RISE UP Phase 3 Trial Results - Mitapivat met the primary endpoint with a 40.6% hemoglobin response rate, defined as ≥1.0 g/dL increase in average Hb from Week 24 through Week 52 compared to baseline, significantly higher than the 2.9% in the placebo arm[38] - There was a trend favoring mitapivat with a 14% reduction in the annualized rate of sickle cell pain crises (SCPCs) compared to placebo, although this did not reach statistical significance[39] - Mitapivat showed a statistically significant improvement in average change from baseline in hemoglobin concentration, with a 7.43 g/L difference compared to placebo[41] - Mitapivat significantly reduced the average change from baseline in indirect bilirubin compared to placebo, with a difference of -16.91 µmol/L[46] - The trial showed a trend in favor of mitapivat with a 14% reduction in the annualized rate of hospitalizations for SCPC compared to placebo[50] - Percent reticulocytes substantially decreased from baseline in the mitapivat arm vs placebo[52] Safety and Discontinuation - The safety profile observed in the RISE UP Phase 3 trial was consistent with previous mitapivat sickle cell disease trials, with no new safety signals identified[57] - The discontinuation rate in the double-blind treatment period was low, with 13% in the mitapivat arm and 18.8% in the placebo arm[34] Next Steps - The company intends to submit a marketing application for mitapivat in the U S for sickle cell disease after a pre-sNDA meeting with the FDA in Q1 2026[61, 68]

Core Insights - Agios Pharmaceuticals reported a narrower loss of $1.78 per share in Q3 2025, compared to the Zacks Consensus Estimate of a loss of $1.93, and a significant decline from earnings of $16.22 per share in the same quarter last year [1][6] - Total revenues for the third quarter reached $12.9 million, exceeding the Zacks Consensus Estimate of $10 million, and reflecting a 44% year-over-year increase [2][6] - The company's stock rose by 2.9% following the earnings report, and has increased by 31.5% year-to-date, outperforming the industry average increase of 10.6% [2] Financial Performance - Revenues were solely derived from product sales of Pyrukynd, Agios' only marketed drug, which is approved for treating hemolytic anemia in adults with pyruvate kinase deficiency [3] - Pyrukynd's sales increased by 3% sequentially, with 149 patients currently on the therapy in the U.S., marking a 5% increase from Q2 2025 [3] - Research and development expenses rose by approximately 19.7% year-over-year to $86.8 million, attributed to higher costs related to studies on the PK activation franchise [4] - Selling, general, and administrative expenses increased by 7.3% year-over-year to $41.3 million, driven by preparations for a potential approval and launch of Pyrukynd for thalassemia [7] Pipeline Developments - The FDA is expected to make a decision on Pyrukynd's thalassemia indication by December 7, 2025, following a positive opinion from the EMA [6][11] - The FDA extended the review timeline for Pyrukynd's supplemental new drