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 Morgan Sanford, Head of Investor Relations at Agios.

Speaker #2: Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Morgan Sanford, Head of Investor Relations at Agios.

Speaker #3: Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' Q2 2026 financial results and business highlights. You can access the slides for today's call by going to the Investors section of our website, agios.com.

Morgan Sanford: Thank you, operator. Good morning, everyone. Thank you for joining us to discuss Agios Pharmaceuticals' Q2 2026 financial results and business highlights. You can access the slides for today's call by going to the Investors section of our website, agios.com. Please note we'll be making certain forward-looking statements today. Actual events and results could differ materially from those expressed or implied by any forward-looking statements because of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the SEC, and any other future filings that we may make with the SEC. 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. Sarah Gheuens, Chief Medical Officer and Head of Research and Development. Following prepared remarks, we will open the call for questions.

Speaker #3: Please note we'll be making certain forward-looking statements today. Actual events and results could differ materially from those expressed or implied by any forward-looking statements because of various risks, uncertainties, and other factors including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC.

Speaker #3: 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. Sarah Gheuens, Chief Medical Officer and Head of Research and Development.

Speaker #3: Following prepared remarks, we will open the call for questions. With that, I am pleased to turn the call over to Brian.

Morgan Sanford: With that, I am pleased to turn the call over to Brian.

Speaker #4: Thanks, Morgan. Good morning, everyone, and thank you for joining us. Before we review our Q2 results, I'd like to take a step back and highlight the strong position from which Agios is executing as we continue advancing toward our goal of building a multibillion-dollar rare disease business.

Brian Goff: Thanks, Morgan. Good morning, everyone, and thank you for joining us. Before we review our Q2 results, I'd like to take a step back and highlight the strong position from which Agios is executing as we continue advancing toward our goal of building a multibillion-dollar rare disease business. We are executing against multiple drivers of value creation, including the launch of AQVESME in thalassemia, the potential expansion of mitapivat into sickle cell disease, and a pipeline that continues to grow through both internal innovation and disciplined business development. During the quarter, we further strengthened our portfolio with the addition of cevidoplenib, a next-generation, highly selective oral Syk inhibitor that expands our rare hematology franchise into immune thrombocytopenia, or ITP. We also advanced AG-236 into an operationally seamless phase II/III program in polycythemia vera, adding another potential growth driver within hematology.

Speaker #4: We are executing against multiple drivers of value creation, including the launch of ACVESMI and thalassemia, the potential expansion of midepivet into sickle cell disease, and a pipeline that continues to grow through both internal innovation and discipline business development.

Speaker #4: During the quarter, we further strengthened our portfolio with the addition of sevedoclinib, a next-generation highly selective oral sick inhibitor that expands our rare hematology franchise into immune thrombocytopenia or ITP.

Speaker #4: We also advanced AG236 into an operationally seamless Phase II/III program in polycythemia vera, adding another potential growth driver within hematology. Beyond hematology, AG181 continues to progress, and we expect Phase IB proof-of-mechanism data in phenylketonuria patients in the second half of the year.

Brian Goff: Beyond hematology, AG-181 continues to progress, and we expect phase I-B proof of mechanism data in phenylketonuria patients in H2 of the year. We also continue to apply a disciplined approach to portfolio management, making focused investment decisions and directing resources toward opportunities with the greatest potential to create value for patients and shareholders. As you'll hear throughout today's call, our progress this quarter reflects the strength of that strategy, combining commercial execution, pipeline advancement, disciplined capital allocation, and strategic business development to position Agios for sustainable long-term growth. Turning to our Q2 highlights on the next slide, we delivered a quarter marked by strong commercial performance, meaningful pipeline progress, and continued portfolio discipline. First, we delivered sustained commercial momentum with $44.7 million in total net revenue, including $40.9 million in the US and 442 cumulative AQVESME prescriptions from REMS-certified physicians.

Speaker #4: We also continue to apply a disciplined approach to portfolio management, making focused investment decisions and directing resources toward opportunities with the greatest potential to create value for patients and shareholders.

Speaker #4: As you'll hear throughout today's call, our progress this quarter reflects the strength of that strategy. Combining commercial execution, pipeline advancement, discipline capital allocation, and strategic business development to position AGIOS for sustainable long-term growth.

Speaker #4: Turning to our Q2 highlights on the next slide, we delivered a Q2 marked by strong commercial performance meaningful pipeline progress and continued portfolio discipline.

Speaker #4: First, we delivered sustained commercial momentum with 44.7 million dollars in total net revenue including 40.9 million dollars in the US and 442 cumulative ACVESMI prescriptions from REM-certified physicians.

Speaker #4: Second, we further diversified our pipeline through the in-licensing of sevedoclinib, a next-generation, highly selective oral SYK inhibitor for ITP, progressing toward Phase III and strengthening our rare hematology pipeline.

Brian Goff: Second, we further diversified our pipeline through the in-licensing of cevidoplenib, a next-generation, highly selective oral Syk inhibitor for ITP, progressing toward phase III and strengthening our rare hematology pipeline. Third, we advanced mitapivat toward a potential new indication in sickle cell disease. During the quarter, we received FDA acceptance of our sNDA with priority review and were assigned a PDUFA goal date of 1 November, bringing us one step closer to delivering a first-in-class medicine in an area of significant unmet need. Finally, we ended the quarter with approximately $1 billion in cash equivalents, and marketable securities, providing financial flexibility to support both commercial growth and pipeline progression. Overall, we entered H2 2026 with strong commercial delivery, a more diversified pipeline, an important near-term regulatory catalyst, and the capital position to execute on our strategy.

Speaker #4: Third, we advanced midepivet toward a potential new indication in sickle cell disease. During the quarter, we received FDA acceptance of our SNDA with priority review, and were assigned a PDUFA goal date of November 1, bringing us one step closer to delivering a first-in-class medicine in an area of significant unmet need.

Speaker #4: And finally, we ended the quarter with approximately 1 billion dollars in cash, cash equivalents in marketable securities, providing financial flexibility to support both commercial growth and pipeline progression.

Speaker #4: Overall, we entered the second half of 2026 with strong commercial delivery, a more diversified pipeline, and important near-term regulatory catalysts, and the capital position to execute on our strategy.

Speaker #4: With that, please advance to the next slide, and I'll turn the call over to Cecilia to discuss financials.

Brian Goff: With that, please advance to the next slide, and I'll turn the call over to Cecilia to discuss financials.

Speaker #3: Thank you, Brian. Next slide, please. Turning to our Q2 financial results, total mitapivat net revenue was $44.7 million, including $40.9 million in the US and $3.8 million outside the US.

Cecilia Jones: Thank you, Brian. Next slide, please. Turning to our Q2 financial results, total mitapivat net revenue was $44.7 million, including $40.9 million in the US and $3.8 million outside the US. Cost of sales for the quarter was $3 million, and research and development expense was $100.8 million compared to $91.9 million in Q2 2025, primarily due to an increase in in-process research and development of $15 million, driven by the $25 million upfront payment associated with the agreement of Oscotec. Selling, general, and administrative expense was $61.5 million compared to $45.9 million in the prior year period, reflecting an increase in commercial-related activities as we executed our launch of AQVESME in thalassemia. Net loss for Q2 2026 was $100.7 million compared to a net loss of $112 million for Q2 2025.

Speaker #3: Cost of sales for the quarter was 3 million dollars, and research and development expense was 100.8 million dollars, compared to 91.9 million dollars in the Q2 of 2025.

Speaker #3: Primarily due to an increase in processed research and development of $15 million, driven by the $25 million upfront payment associated with the agreement of offsets.

Speaker #3: Selling, general, and administrative expense was $61.5 million, compared to $45.9 million in the prior-year period, reflecting an increase in commercial-related activities as we execute our launch of AG-946 and thalassemia.

Speaker #3: Net loss for the Q2 of 2026 was 100.7 million dollars, compared to a net loss of 112 million dollars for the Q2 of 2025.

Speaker #3: We ended the quarter with approximately $1 billion in cash, cash equivalents, and marketable securities, which we believe provides financial flexibility to support commercial execution, advancement of our pipeline, and continued investment in opportunities to create long-term value.

Cecilia Jones: We ended the quarter with approximately $1 billion in cash equivalents, and marketable securities, which we believe provides financial flexibility to support commercial execution, advancement of our pipeline, and continued investment in opportunities to create long-term value. Turning to our outlook for 2026, we continue to expect approximately $45 to $50 million from PK deficiency revenues in the US. Full-year operating expenses are expected to remain approximately flat versus 2025, excluding the $25 million upfront payments associated with the cevidoplenib licensing transaction recognized in Q2 and include investments to prepare for a potential sickle cell disease launch aligned with our 1 November PDUFA date. Our priorities for the remainder of the year remain clear: driving the AQVESME launch, preparing for a potential sickle cell disease approval, advancing our pipeline, and maintaining financial discipline.

Speaker #3: Turning to our outlook for 2026, we continue to expect approximately 45 to 50 million dollars from PK deficiency revenues in the US. Full-year operating expenses are expected to remain approximately flat versus 2025, excluding the 25 million dollar upfront payment associated with the sevedoclinib in-licensing transaction recognized in the Q2, and include investment to prepare for a potential sickle cell disease launch aligned with our November 1 PDUFA date.

Speaker #3: Our priorities for the remainder of the year remain clear. Driving the ACVESMI launch, preparing for a potential sickle cell disease approval, advancing our pipeline, and maintaining financial discipline.

Speaker #3: Please advance to the next slide, and I'll turn it over to Sarah to cover commercial highlights and ACVESMI US thalassemia launch progress.

Cecilia Jones: Please advance to the next slide, and I'll turn it over to Tsveta to cover commercial highlights and AQVESME US thalassemia launch progress.

Speaker #5: Thanks, Cecilia. Next slide, please. With six months of launch experience now behind us, we're encouraged by the underlying drivers of performance. What we have seen so far continues to reinforce our confidence in the long-term ACVESMI opportunity in thalassemia.

Tsveta Milanova: Thanks, Cecilia. Next slide, please. With 6 months of launch experience now behind us, we're encouraged by the underlying drivers of performance. What we have seen so far continues to reinforce our confidence in the long-term AQVESME opportunity in thalassemia. Importantly, the strong execution across our commercial and patient-focused organization further strengthens our confidence in future launch opportunities. In the US, performance reflected continued growth in thalassemia demand and solid commercial execution. Net revenue in the quarter reflected approximately $5 million of one-time benefits related to stocking in thalassemia, along with modest gross-to-net favorability. We continue to expect gross to net within our previously guided 10% to 20% range with quarter-to-quarter variability. Outside the US, we delivered $3.8 million in net sales, reflecting anticipated demand for thalassemia in Europe following approval and continued consistent early demand for thalassemia in the GCC.

Speaker #5: Importantly, the strong execution across our commercial and patient-focused organizations further strengthened our confidence in future launch opportunities. In the US, performance reflected continued growth in thalassemia demand and solid commercial execution.

Speaker #5: Net revenue in Q2 reflected approximately $5 million of one-time benefits related to stocking in thalassemia, along with modest gross-to-net favorability. We continue to expect gross-to-net within our previously guided 10% to 20% range, with Q2 to Q2 variability.

Speaker #5: Outside the US, we delivered 3.8 million dollars in net sales reflecting anticipated demand for thalassemia in Europe following approval and continued consistent early demand for thalassemia in the GCC.

Speaker #5: As we have seen consistently across rare disease launches, the shape of new patient starts, naturally moderates as adoption broadens beyond the earliest wave of highly motivated patients and prescribers.

Tsveta Milanova: As we have seen consistently across rare disease launches, the shape of new patient starts naturally moderates as adoption broadens beyond the earliest wave of highly motivated patients and prescribers. We continue to expect quarter-to-quarter revenue variability reflecting order timing, inventory movement, and gross-to-net dynamics. Next slide, please. I'm very pleased with the continued US launch performance of AQVESME. During Q2, we generated an additional 200 prescriptions from REMS certified physicians, bringing cumulative prescriptions to 442 as of 30 June. As a reminder, this metric captures unique prescriptions for patients with completed START forms from REMS certified physicians and serves as an early indicator of underlying demand. Importantly, the underlying launch dynamics remain healthy. While demand continues to come from highly motivated patients.

Speaker #5: We continue to expect Q2 to Q2 revenue variability reflecting order timing, inventory movement, and gross-to-net dynamics. Next slide, please. I'm very pleased with the continued US launch performance of ACVESMI.

Speaker #5: During the Q2, we generated an additional 200 prescriptions from REM35 physicians bringing cumulative prescriptions to 442 as of June 30. As a reminder, these metrics captured unique prescriptions for patients with completed sparse forms from REM35 physicians and served as an early indicator of underlying demand.

Speaker #5: Importantly, the underlying launch dynamics remain healthy. While demand continued to come from highly motivated patients, we saw a growing proportion of non-transfusion-dependent patients in the Q2.

Tsveta Milanova: We saw a growing proportion of non-transfusion-dependent patients in the second quarter, a profile consistent with the therapy moving beyond the earliest, most motivated cohort of transfusion-dependent patients. We continue to see strong conversion from prescription to treatment initiation. Time-to-start is naturally trending toward our anticipated 10 to 12-week range as adoption broadens across the NTDT population, where treatment decisions often involve more deliberate clinical discussions and patients may have less frequent interactions with the healthcare system. Access continues to strengthen, and we now have approximately 75% of thalassemia lives covered under payer policy. Additionally, physician REMS certification continues to progress in step with prescribing activity, and it is not a barrier to patient access. As the launch matures, prescriptions with completed START forms become a less informative measure of performance. Whereas revenue increasingly reflects both new patient starts and persistence on therapy.

Speaker #5: A profile consistent with the therapy moving beyond the earliest, most motivated cohort of transfusion-dependent patients. We continue to see strong conversion from prescription to treatment initiation.

Speaker #5: Time to start is naturally trending toward our anticipated 10 to 12-week range as adoption broadens across the NTDT population, where treatment decisions often involve more deliberate, clinically discussions, and patients may have less frequent interactions with the healthcare system.

Speaker #5: Access continues to strengthen, and we now have approximately 75% of thalassemia lives covered under payer policies. Additionally, physician REM certification continues to progress in step with prescribing activity, and it's not a barrier to patient access.

Speaker #5: As the launch matures, prescriptions with completed SPARCs forms become a less informative measure of performance, whereas revenue increasingly reflects both new patient starts and persistence on therapy.

Speaker #5: For that reason, in anticipation of a potential FDA approval for me to pivot in sickle cell disease, we plan to discontinue reporting prescriptions from REM35 physicians after the Q3, and transition to revenue as our primary measure of commercial performance.

Tsveta Milanova: For that reason, in anticipation of a potential FDA approval for mitapivat in sickle cell disease, we plan to discontinue reporting prescriptions from REMS-certified physicians after Q3 and transition to revenue as our primary measure of commercial performance. Upon a potential sickle cell disease approval, we will assess the most meaningful metrics to communicate the progress and outlook of the broader mitapivat franchise. Next slide, please. I wanted to take a few moments to highlight thalassemia launch considerations in H2 of this year. H1 reflected a distinct initial phase of the launch. Q1 benefited from a strong pre-launch anticipation and momentum built in the period leading to approval following the more than 3-month PDUFA delay.

Speaker #5: Upon a potential sickle cell disease approval, we will assess the most meaningful metrics to communicate the progress and outlook of the broader MITAPIVOT franchise.

Speaker #5: Next slide, please. I wanted to take a few moments to highlight thalassemia launch considerations in the second half of this year. The first half reflected a distinct initial phase of the launch.

Speaker #5: The first Q2 benefited from a strong pre-launch anticipation and momentum built in the period leading to approval, following the more than three-month PDUFA delay.

Tsveta Milanova: Q2 demand continued to reflect adoption from highly motivated patients and prescribers. With time to treatment initiation beginning to approach our anticipated 10 to 12-week average at launch maturity. Looking ahead, we expect the shape of the launch to naturally evolve. Adoption is expanding into a broader non-transfusion-dependent population, where patients are typically seen less frequently and treatment decisions may take more time. As the patient mix continues to shift towards non-transfusion-dependent patients, we expect time to treatment initiation to move well within the 10 to 12-week range we consistently discussed. We are also mindful that the first cohort of patients who initiated therapy in the earliest month of launch is approaching 6 months of treatment, a natural point at which physicians assess clinical response.

Speaker #5: Q2 demand continued to reflect adoption from highly motivated patients and prescribers, with time to treatment initiation beginning to approach our anticipated 10- to 12-week average at launch maturity.

Speaker #5: Looking ahead, we expect the shape of the launch to naturally evolve. Adoption is expanding into a broader non-transfusion-dependent population, where patients are typically seen less frequently and treatment decisions may take more time.

Speaker #5: As the patient mix continues to shift toward non–transfusion-dependent patients, we expect time to treatment initiation to move well within the 10- to 12-week range we consistently discussed.

Speaker #5: We are also mindful that the first cohort of patients who initiated therapy in the earliest months of launch is approaching six months of treatment, a natural point at which physicians assess clinical response.

Speaker #5: This is an important part of the treatment journey, and it is the period during which we will begin to build a broader, real-world understanding of how physicians and patients evaluate response, and integrate that to pivot into long-term care.

Tsveta Milanova: This is an important part of the treatment journey, and it is the period during which we will begin to build a broader real-world understanding of how physicians and patients evaluate response and integrate mitapivat into long-term care. Taken together, these dynamics reinforce that AQVESME is delivering a healthy launch that is successfully progressing beyond the initial wave of adoption and into a broader expansion phase. As we move through H2 of the first launch year, our focus remains on expanding reach across the thalassemia community, expanding adoption in the non-transfusion-dependent segment while continuing to add new prescribers. We remain highly confident in the long-term opportunity for AQVESME and in our ability to build a durable, growing thalassemia franchise over time. Please move to the next slide.

Speaker #5: Taken together, these dynamics reinforce that ACVESMI is delivering a healthy launch that is successfully progressing beyond the initial wave of adoption and into a broader expansion phase.

Speaker #5: As we move through the second half of the first launch year, our focus remains on expanding reach across the thalassemia community—expanding adoption in the non–transfusion-dependent segments while continuing to add new prescribers.

Speaker #5: We remain highly confident in the long-term opportunity for ACVESMI and in our ability to build a durable, growing thalassemia franchise over time. Please move to the next slide.

Speaker #5: We are actively preparing for a potential sickle cell disease launch in the US, and are encouraged by both the commercial opportunity and the unmet need we see in this community.

Tsveta Milanova: We are actively preparing for a potential sickle cell disease launch in the US and are encouraged by both the commercial opportunity and the unmet need we see in this community. Our initial launch focus is on approximately 25,000 patients who are actively treated or in need of therapy today. We believe the population alone represents a meaningful opportunity for mitapivat, with potential to expand beyond the initial segment over time. Importantly, we are leveraging the capabilities, relationships, and insights we have developed through the thalassemia launch while continuing to invest in market access, education, and community engagement activities ahead of the PDUFA goal date. Pending FDA approval, we believe these efforts position us well to support a successful launch and to deliver mitapivat to patients in need of innovative treatment options. Please move to the next slide.

Speaker #5: Our initial launch focus is on approximately 25,000 patients who are actively treated or in need of therapy today. We believe that population alone represents a meaningful opportunity for me to pivot, with potential to expand beyond the initial segments over time.

Speaker #5: Importantly, we are leveraging the capabilities, relationships, and insights we have developed through the thalassemia launch, while continuing to invest in market access, education, and community engagement activities ahead of the PDUFA goal date.

Speaker #5: Spending FDA approval, we believe this effort positions us well to support a successful launch and to deliver me to pivot to patients in need of innovative treatment options.

Speaker #5: Please move to the next slide, and with that, I will hand the call over to Sarah to cover key R&D highlights from the Q4.

Tsveta Milanova: With that, I will hand the call over to Sarah to cover key R&D highlights from the quarter.

Speaker #1: Thank you, Sarah. Turning to our pipeline on the next slide, following recent portfolio prioritization decisions, we remain focused on advancing a diversified rare hematology portfolio with opportunities across multiple stages of development.

Sarah Gheuens: Thank you, Tsveta. Turning to our pipeline on the next slide. Following recent portfolio prioritization decisions, we remain focused on advancing a diversified rare hematology portfolio with opportunities across multiple stages of development. Mitapivat continues to anchor the portfolio with approved indications in pyruvate kinase deficiency and thalassemia, and a potential accelerated approval in sickle cell disease later this year. During H1 of this year, we achieved an important milestone with thalassemia approvals in Europe and the UAE, completing regulatory approvals across all four priority launch geographies following prior approvals in the US and KSA. Since Q1 results, we filed and received acceptance in the US for the mitapivat sNDA in sickle cell disease, with priority review and a PDUFA goal date of 1 November.

Speaker #1: Me to pivot continues to anchor the portfolio with approved indications in pyruvate kinase deficiency and thalassemia, and a potential accelerated approval in sickle cell disease later this year.

Speaker #1: During the first half of this year, we achieved an important milestone with thalassemia approvals in Europe and the UAE, completing regulatory approvals across all four priority launch geographies following prior approvals in the US and KSA.

Speaker #1: Since Q1 results, we filed and received acceptance in the US for the me to pivot SNDA in sickle cell disease, with priority review and a PDUFA goal date of November 1.

Speaker #1: We remain committed to bringing mitapivat to patients with sickle cell disease and recently dosed the first patient in RENEW, our Phase 3 confirmatory trial—an important milestone in advancing the program.

Sarah Gheuens: We remain committed to bringing mitapivat to patients with sickle cell disease and recently dosed the first patient in REIGNITE, our phase III confirmatory trial, an important milestone in advancing the program. We also strengthened the pipeline during the quarter through the in-licensing of cevidoplenib, a next generation Syk inhibitor that expands our reach within rare hematology and adds a compelling opportunity in immune thrombocytopenia. Beyond mitapivat and cevidoplenib, we continue to invest in future growth drivers, including AG-236 in polycythemia vera and AG-181 in phenylketonuria. Taken together, we believe the pipeline reflects a focused allocation of capital and resources towards programs where we see the greatest potential to create long-term value for patients and shareholders. Please move to the next slide.

Speaker #1: We also strengthened the pipeline during the Q4 through the in-licensing of Tevidoclinic, a next-generation sick inhibitor that expands our reach within rare hematology and adds a compelling opportunity in immune thrombocytopenia.

Speaker #1: Beyond me to pivot and Tevidoclinic, we continue to invest in future growth drivers, including AG236 in polycythemia vera and AG181 in phenylketonuria. Taken together, we believe the pipeline reflects a focused allocation of capital and resources toward programs where we see the greatest potential to create long-term value for patients and shareholders.

Speaker #1: Please move to the next slide. As we discussed when we announced the in-licensing of Tevidoclinic, our interest in the program is grounded in its potential to address some of the limitations that have historically constrained the SICK inhibitor class.

Sarah Gheuens: As we discussed when we announced the in-licensing of cevidoplenib, our interest in the program is grounded in its potential to address some of the limitations that have historically constrained the Syk inhibitor class. Cevidoplenib was designed to optimize both selectivity and pharmacokinetics, support a sustained target inhibition while maintaining a tolerability profile suitable for chronic use. The clinical data generated to date are encouraging and support this design rationale, demonstrating dose-dependent activity, no dose-limiting toxicities through phase II, and evidence of durable platelet responses. Taken together, these data support the rationale for advancing cevidoplenib as a next generation, highly selective Syk inhibitor. We're looking forward to engaging with the FDA in the coming months to align on progression to phase III. Next slide, please.

Speaker #1: Tevidoclinic was designed to optimize both selectivity and pharmacokinetics, supporting sustained target inhibition while maintaining a tolerability profile suitable for chronic use. The clinical data generated to date are encouraging and support this design rationale, demonstrating dose-dependent activity, no dose-limiting toxicities through phase two, and evidence of durable platelet responses.

Speaker #1: Taken together, these data support a rationale for advancing Tevidoclinic as a next-generation highly selective sick inhibitor. We're looking forward to engaging with the FDA in the coming months to align on progression to phase three.

Speaker #1: Next slide, please. At EHI in June, we were pleased to share a broad body of data across both thalassemia and sickle cell disease that continues to strengthen our confidence in mitapivat.

Sarah Gheuens: At EHA in June, we were pleased to share a broad body of data across both thalassemia and sickle cell disease that continues to strengthen our confidence in mitapivat. Across the portfolio, we have 10 abstracts accepted, including the RISE UP phase III study, which was selected for the EHA oral plenary session. In sickle cell disease, RISE UP demonstrated hemoglobin responses consistent with the mechanism of PK activation, with hemoglobin responders experiencing clinically meaningful improvement in sickle cell pain crisis-related endpoints and fatigue. At EHA, we presented new data showing clinically meaningful reductions in transfusion burden and red blood cell units transfused across the total trial population, exceeding historical experience with hydroxyurea. Importantly, outcomes from the subgroup of patients with at least one transfusion in the 52 weeks prior to enrollment directly informed the treatment effect and powering assumptions for the ongoing REIGNITE confirmatory trial, supporting accelerated approval.

Speaker #1: Across the portfolio, we have 10 aspects accepted, including the rise of phase three study, which was selected for the EHI oral plenary session. In sickle cell disease, rise of demonstrated hemoglobin responses consistent with the mechanism of PK activation, with hemoglobin responders experiencing clinically meaningful improvements in sickle cell pain crisis-related endpoints and fatigue.

Speaker #1: At EHI, we presented new data showing clinically meaningful reductions in transfusion burden and red blood cell units transfused across the total trial population, exceeding historical experience with hydroxyurea.

Speaker #1: Importantly, outcomes from the subgroup of patients with at least one transfusion in the 52-weeks prior to enrollment directly informed the treatment effect and firing of some transfer to ongoing reignite confirmatory trial, supporting accelerated approval.

Speaker #1: We also presented additional patient-reported outcomes data showing clinically meaningful improvements in how hemoglobin responders feel and function, including reductions in physical pain. In addition, 56-week follow-up data from the SATISFY Phase 2 investigator-sponsored trial in related membranopathies show robust hemoglobin response rates and mean hemoglobin improvements, as well as suggesting decreased iron burden.

Sarah Gheuens: We also presented additional patient-reported outcomes data showing clinically meaningful improvements in how hemoglobin responders feel and function, including reductions in physical pain. In addition, 56-week follow-up data from the SATISFY phase II investigator-sponsored trial in related membranopathies show robust hemoglobin response rates and mean hemoglobin improvement, as well as suggesting decreased iron burden. In non-transfusion-dependent thalassemia, we shared open-label extension data showing that 60% of patients continuing on mitapivat met criteria for hemoglobin response, and 60% of patients who switched onto mitapivat in the open-label extension achieved hemoglobin response. Additionally, subgroup analyses indicate high hemoglobin response rates for non-transfusion-dependent patients with high baseline hemoglobin levels, indicating that less severely anemic NTDT patients achieve improvements in hemoglobin levels and fatigue.

Speaker #1: In non-transfusion dependent thalassemia, we shared open label extension data showing that 60% of patients continuing on me to pivot met criteria for hemoglobin response and 60% of patients who switched onto me to pivot in the open label extension achieved hemoglobin response.

Speaker #1: Additionally, subgroup analyses indicate high hemoglobin response rates for non-transfusion dependent patients with high baseline hemoglobin levels, indicating that less severely anemic NPD patients achieved improvements in hemoglobin levels and fatigue.

Speaker #1: These data were received very favorably by the thalassemia community, and reinforced the value of mitapivat to pivot in non–transfusion-dependent patients, which comprise the majority of the diagnosed adult patients in the US.

Sarah Gheuens: These data were received very favorably by the thalassemia community and reinforce the value of mitapivat in non-transfusion-dependent patients, which comprise the majority of the eligible adult patients in the US. Taken together, these data reinforce the consistency of mitapivat's profile across indications and further strengthen our confidence in the long-term potential of mitapivat in hemolytic anemias. While we continue to advance and expand the mitapivat opportunity, we're also focused on building the next generation of potential growth drivers within rare hematology. AG-236 is an important example of that strategy. Next slide, please. Following encouraging phase I data, we're advancing AG-236 into an operationally seamless phase II-III development program in polycythemia vera. What continues to differentiate AG-236 is its potential profile with an evolving treatment landscape.

Speaker #1: Taken together, these data reinforce the consistency of me to pivot's profile across indications and further strengthen our confidence in the long-term potential of me to pivot in hemolytic anemia.

Speaker #1: While we continue to advance and expand the me to pivot opportunity, we're also focused on building the next-generation of potential growth drivers within rare hematology.

Speaker #1: AG236 is an important example of that strategy. Next slide, please. Following encouraging Phase 1 data, we're advancing AG236 into an operationally seamless Phase 2/3 development program in polycythemia vera.

Speaker #1: What continues to differentiate AG236 is its potential profile with an evolving treatment landscape. The molecule demonstrated hepcidin induction through day 57 and favorable effects on iron parameters in extended follow-up, supporting the potential for an every six-month dosing regimen without titration.

Sarah Gheuens: The molecule demonstrated hepcidin induction through day 57 and favorable effects on iron parameters in extended follow-up, supporting the potential for an every six-month dosing regimen without saturation. The phase II portion of the study is designed to identify the optimal therapeutic window across multiple dose levels while enabling efficient progression into the registrational portion of the program. More broadly, the seamless phase II-III strategy reflects our commitment to disciplined execution while advancing development as efficiently as possible, with phase II initiation planned for H2 2026. We believe AG-236 has the potential to further diversify our rare hematology leadership and contribute to our long-term growth beyond mitapivat. With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

Speaker #1: The phase two portion of the study is designed to identify the optimal therapeutic window across multiple dose levels while enabling efficient progression into the registrational portion of the program.

Speaker #1: More broadly, the seamless phase two, three strategy reflects our commitment to disciplined execution while advancing development as efficiently as possible, with phase two initiation planned for the second half of 2026.

Speaker #1: We believe AG236 has the potential to further diversify our rare hematology leadership and contribute to our long-term growth beyond me to pivot. With that, please move to the next slide, and I will hand the call back to Brian for closing remarks.

Speaker #2: Thank you, Sarah. Next slide, please. As we look across the business, we continue to make meaningful progress against the strategic priorities we established for 2026.

Brian Goff: Thank you, Sarah. Next slide, please. As we look across the business, we continue to make meaningful progress against the strategic priorities we established for 2026. We're building commercial momentum with AQVESME and thalassemia, reaching 442 cumulative prescriptions as of 30 June. We're advancing mitapivat toward a potential approval in sickle cell disease, which represents an important opportunity to expand our PK activation franchise and a potential next growth driver for the company. We're also advancing AG-236, our siRNA TMPRSS6 inhibitor for polycythemia vera, into an operationally seamless phase II-III program expected to begin in H2 this year. During the quarter, we further diversified our portfolio through the addition of cevidoplenib, a next-generation, highly selective Syk inhibitor in ITP progressing toward phase III. Importantly, our progress this year reflects both execution and discipline.

Speaker #2: We're building commercial momentum with ACT Vezni and thalassemia, reaching 442 cumulative prescriptions as of June 30th. We're advancing me to pivot toward a potential approval in sickle cell disease, which represents an important opportunity to expand our PK activation franchise and a potential next growth driver for the company.

Speaker #2: We're also advancing AG236, our siRNA 10.6 inhibitor for polycythemia vera, into an operationally seamless phase two, three program, expected to begin in the second half of this year.

Speaker #2: And during the quarter, we further diversified our portfolio through the addition of sevadoplinib, a next-generation highly selective sick inhibitor in ITP progressing toward phase three.

Speaker #2: Importantly, our progress this year reflects both execution and discipline. We're investing behind the opportunities where we believe Agios can have the greatest impact for patients and create the strongest long-term value for shareholders.

Brian Goff: We're investing behind the opportunities where we believe Agios can have the greatest impact for patients and create the strongest long-term value for shareholders. Next slide. Taken together, we enter H2 the year with a growing commercial foundation, a meaningful near-term regulatory catalyst, and an increasingly diversified pipeline and the financial strength to execute on our strategy. Next slide, please. Today, Agios is anchored by a growing commercial business and supported by a pipeline spanning multiple development stages and disease areas. Across the portfolio, we are pursuing opportunities where differentiated biology, meaningful patient unmet need, and disciplined execution can support durable long-term growth. Collectively, these opportunities represent rare disease markets estimated at more than $10 billion in 2030.

Speaker #2: Next slide. Taken together, we enter the second half of the year with a growing commercial foundation, a meaningful near-term regulatory catalyst, an increasingly diversified pipeline, and the financial strength to execute on our strategy.

Speaker #2: Next slide, please. Today, AGIOS is anchored by a growing commercial business and supported by a pipeline spanning multiple development stages and disease areas. Across the portfolio, we are pursuing opportunities where differentiated biology meaningful patient unmet need and disciplined execution can support durable long-term growth.

Speaker #2: Collectively, these opportunities represent rare disease markets, estimated at more than $10 billion in 2030. Before we open the call for questions, I'd like to thank the entire AGIOS team for their unwavering commitment to patients and their continued dedication to executing on our strategy.

Brian Goff: Before we open the call for questions, I'd like to thank the entire Agios team for their unwavering commitment to patients and their continued dedication to executing on our strategy. Their passion, resilience, and focus have been instrumental in the progress we've made this year. With that, thank you all for joining us today. Operator, we're ready to begin the question and answer session.

Speaker #2: Their passion, resilience, and focus have been instrumental in the progress we've made this year. And with that, thank you all for joining us today.

Speaker #2: Operator, we're ready to begin the question-and-answer session.

Speaker #3: Thank you. Ladies and gentlemen, to ask a question, please press star 11 on your telephone. Then wait for your name to be announced. To withdraw your question, please press star 11 again.

Operator: Thank you. Ladies and gentlemen, to ask a question, please press star 11 on your telephone, wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Alec Stranahan with Bank of America. Your line is open.

Speaker #3: Please stand by while we compile the Q&A roster. Our first question comes from the line of Alex Stranahan with Bank of America. Your line is open.

Alec Stranahan: Hey, guys. Thanks for taking my questions. Congrats on the really strong quarter here. Two questions from me. First, on time on treatment in the commercial setting, do you think the ENERGIZE studies are a good barometer here? Just trying to think about how the dynamic of patients potentially coming off their PK could play into H2 sales. When you look at the time on treatment, did this change at all between Q1 to Q2? Did it move closer or further away from that 10 to 12-week average range that you're setting out? Are you starting to see any repeat prescriptions under the REMS program at this point? Thank you.

Speaker #4: Hey, guys. Thanks for taking my questions and congrats on the really strong quarter here. Two questions from me. First, on time on treatment in the commercial setting, do you think the energized studies are a good barometer here?

Speaker #4: Just trying to think about how the dynamic of patients potentially coming off their PE could play into second-half sales. And then when you look at the time on treatment, did this change at all between one Q to two Q?

Speaker #4: Did it move closer to or further away from that 10- to 12-week average range that you're setting out? And I guess, are you starting to see any repeat prescriptions under the REMS program at this point?

Speaker #4: Thank you.

Speaker #2: Thanks, Alex. So two-parter. So Sarah, you can take the first one. Actually, you'll take both of these. So in the time on treatment and energized as an analog.

Brian Goff: Thanks, Alex. Two-parter. Tsveta, you can take the first one. Actually, you'll take both of these.

Tsveta Milanova: Yeah.

Brian Goff: On the time on treatment and ENERGIZE as an analog. The second one, I think, Alex, you're asking about not time on treatment, but time to treatment, from the demand to initiation. Tsveta, you want to take that?

Speaker #2: And then the second one, I think, Alex, you're asking about not time on treatment, but time to treatment from the demand to initiation. So, Sarah, you want to take that?

Tsveta Milanova: Absolutely. We are very pleased with the strong initial start of the AQVESME launch, Alec. As we mentioned, we have in total 442 prescriptions from REMS-certified physicians for the first two quarters of the launch. As we look ahead, in the first couple of quarters, we benefited from faster than anticipated time to treatment initiation. It was faster than the 10 to 12 weeks, given that we have prescriptions coming from highly motivated patients and physicians. Keeping that in mind, we will start to reach the natural point of the six months, at which physicians and patients are going to evaluate benefits for the product and continuation rates. That's going to be more in the H2, and we'll monitor that closely. Currently, what we see from the market is a very strong feedback and a positive feedback from the community.

Speaker #1: Absolutely. We are very pleased with the strong initial start of the ACT Vezni launch, Alex, and as we mentioned, we have, in total, 442 prescriptions from REMS-certified physicians for the first two quarters of the launch.

Speaker #1: As we look ahead, in the first couple of quarters, we benefited from a faster-than-anticipated time to treatment initiation. So it was faster than the 10- to 12-week timeframe.

Speaker #1: Given that we had prescriptions coming from highly motivated patients and physicians, keeping that in mind, we'll start kind of the natural to reach the natural point of the six months at which physicians and patients are going to evaluate benefit for the product and continuations rate.

Speaker #1: But that's going to be more in the second half of the year, and we'll monitor that closely. Currently, what we see from the market is very strong feedback and positive feedback from the community.

Speaker #1: So we expect continuation rates to be in line with the energized study. And we'll continue to monitor that. But the product performance is very strong in the market.

Tsveta Milanova: We expect continuation rates to be in line with the ENERGIZE study. We'll continue to monitor that, but the product performance is very strong in the market. When it comes to time to treatment initiation, we start seeing that as we penetrate into the NTDT settings to move closer and closer to what we initially expected, the 10 to 12-week range. As we move into the H2, we will continue to monitor that, but we expect to be well within the 10 to 12 weeks, given the strong penetration in the NTDT settings. Your third question was around repeat prescriptions for the REMS. When we look at that, of course, we have patients who have been on therapy for multiple months. We do start seeing the repeat prescriptions and patients and physicians are going through the REMS process very smoothly.

Speaker #1: When it comes to time to treatment initiation, we start seeing that as we penetrate into the entity setting to move closer and closer to what we initially expected, the 10 to 12-week range.

Speaker #1: And as we move into the second half of the year, we will continue to monitor that, but we expect to be well within the 10 to 12-week, given the strong penetration in the entity setting.

Speaker #1: And your third question was around repeat prescriptions. For the REMS, when we look at that, of course, we have patients who have been on therapy for multiple months.

Speaker #1: So we do start seeing the repeat prescriptions, and patients and physicians are going through the REMS process very, very smoothly.

Alec Stranahan: Good. Thank you.

Speaker #4: Thank you.

Speaker #3: Thank you. Our next question comes from the line of Andrew Barrons with LeaveRank. Your line is open.

Operator: Thank you. Our next question comes from the line of Andrew Barrons with Leerink. Your line is open.

Andrew Barrons: Hi. Thanks, and congrats on the strong execution. I guess I just want to expand a little bit on the persistence rate, since it is so important going forward. Is there anything that you can tell us about maybe the expanded access program at all? Just what the experience will be like for these patients in the real world. The other thing that is obviously very important is going to be a sickle cell label, whether it is on AQVESME or PYRUKYND. What factors will go into that? Is there anything you can tell us in these early days ahead of the 1 November PDUFA date to give us confidence that you will not have a REMS or have to potentially reduce the pricing for AQVESME in thalassemia? Thanks.

Andrew Berens: Hi. Thanks, and congrats on the strong execution. I guess I just want to expand a little bit on the persistence rate, since it is so important going forward. Is there anything that you can tell us about maybe the expanded access program at all? Just what the experience will be like for these patients in the real world. The other thing that is obviously very important is going to be a sickle cell label, whether it is on AQVESME or PYRUKYND. What factors will go into that? Is there anything you can tell us in these early days ahead of the 1 November PDUFA date to give us confidence that you will not have a REMS or have to potentially reduce the pricing for AQVESME in thalassemia? Thanks.

Speaker #5: Hi. Thanks. And congrats on the strong execution I guess I just want to expand a little bit on the persistence rate, since it's so important going forward.

Speaker #5: Is there anything that you can tell us about maybe the expanded access program at all? What the experience will be like for these patients in the real world?

Speaker #5: And then the other thing that's obviously very important is going to be a sickle cell label. Whether it's on a CASNI or PyruKind, what factors will go into that?

Speaker #5: And is there anything you can tell us in these early days ahead of the November 1st PDUPA that has been as confident that you won't have a REMS or have to potentially reduce the pricing for a CASNI and thalassemia?

Speaker #5: Thanks.

Speaker #2: Thanks, Andy. And I will just say again, thanks for the comments about the strong quarter. I am really pleased and proud of the continued execution from Tsveta and the team.

Brian Goff: Thanks, Andy. I will just say again, thanks for the comments about the strong quarter. I am really pleased and proud with the continued execution from Tsveta and the team. I think on the persistency, Andy, maybe we will start with Sarah just reflecting on the clinical trial, the open label extensions, and what we saw. It still is early days for us to quantify persistence, but we always look at the trials and OLEs as a proxy.

Speaker #2: I think on the persistency, Andy, maybe we'll start with Sarah just reflecting on the clinical trial, the open label extensions, and what we saw because it still is early days for us to quantify persistence, but we always look at the trials and OLEs as a proxy.

Speaker #1: Yes. Thanks, Brian. And I think Andy here, we can really look at the open label data that we presented at EHA recently as well.

Tsveta Milanova: Yes. Thanks, Brian. I think, Andy, here we can really look at the open label data that we presented at EHA recently as well. As you know, we have very high continuation rates for people who finish the clinical trials and then go into the open label extension. Now we have the benefit of being able to have followed them for a period of time post randomized control trial, where you see there is a good maintenance of response. Patients do continue on the drug. You see that maintenance of hemoglobin, the maintenance of anti-hemolytic response, and people feeling good.

Sarah Gheuens: Yes. Thanks, Brian. I think, Andy, here we can really look at the open label data that we presented at EHA recently as well. As you know, we have very high continuation rates for people who finish the clinical trials and then go into the open label extension. Now we have the benefit of being able to have followed them for a period of time post randomized control trial, where you see there is a good maintenance of response. Patients do continue on the drug. You see that maintenance of hemoglobin, the maintenance of anti-hemolytic response, and people feeling good.

Speaker #1: So, as you know, we have very high continuation rates for people who finish the clinical trials and then go into the open-label extension.

Speaker #1: And now we have the benefit of being able to have followed them for a period of time post–randomized controlled trial, where you see there is a good maintenance of response.

Speaker #1: So patients do continue on the drug. And you see that maintenance of hemoglobin, the maintenance of anti-hemolytic response in people feeling good. Another point there, what was exciting to see at the EHA dataset was that people with a higher hemoglobin also had good response to the treatment, which is important, of course, as we continue to expand the patients we capture in the launch for them.

Tsveta Milanova: Another point there, what was exciting to see at the EHA dataset was that people with higher hemoglobin also had good response to the treatment, which is important, of course, as we continue to expand the patients we capture in the launch for the non-transfusion-dependent patients.

Sarah Gheuens: Another point there, what was exciting to see at the EHA dataset was that people with higher hemoglobin also had good response to the treatment, which is important, of course, as we continue to expand the patients we capture in the launch for the non-transfusion-dependent patients.

Speaker #1: And non-transfusion-dependent patients. And so yes, so I think the clinical trial data is actually the best way to look at that question right now.

Sarah Gheuens: Yes, I think the clinical trial data is actually the best way to look at that question right now. Yeah.

Speaker #1: And yeah.

Tsveta Milanova: Yeah. I just wanted to add that I've been spending a lot of time with clinicians in the field, had the opportunity to hear their feedback on the EHA data. As we enter into the H2 of the year, and we start experiencing the real-world evaluation of persistency, I'm very confident that we'll see the repetition of what we see in the clinical trials in terms of continuation rates for six months.

Speaker #3: Yep. And I just wanted to add that I've been spending a lot of time with clinicians in the field, had the opportunity to hear their feedback on the EHA data.

Speaker #3: And as we enter into the second half of the year, and we start experiencing kind of the real-world evaluation of persistency, I'm very confident that we'll see the repetition of what we see in the clinical trials in terms of continuation rates post six months.

Speaker #6: And then in regards to.

Sarah Gheuens: And then in regards to-

Andrew Barrons: Can you give us-

Andrew Berens: Can you give us-

Speaker #5: Can you give us. I'm just going to ask, can you give us a can you give us a number, a percentage that you saw in the open label extension study of patients that stayed on?

Sarah Gheuens: Oh, sorry.

Sarah Gheuens: I was just going to ask, can you give us a number, a percentage that you saw in the open label extension study of patients who stayed on?

Andrew Berens: I was just going to ask, can you give us a number, a percentage that you saw in the open label extension study of patients who stayed on?

Sarah Gheuens: For ENERGIZE, we had an over 90% continuation from the clinical trial. In regards. Yeah, and then, of course, as time continues, clinical trials are burdensome. It drops a little, but it's very good persistence, both for PKD, for thalassemia, for sickle cell disease in the clinical trial. What was interesting there is also the response rate with longer exposure, which it's important for thalassemia from in the early 40%, we had some non-responders convert into responders. We got to a 60% response rate there. The clinical trial data is very good.

Speaker #6: So, for ENERGIZE, we had over 90% continuation from the clinical trial. In regards—yeah, and then, of course, as time continues, clinical trials are burned, so it drops a little, but it's very, very good persistence, both for PKD, for thalassemia, and for sickle cell disease in the clinical trials.

Speaker #6: What was interesting there is also the response rate with longer exposure. It's important for thalassemia— from in the early 40%, we had some non-responders convert into responders.

Speaker #6: So we got to a 60% response rate there. So the clinical trial data is very good.

Speaker #2: And we know, obviously, that's an important metric for us going forward. And but we're still early days. This is our second full quarter of launch, which in a way matches the period of time for the energized trial.

Brian Goff: We know obviously that's an important metric for us going forward. We're still early days. This is our second full quarter of launch, which in a way matches the period of time for the ENERGIZE trial. We'll continue to monitor and of course, implement appropriate patient services support to help patients continue on therapy. Andy, maybe you can just repeat the second part of your question.

Speaker #2: So, we'll continue to monitor, and of course, implement appropriate patient services support to help patients continue on therapy. Andy, maybe you can just repeat the second part of your question.

Speaker #5: Yeah. Just, I mean, obviously, I don't think anyone expects sickle cell pricing to be as resilient as thalassemia or PKD. So it really depends on whether you get sickle cell added to CASNI or PyroKind.

Andrew Barrons: Yeah. Obviously, I don't think anyone expects sickle cell pricing to be as resilient as thalassemia or PKD. It really depends on whether you get sickle cell added to AQVESME or PYRUKYND. What do you think is going to drive that decision and any insights now that we're several months away from the PDUFA about which brand sickle cell may be added to if approved?

Andrew Berens: Yeah. Obviously, I don't think anyone expects sickle cell pricing to be as resilient as thalassemia or PKD. It really depends on whether you get sickle cell added to AQVESME or PYRUKYND. What do you think is going to drive that decision and any insights now that we're several months away from the PDUFA about which brand sickle cell may be added to if approved?

Speaker #5: What do you think is going to drive that decision? And any insights now that we're several months away from the PDUPA about which brand sickle cell may be added to, if approved?

Speaker #1: Yeah, so the PDUFA is indeed November 1st, priority review, so we're very excited about that. We have not further discussed which brand name is going to be used.

Sarah Gheuens: Yeah. The PDUFA is indeed 1 November priority review, we're very excited about that. We have not further discussed which brand name is going to be used, as you know, the clinical trial data looked very good. We did not have the hepatocellular injury observed in the sickle cell disease patients, therefore it may not warrant a REMS. Either way, our teams are ready to execute a launch with or without a REMS, more to come.

Speaker #1: But as you know, the clinical trial data looked very good. We did not have the hepatocellular injury observed in the sickle cell disease patients.

Speaker #1: So, therefore, it may not warrant a REMS. Either way, our teams are ready to execute a launch with or without a REMS. So, more to come.

Speaker #3: Absolutely. And as always, we’ll provide more specifics at the time of launch once we have the label. We’ll price the product for that indication and across the portfolio to maximize the opportunity based on the clinical data and, of course, the market environment at the time.

Tsveta Milanova: Absolutely. As always, we'll provide more specifics at the time of launch once we have the label. We'll price the product for that indication and across the portfolio to maximize the opportunity based on the clinical data and of course, the market environment at the time. I must say, we are in a very strong position given that it's our third indication. There is a very high unmet need in sickle cell disease. We do have a very strong market access team. I'm very proud of the progress they made in thalassemia with the payer policies, and we'll continue to learn and build from here.

Speaker #3: I must say we are in a very strong position given that it's our third indication. There is a very high unmet need in sickle cell disease.

Speaker #3: And we do have a very strong market access team. I'm very proud of the progress they've made in thalassemia with the payer policies and will continue to learn and build from here.

Speaker #5: Okay. Well, thanks for answering the questions, and congrats again on the strong quarter. It looks like it's going to continue.

Andrew Barrons: Right. Well, thanks for answering the questions and congrats again on the strong quarter. It looks like it's going to continue.

Andrew Berens: Right. Well, thanks for answering the questions and congrats again on the strong quarter. It looks like it's going to continue.

Speaker #2: Thanks, Andy.

Brian Goff: Thanks, Andy.

Brian Goff: Thanks, Andrew.

Speaker #3: Please stand by for our next question. Our next question comes from the line of Gregory Renza, with Truist Securities. Your line is open.

Operator: Please stand by for our next question. Our next question comes from the line of Gregory Renza with Truist Securities. Your line is open.

Supat Ontongkram: Hi, team. This is Supat Ontongkram. Congrats. Let me add the congrats to the team, too, on an excellent quarter. My question is two parts as well, if I may. As we enter the H2 2026, and we move beyond the initial wave of highly motivated transfusion-dependent patients, how should we think about the run rate of new patient starts, particularly in the broader non-transfusion-dependent population? The second part is, where are you at in terms of gross? I know it's variable this quarter. Where are you at within the range of the 10% to 20% expected target? Now you're at 75% of cover life. Thanks and congrats again.

Supawat Thongthip: Hi, team. This is Supat Ontongkram. Congrats. Let me add the congrats to the team, too, on an excellent quarter. My question is two parts as well, if I may. As we enter the H2 2026, and we move beyond the initial wave of highly motivated transfusion-dependent patients, how should we think about the run rate of new patient starts, particularly in the broader non-transfusion-dependent population? The second part is, where are you at in terms of gross? I know it's variable this quarter. Where are you at within the range of the 10% to 20% expected target? Now you're at 75% of cover life. Thanks and congrats again.

Speaker #4: Hi, team. This is support on for Greg. Congrats at the congrats to the team too on an excellent quarter. So my question is two parts as well if I may.

Speaker #4: So as we enter the second half of 2026 and we move beyond the initial wave of highly motivated transfusion-dependent patients, how should we think about the run rate of new patient starts?

Speaker #4: Particularly in the broader non-transfusion-dependent population. And the second part is, where are you at in terms of growth? I know it's favorable this quarter.

Speaker #4: Where are you at within the range of the 10 to 20 percent expected target? Now you are at 75% of cover life. Thanks and congrats again.

Speaker #2: Thanks, Supat. So Sveta, maybe you can start with. And I think you said it the right way as we extend further into the broader reach and the NTD population study.

Brian Goff: Thanks, Supat. Tsveta, maybe you can start with, and I think you said it the right way, as we extend further into the broader reach in the NTD population. Tsveta, you want to take that, and then we'll do gross to net separately?

Speaker #2: You want to take that, and then we'll do gross-to-net separately.

Speaker #3: Absolutely. I'm very pleased with the progress so far. We are really seeing a very healthy start to the launch, both from penetration into the community setting, where the majority of prescribers are, as well as penetration in the entity setting, which is the bigger commercial opportunity.

Tsveta Milanova: Absolutely. I'm very pleased with the progress so far. We are really seeing a very healthy start of the launch, both from penetration into the community setting where the majority of prescribers are, as well as the penetration in the NTD setting, which is the bigger commercial opportunity. As we mentioned in Q2, we added 200 prescriptions from REMS-certified physicians. As we move into H2 of the year, prescriptions growth and revenue growth are not going to be directly correlated on a perfect basis, given that we're moving into the more mature phase of the launch. The revenues really also depend on time to treatment initiations, REMS onboarding, and persistency as we've discussed.

Speaker #3: As we mentioned in the second quarter, we added 200 prescriptions from REMS-certified physicians. As we're moving to the second half of the year, prescriptions growth and revenue growth are not going to be directly correlated on a perfect basis given that we're moving into the more mature phase of the launch.

Speaker #3: And revenues really also depend on time-to-treatment initiations. REMS onboarding and persistency as we've discussed. Moving ahead, as we're moving to the entity setting, we expect the time-to-treatment initiation to move well into the 10 to 12 weeks.

Tsveta Milanova: Moving ahead, as we move into the NTD setting, we expect the time to treatment initiation to move well into the 10 to 12 weeks. Given the fact that these patients have less frequent visits to the healthcare professionals, and they'll need to go through the insurance verification as well as the REMS process as well. We are really encouraged by the rate of patient adoption, the progress that we are making, the way the patients are converting and staying on therapy at this part of the launch, and most importantly, the really positive feedback from what I'm hearing from the clinicians on the product profile in the real world.

Speaker #3: Given the fact that these patients have less frequent visits to the healthcare professionals, and they'll need to go through the insurance verifications as well as the we are really, really encouraged by the rate of patient adoptions, the progress that we are making, the way the patients are converting, and staying on therapy at this part of the launch.

Speaker #3: And most importantly, the really positive feedback from what I'm hearing from the clinicians on the product profile in the real world.

Speaker #2: Great. And then Supat, I think the second part of your question was around the 10 to 20 percent guidance that we've given on gross-to-nets.

Brian Goff: Great. Then, Supat, I think the second part of your question was around the 10% to 20% guidance that we've given on gross to net. Cecilia, do you want to comment here?

Speaker #2: Cecilia, do you want to comment here?

Speaker #3: Yeah. So we expect that to continue to be in that range of 10 to 20 percent as we guided before. There's always some quarter-over-quarter variability, but on aggregate, that's a range we still expect to see.

Cecilia Jones: Yeah. We expect that to continue to be in that range of 10% to 20% as we guided before. There's always some quarter-over-quarter variability, but on aggregate, that's a range we still expect to see.

Speaker #3: Thank you. Please stand by for our next question. Our next question comes from the line of Mark Frim with TD Cohen. Your line is open.

Operator: Thank you. Please stand by for our next question. Our next question comes from the line of Marc Frahm with TD Cowen. Your line is open.

Speaker #5: Hi. Thanks for taking my questions. And completely get the kind of pushes and pulls on turning a TRX into actual revenue and, of course, there will be some drop-off of patients on kind of the back end starting in the second half.

Marc Frahm: Hi, thanks for taking my questions. Completely get the pushes and pulls on turning a TRx into actual revenue, of course, there will be some drop-off of patients on the back end starting in H2. Do you view that 200 patients at the top of the funnel as now a sustainable rate, or does that still reflect a little bit of that bolus that you talked about for Q1 of the backlog of REMS certifications and the highly motivated patients?

Speaker #5: But do you view that kind of 200 patients at the top of the funnel as now kind of a sustainable rate, or does that still reflect a little bit of that bolus that you kind of talked about for Q1 of the backlog of REMS certifications and kind of the highly, highly motivated patients?

Speaker #2: Yeah. Maybe I'll start, and I'm going to turn it over to Sveta. I think, Mark, a good way to think about a comment we've made several times in terms of engaged patients, engaged clinicians, is that's a gradient.

Brian Goff: Yeah. Maybe I'll start, then I'm going to turn it over to Tsveta. I think, Marc, a good way to think about a comment we've made several times in terms of engaged patients, engaged clinicians, is that's a gradient. We know that we're still on the front end of that gradient. Tsveta just commented on it, too, as we move further into the NTD population, by definition, these patients tend to have less frequency of clinical interactions. That's essentially the dynamic that we're up against. Tsveta, what would you add?

Speaker #2: And we know that we're still on the front end of that gradient. As we, instead of just commenting on it too, as we move further into the NTD population, by definition, these patients tend to have less frequency of clinical interactions.

Speaker #2: And so that's essentially the dynamic that we're up against. Sveta, what would you add?

Tsveta Milanova: Yeah. No, absolutely. As I also mentioned in my prepared remarks, looking into entering a new phase of the launch in Q2, we expect prescription growth and the revenue growth not to correlate directly in every single quarter due to the timed treatment initiations, the patient conversion rate, persistency, and inter-quarter ordering variability. That's why we'll actually move away from this initial indicator of demand after Q3, which is prescriptions, to something that we believe is more reflective of the underlying health of the business, which is going to be revenue. When you think about how H1 is going to transition into the next phase of the launch, which is H2.

Speaker #3: Yeah, no, absolutely. And as I also mentioned in my prepared remarks, looking into entering a new phase of the launch in the second quarter, we expect prescription growth and revenue growth not to correlate directly in every single quarter due to the time to treatment initiations.

Speaker #3: The patient conversion rates, persistency, and kind of interquarter ordering variability—that's why we'll actually move away from this initial indicator of demand after the third quarter, which is prescriptions, to something that we believe is more reflective of the underlying health of the business, which is going to be revenue.

Speaker #3: When you think about how the first half is going to transition into the next phase of the launch, which is the second half, in the first half, in Q1 and partially in Q2, we really benefited from this early adopters, highly motivated patients and physicians, the delay in the PDUFA, which created an anticipation of the launch.

Tsveta Milanova: In H1, in Q1, and partially in Q2, we really benefited from these early adopter, highly motivated patients and physicians, the delay in the PDUFA, which created the anticipation for the launch, and patients and physicians who are ready to start as quickly as possible. As we move into the second part of the launch, what I'm looking for is really the underlying dynamics of the launch, which allow us to further penetrate into the community setting, a very strong adoption into the NTDT setting across alpha and beta thalassemia patients, and moving into that more steady state of 10 to 12-week treatment initiation. We are very encouraged of the way the launch is going and the way the team is executing.

Speaker #3: In the for the launch and patients and physicians who were ready to start as quickly as possible. As we move into the second part of the launch, what I'm looking for is really the underlying dynamics of the launch, which allow us to further penetrate into the community setting, a very strong adoption into the entity setting across Alpine Bay to Thalassemia patients, and moving into that more steady state of 10 to 12 weeks treatment initiation.

Speaker #3: So we are very encouraged of the way the launch is going. And the way the team is executing.

Speaker #5: Okay. That's all helpful. And then maybe just on the other end of the funnel, I'm just continuation rate. Do you view these initial kind of very highly motivated patients and clinicians that are using that were starting therapy and Q1 and early Q2, are those patients, do you think, more likely to stay on drug because of that motivation, or are they perhaps the very hard-to-treat patients and maybe they'll have a somewhat higher discontinuation rate than kind of the long-term number might end up being?

Marc Frahm: Okay. That's all helpful. Then maybe just on the other end of the funnel on the discontinuation rate, do you view these initial very highly motivated patients and clinicians that were starting therapy in Q1 and early Q2, are those patients, do you think, more likely to stay on drug because of that motivation? Are they perhaps the very hard-to-treat patients and maybe they'll have a somewhat higher discontinuation rate than the long-term number might end up being?

Tsveta Milanova: As we progress into the next phase of the launch, we'll provide more color on to what we see in the real world. My suggestion for now and what we're hearing from the clinicians is that the core period in the clinical trials is a very good proxy for continuation, and we'll continue to learn more. I'm very pleased with the payer policies that have been issued. They really allow a lot of flexibility for patients and physicians to make informed treatment choices on continuation. The policies are really for managing patients to clinical trial criteria or better. Let's use for now the clinical trial as a proxy.

Speaker #3: As we progress into the next phase of the launch, we'll provide more color on what we see in the real world. My suggestion for now, and what we're hearing from the clinicians, is that the core period in the clinical trials is a very good proxy for continuation.

Speaker #3: And we'll continue to learn more I'm very pleased with the payer policies that have been issued they really allow a lot of flexibility for patients and physicians to make informed treatment choices on continuation.

Speaker #3: The policies are really managing for managing patients to clinical trial criteria or better. So let's use for now the clinical trial as a proxy.

Speaker #5: Okay. Thanks.

Marc Frahm: Okay. Thanks.

Speaker #2: Thanks, Mark.

Brian Goff: Thanks, Marc.

Speaker #3: Thank you. Our next question comes from the line of Samantha Simmoncal with Citi. Your line is open.

Operator: Thank you. Our next question comes from the line of Samantha Simko with Citi. Your line is open.

Operator: Thank you. Our next question comes from the line of Samantha Semenkow with Citi. Your line is open.

Speaker #6: Hi, good morning. Thanks very much for taking the question, and let me add my congratulations on the strong quarter. I'm wondering if you could just speak a little bit more to the dynamics of the clinical evaluation after six months of treatment that you were speaking about in your prepared remarks.

Samantha Simko: Hi. Good morning. Thanks very much for taking the question, Amiya, my congrats on the strong quarter. I'm wondering if you could just speak a little bit more to the dynamics of the clinical evaluation after six months of treatment that you were speaking on in your prepared remarks. What are physicians viewing as acceptable clinical bar for continuing treatment? Is this six months clinical mark, is that pretty strict, or is there some flexibility where it could vary when a physician would be looking to assess the clinical progress for a patient? I have a follow-up.

Samantha Semenkow: Hi. Good morning. Thanks very much for taking the question, Amiya, my congrats on the strong quarter. I'm wondering if you could just speak a little bit more to the dynamics of the clinical evaluation after six months of treatment that you were speaking on in your prepared remarks. What are physicians viewing as acceptable clinical bar for continuing treatment? Is this six months clinical mark, is that pretty strict, or is there some flexibility where it could vary when a physician would be looking to assess the clinical progress for a patient? I have a follow-up.

Speaker #6: What are physicians viewing as acceptable clinical bar for continuing treatment? And is this six-month clinical mark, is that pretty strict, or is there some flexibility where it could vary when a physician would be looking to assess the clinical progress for a patient?

Speaker #6: And I have a follow-up.

Speaker #2: Thanks, Sim. And this is another good one for Sveta. Also, we have important learnings from our experience already with PKD—now over many years—in terms of evaluation.

Brian Goff: Thanks, Sam. This is another good one for Tsveta. Also where we have important learnings from our experience already with PKD now over many years in terms of evaluation.

Speaker #3: Absolutely. So there is a variability of how patients and physicians define benefit. And I'm going to use the word benefit because it's quite often goes beyond what is defined as the primary endpoint in the clinical trials.

Tsveta Milanova: Absolutely. There is a variability of how patients and physicians define benefit. I am going to use the word benefit because it quite often goes beyond what is defined as the primary endpoint in the clinical trials. Of course, for transfusion-dependent patients, both patients and physicians will look at transfusion reductions both in terms of ability to expand the time between transfusions, as well as reducing the amount of transfused blood, and both of these aspects are important. What we hear from physicians, and I had the opportunity to meet both with patients and physicians recently at the Thalassemia Foundation meeting, is they really do that on a patient-by-patient basis. Majority of them mentioned the six months, both driven by the fact that our clinical trials were within that timeframe, but it is also a natural opportunity for them to evaluate initial benefits. They will make decisions based on that.

Speaker #3: Of course, for transfusion-dependent patients, both patients and physicians will look at transfusion reductions, both in terms of ability to expand the time between transfusions as well as reducing the amount of transfused blood.

Speaker #3: And both of these aspects are important. What we hear from physicians—and I had the opportunity to meet both with patients and physicians, as recently as at the Culis Anemia Foundation meeting—is that they really do that on a patient-by-patient basis. The majority of them mentioned the six months, both driven by the fact that our clinical trials were within that time frame, but it's also a natural opportunity for them to evaluate initial benefit.

Speaker #3: And they'll make decisions based on that. Transfusion reduction in the TDT patients will be important. They are not necessarily going to stick to what was defined as a 50% reduction in the clinical study.

Tsveta Milanova: Transfusion reduction in the TDT patients will be important. They are not necessarily going to stick to what was defined as a 50% reduction in the clinical study. It is going to be on an individual patient basis, and if they want to continue on therapy as well and how they feel between the transfusions is also important. On the NTDT setting, they are going to look on improvement in hemoglobin. The 1 gram per deciliter is not like a hard yes or no. They will also look at the improvement in hemolytic parameters, very importantly in the NTDT setting is how patients feel. The reduction in fatigue is a key driver both for patients and physicians to continue on therapy irrespective of the actual level of hemoglobin improvement.

Speaker #3: It's going to be on an individual patient basis. And if they want to continue on therapy as well and how they feel between the transfusions is also important.

Speaker #3: On the endpoint setting, they're going to look for improvement in hemoglobin. The one gram per deciliter is not like a hard yes or no.

Speaker #3: They'll also look at the improvement in hemolytic parameters. And very importantly, in the entity setting is how patients feel. The reduction in fatigue is a key driver both for patients and physicians to continue on therapy irrespective of the actual level of hemoglobin improvement.

Speaker #3: So we are very encouraged by what we hear from our customers and look forward to learning more in the second half of the year.

Tsveta Milanova: We are very encouraged from what we hear from our customers and look forward to learning more in H2 of the year.

Samantha Simko: Great. Thanks very much. Just a second question about the evolution of the prescriber base. Are you seeing physicians write scripts for multiple patients that they manage? I am wondering if there is any sort of dynamic that you could share that you have seen over the first two quarters of launch. Thanks very much.

Samantha Semenkow: Great. Thanks very much. Just a second question about the evolution of the prescriber base. Are you seeing physicians write scripts for multiple patients that they manage? I am wondering if there is any sort of dynamic that you could share that you have seen over the first two quarters of launch. Thanks very much.

Speaker #6: Great. Thanks very much. And then just a second question about the evolution of the prescriber base. Are you seeing physicians write scripts for multiple patients that they manage?

Speaker #6: I'm wondering if there's any sort of, I guess, dynamic that you could share that you've seen over the first two quarters of launch. Thanks very much.

Speaker #3: Absolutely. When I look at our prescriber base, the most important thing for me is to look for breadth of prescribing because thalassemia majority of the patients are managed in the community.

Tsveta Milanova: Absolutely. When I look at our prescriber base, the most important thing for me is to look for breadth of prescribing because thalassemia, majority of the patients are managed in the community, and we don't have that much breadth across the therapy area. I see a very, very strong breadth of prescribing across the country from different clinicians. I'm very pleased with the healthy start of the launch. We do have a small number of key opinion leaders who have written for more than one patient, and we continue to see prescriptions coming from these prescribers. We expect that to continue. They do have a stable patient base. Really our opportunity is to continue to penetrate the community setting.

Speaker #3: And we don't have that much breadth across the therapy area. And I see a very, very strong breadth of prescribing across the country, from different clinicians.

Speaker #3: So I'm very pleased with the healthy start of the launch. We do have a small number of key opinion leaders who have written for more than one patient.

Speaker #3: And we continue to see prescriptions coming from these prescribers, and we expect that to continue, as they do have a stable patient base. But really, our opportunity is to continue to penetrate the community setting.

Speaker #6: Thanks very much.

Samantha Simko: Thanks very much.

Samantha Semenkow: Thanks very much.

Speaker #2: Thank you.

Brian Goff: Thank you.

Speaker #3: Please stand by for our next question. Our next question comes from the line of Eric Schmidt with Cantor. Your line is open.

Operator: Please stand by for our next question. Our next question comes from the line of Eric Schmidt with Cantor. Your line is open.

Speaker #2: Thanks, Mike. Congrats on all the progress as well. And unfortunately, another question for Sveta—she seems like she's on the hot seat today. So, I just want to be clear about what's in the 442 cumulative prescriptions that you're reporting.

Eric Schmidt: Thanks, Mike. Congrats on all the progress as well, unfortunately, another question for Tsveta. She seems like she's on the hot seat today. I just want to be clear about what's in the 442 cumulative prescriptions that you're reporting. Historically, I think you've said those are for individual patients mapped to individual start forms and wouldn't include refills or anything like that. Is that still the case?

Speaker #2: Historically, I think you've said those are for individual patients mapped to individual start forms and wouldn't include refills or anything like that. Is that still the case?

Speaker #3: Absolutely. They are unique patient prescriptions. In a way, that's kind of the equivalent of a start form. And it's written by a REM certified physician.

Tsveta Milanova: Absolutely. They are unique patient prescriptions. In a way, that's kind of the equivalent of a start form, and it's written by a REMS-certified physician.

Speaker #2: And I assume, Sveta, you have some insight into how many refills have also been written thus far?

Eric Schmidt: I assume, Tsveta, you have some insight into how many refills have also been written thus far?

Speaker #3: So yeah, the refill rates continue as patients reach their second and third month of therapy. The refills are continuing according to plan. Depending on the patients that have started and are progressing to the REMS, the refills are coming in.

Tsveta Milanova: Yeah, the refill rates continue as patients reach their second and third month of therapy. The refills are continuing according to plan. Depending on the patients that have started and are progressing to the REMS, the refills are coming in. We are not providing a specific kind of refill dynamics and total patients on therapy. As I said, moving forward, we'll move away from start forms and really start focusing on revenue more because it takes into account all of these dynamics that you're asking about, Eric. New patients start, time to treatment initiation, refills, and continuation.

Speaker #3: We are not providing a specific kind of refill dynamics and total patients on therapy. And as I said, moving forward, we'll move away from start forms and really start focusing on revenue more because it takes into account all of these dynamics that you're asking about, Eric.

Speaker #3: New patient starts, time to treatment initiations, refills, and continuation.

Speaker #2: Okay. You anticipated all of my questions. I just got one left, which is conversion of patients from start forms to therapy. Do you have a sense of whether there have been many or any patients who have dropped out of the queue, as they await therapy?

Eric Schmidt: Okay. You anticipated all of my questions. I've just got one left, which is conversion of patients from start forms to therapy. Do you have a sense of whether there have been many or any patients who have dropped out of the queue as they await therapy? Thanks.

Speaker #2: Thanks.

Tsveta Milanova: We have a very positive payer policies, and we have no market access hurdles. For now at the beginning of the launch, I'm very pleased with that. Our fill rate, which is basically prescriptions to patients starting on therapy, is very high, and it's very much in line with other rare diseases. Nothing unanticipated there. I'm very pleased with that very high conversion rate.

Speaker #3: We have a very positive payer policies. And we have no market access kind of hurdles for now. At the beginning of the launch, but I'm very pleased with that.

Speaker #3: Our feel rate, which is basically prescriptions to patients starting on therapy, is very high and it's very much in line with other rare diseases.

Speaker #3: So not nothing unanticipated there. So I'm very pleased with that very high conversion rate.

Speaker #2: Yeah. And Eric, I'll just add that this is, again, where our PKD experience smaller scale, but the experience really comes into play because it's usually a time element, not necessarily a loss element in the translation from a start form to a patient starting on therapy.

Brian Goff: Yeah. Eric, I'll just add that this is again, where our PKD experience, smaller scale, but the experience really comes into play because it's usually a time element, not necessarily a loss element in the translation from a start form to a patient starting on therapy. Again, we know with these NTD patients, as we move deeper into that penetration, it could take longer, which is why the translational aspect of going from a start form to revenue gets harder and harder from your perspective.

Speaker #2: And again, we know with these NTD patients, as we move deeper into that penetration, it could take longer which is why the translational aspect of going from a start form to revenue gets harder and harder from your perspective.

Speaker #2: Great. Thanks. And congrats again. Thanks a lot.

Tsveta Milanova: Great. Thanks and congrats again.

Eric Schmidt: Thanks a lot.

Speaker #3: Our next question comes from the line of Emily Botnar with HC Wainwright. Your line is open.

Operator: Our next question comes from the line of Emily Bodnar with H.C. Wainwright. Your line is open.

Speaker #5: Hi. Good morning. Thanks for your questions. And congrats also on the positive quarter. I'll ask on your sales for thalassemia. Were any of the two Q revenues driven by Europe specifically?

Emily Bodnar: Hi, good morning. Thanks for taking the question. Thanks and congrats also on the positive quarter. I'll ask on Europe sales for thalassemia. Were any of the Q2 revenues driven by Europe specifically? How do you think about ex-US revenue growth for the remainder of the year? Maybe secondly, with the sickle cell disease PDUFA coming in November, are you expecting to launch by year-end, and should we be expecting any kind of initial revenues for Q4? Thanks.

Speaker #5: And how do you kind of think about XUS revenue growth for the remainder of the year? And maybe secondly, with the sickle cell disease, could you come in in November?

Speaker #5: Are you expecting to launch by year-end? And should we be expecting any kind of initial revenues for the fourth quarter?

Speaker #2: Thanks, Emily. Cecilia can comment on the European question. And then we can come back to the question about sickle cell.

Brian Goff: Thanks, Emily. Cecilia can comment on the European question, and then we can come back to the question about sickle cell.

Speaker #6: Yeah. So Emily, the ex-U.S. revenue so far this quarter is a combination of the consistent, continued demand in DCC, as we have early access there, as well as anticipated demand for thalassemia in Europe following the approval in May.

Cecilia Jones: Yeah. Emily, the ex-US revenue so far this quarter is a combination of the consistent continued demand in GCC as we have early access there, as well as anticipated demand for thalassemia in Europe following the approval in May. I'd say the vast majority of our revenues are still expected to come from the US for the upcoming quarters as we're still ramping up the other regions, early access for both. We don't expect either one to be material contributors. The other question on sickle. Again, given the PDUFA date being November, it wouldn't be a material contribution to our full-year revenues for 2026.

Speaker #6: I'd say the vast majority of our revenues are still expected to come from the US. So the upcoming quarters, as we're still kind of ramping up the other regions, early access for both.

Speaker #6: So we don't expect either one to be material contributors. And then the other question on Sickle, again, given the PDUFA date being November, it wouldn't be a material contribution to Oxbryta revenues for 2026.

Speaker #2: And I will just add, Emily, we're enthusiastic about the opportunity for a priority review and the November 1st PDUFA date for sickle cell. And none of you will know this, but we're actually at a pretty important sickle cell KOL and community physician meeting.

Brian Goff: I will just add, Emily, we're enthusiastic about the opportunity of a priority review and 1 November PDUFA for sickle cell. None of you will know this, but we're actually at a pretty important sickle cell KOL and community physician meeting. The reason I bring that up is I'm really proud of the work that Tsveta and the team are doing to get ready for that launch, and we're certainly looking to amortize as much as we can from the progress we're making in thalassemia towards that launch as well.

Speaker #2: So the reason I bring that up is I'm really proud of the work that Sveta, the team, are doing to get ready for that launch.

Speaker #2: And we're certainly looking to amortize as much as we can from the progress we're making in thalassemia towards that launch as well. Thank you.

Emily Bodnar: Thank you.

Brian Goff: Thank you.

Speaker #3: Please stand by for our next question. Ladies and gentlemen, due to the interest of time, we ask that you limit yourself to one question, please.

Operator: Please stand by for our next question. Ladies and gentlemen, due to the interest of time, we ask that you limit yourself to one question, please. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Speaker #3: Our next question comes from the line of Salvine Richter with Goldman Sachs. Your line is open.

Speaker #6: Good morning. This is Lydia on for Salvine. Thanks so much for taking her question. And congrats on the progress. Could you just speak broadly to the current breakout between transfusion and non-transfusion-dependent patients and when you anticipate the non-transfusion population to make up a majority of patients on treatment?

[Analyst] (Goldman Sachs): Good morning. This is Lydia on for Salveen. Thanks so much for taking our question, and congrats on the progress. Could you just speak broadly to the current breakout between transfusion and non-transfusion-dependent patients and when you anticipate the non-transfusion population to make up a majority of patients on treatment? As a quick follow-up, once you reach that 10 to 12-week range, do you expect that to sort of be the run rate going forward? Thanks so much.

Speaker #6: And then as a quick follow-up, once you reach that 10 to 12-week range, do you expect that to sort of be the run rate going forward?

Speaker #6: Thanks so much.

Speaker #2: Sure. Thanks, Lydia. Sveta.

Brian Goff: Sure thing, Cecilia. Tsveta?

Brian Goff: Sure thing, Lydia. Tsveta?

Speaker #3: Absolutely. What we're seeing now is a growing proportion of the NTDT segment, as we've always said and as an anticipated, in the first quarter.

Tsveta Milanova: Absolutely. What we're seeing now is a growing proportion of the NTDT segment, as we've always said, and as anticipated. In Q1 and partly in Q2, a significant proportion of the patients were the TTDT patients, given they have more frequent interactions with the healthcare system and are in generally the more engaged patient population. We've seen a significant growth of the NTDT patients in Q2. We expect that to continue. If you look at our breakdown of our initial launch partners, we have about 4,000 patients that we are initially targeting, and about 50% of them are the NTDT patients. We'll continue to penetrate that segment, and we expect the 10 to 12-week average time to treatment initiations to stabilize and remain constant over time.

Speaker #3: And partly in the second quarter, a significant proportion of the patients were the TDT patients, given they have more frequent interaction with the healthcare system and are generally the more engaged patient population.

Speaker #3: We've seen a significant growth of the NTD patients in the second quarter. We expect that to continue. And if you look at our breakdown of the our initial launch process, we have about 4,000 patients that we are initially targeting and about 50% of them are the NTDT patients.

Speaker #3: So, we'll continue to penetrate that segment, and we expect the 10- to 12-week average time to treatment initiation to stabilize and remain constant over time.

Speaker #3: Thank you. Please stand by for our next question. Our next question comes from the line of Tess Romero with JP Morgan. Your line is open.

Operator: Thank you. Please stand by for our next question. Our next question comes from the line of Tessa Romero with J.P. Morgan. Your line is open.

Speaker #7: Hi, Brian and team. Thanks so much for taking our question. So as a matter of quick housekeeping, can you just remind us what is the right way to think about the LOE for midopivac?

Tessa Romero: Hi, Brian and team. Thanks so much for taking our question. As a matter of quick housekeeping, can you just remind us what is the right way to think about the LOE for mitapivat? Second, to double-click here, what is the right way to think about how cumulative scripts for PYRUKYND should evolve from end of Q2 to end of Q3? When might you be in a position to guide to revenues if script count will no longer be reported after Q3? Thank you.

Speaker #7: And then second, to double-click here, what is the right way to think about how cumulative scripts for Augvezmi should evolve from end of 2Q to end of 3Q?

Speaker #7: And then when might revenues if script count will no longer be reported after 3Q? Thank you.

Speaker #2: Okay. Thanks, Tess. First one will be quick. Midopivac, you could think of LOE as 2035 of composition of matter plus extensions. And there are additional potential for patent extensions beyond that.

Brian Goff: Okay. Thanks, Tess. First one will be quick. mitapivat, you could think of LOE as 2035 of composition of matter plus extensions. There are additional potential for patent extensions beyond that. The second one, which of course for where we go from Q2 to Q3 will be directional. We're not giving specific guidance, qualitatively, Tsveta, I think this will be similar to earlier comments you've made about further penetration.

Speaker #2: The second one, which of course for where we go from 2Q to 3rd Q will be directional, not we're not giving specific guidance, but qualitatively Sveta, I think this will be similar to earlier comments you've made about further penetration.

Speaker #3: Absolutely. As we look into the second half of the year, we're looking forward to continue to penetrate the NTDT segment. And as we know, these patients have less frequent visits to the healthcare providers.

Tsveta Milanova: Absolutely. As we look into the second half of the year, we're looking forward to continue to penetrate the NTDT segment. As we know, these patients have less frequent visits to the healthcare providers. With that in mind, we also anticipate time to treatment initiations to move into the 10 to 12-week range, which will be a key dynamic of the quarter. As well, we are reaching this important six-month point of treatment benefit evaluation. That's one of the main reasons we will start transitioning beyond Q3 into actually providing revenue rather than continuous prescriptions. Very importantly, we have an important date, 1 November, with the addition of the sickle cell disease launch. Hopefully that launch will provide more information of how we can characterize the evolution of the mitapivat franchise across indications. We will do that at the time of launch.

Speaker #3: And with that in mind, we also anticipate time to treatment initiations to move into the 10 to 12-week range, which will be a key dynamic of the quarter.

Speaker #3: As well, we are reaching this important six months point of treatment benefit evaluation. And that's one of the main reasons we'll start transitioning beyond Q3 into actually providing revenues rather than continued prescriptions very importantly.

Speaker #3: We have an important date, November 1st, with the addition of the sickle cell disease launch. And once we have hopefully that launch will provide more information of how we can characterize the evolution of the midopivac franchise across indications.

Speaker #3: But we'll do that at the time of launch.

Brian Goff: Cecilia, Tess snuck in a third question about guidance and when, do you want to comment on that one?

Speaker #2: And Cecilia, Tess snuck in a third question about guidance and when. So do you want to comment on that one?

Brian Goff: Cecilia, Tess snuck in a third question about guidance and when, do you want to comment on that one?

Speaker #3: Yeah. Yeah. So Tess, as Svetas mentioned, also with sickle cell coming on board, upon a potential approval in November, we look into the appropriate time to provide guidance for the franchise going forward.

Cecilia Jones: Yeah. Tess, as Tsveta mentioned, also with sickle cell coming on board upon potential approval in November, we'll look into the appropriate time to provide guidance for the franchise going forward.

Speaker #2: Good. Thank you.

Brian Goff: Good. Thank you.

Speaker #7: Thank you.

Cecilia Jones: Thank you.

Tessa Romero: Thank you.

Speaker #3: Thank you. And our final question comes from the line of Luca Essi with RBC Capital Markets. Your line is open.

Operator: Thank you. Our final question comes from the line of Luca Issi with RBC Capital Markets. Your line is open.

Speaker #8: Hi, team. This is Shelby on for Luca. And thanks for taking our question. Maybe on the commercial preparation for a potential launch in sickle cell, I believe this has a higher Medicaid mix versus thalassemia and PKD.

[Analyst] (RBC Capital Markets): Hi, team. This is Shelby on for Luca, and thanks for taking our question. Maybe on the commercial preparation for a potential launch in sickle cell. I believe this has a higher Medicaid mix versus thalassemia and PKD. One, is that correct? Two, how are you thinking about gross to net dynamics and net revenue per patient in sickle cell relative to your other existing commercial products? Also, does the Novo competitive dynamic factor into your pricing approach at all? Any color there much appreciated.

Speaker #8: So why is that correct? And two, how are you thinking about gross-to-net dynamics and net revenue per patient in sickle cell relative to your other existing commercial products?

Speaker #8: And also, does the Novo competitive dynamic factor into your pricing approach at all? Any color there? Much appreciated.

Speaker #3: Absolutely. We'll provide definitely more specifics on pricing at the time of approval. And that's going to be driven by the label and the competitive environment at the time.

Tsveta Milanova: Absolutely. We'll provide definitely more specifics on pricing at the time of approval, and that's going to be driven by the label and the competitive environment at the time. We'll continue to observe that moving forward. Of course, the sickle cell disease population has a higher Medicaid proportion, and that, by definition, has a mandatory rebate of 23%, which will drive the gross to net to a higher level compared to PKD and thalassemia. I can tell you we are super excited about the PDUFA date, and the team is ready for launch.

Speaker #3: And we'll continue to observe that moving forward. Of course, the sickle cell disease population has a higher Medicaid proportion. And that by definition has a mandatory rebate of 23%, which will drive the gross-to-net to a higher level compared to PKD and thalassemia.

Speaker #3: But I can tell you we're super excited about the PADUFA date and the team is ready for launch. Thank you. Ladies and gentlemen, at this time, I would like to turn the call back over to Brian Goff for closing remarks.

Operator: Thank you. Ladies and gentlemen, at this time, I would like to turn the call back over to Brian Goff for closing remarks.

Speaker #2: All right. Thanks, everyone, for your questions and for joining us today. Sveta, it was in the hot seat today, which we quite enjoy. So thanks a lot for that.

Brian Goff: All right. Thanks, everyone, for your questions and for joining us today. Tsveta was in the hot seat today, which we quite enjoy, so thanks a lot for that. To close, we're really pleased with the progress we made in Q2. That includes delivering on continued AQVESME launch momentum, advancing mitapivat toward a potential sickle cell disease approval, as we just discussed, strengthening our pipeline with cevidoplenib and AG-236, and maintaining the financial flexibility to execute. Ultimately, we enter the H2 of the year focused, disciplined, and confident in our ability to build long-term value for both patients and shareholders. Thanks a lot, and we look forward to speaking with you all soon.

Speaker #2: To close, we're really pleased with the progress we made in the second quarter. That includes delivering on continued Augvezmi launch momentum. Advancing midopivac toward a potential sickle cell disease approval, as we just discussed.

Speaker #2: Strengthening our pipeline with sevadapinib and AG236. And maintaining the financial flexibility to execute. So ultimately, we enter the second half of the year focused, disciplined, and confident in our ability to build long-term value for both patients and shareholders.

Speaker #2: So thanks a lot. And we look forward to speaking with you all soon.

Operator: Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.

Q2 2026 Agios Pharmaceuticals Inc Earnings Call

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Agios Pharmaceuticals

Earnings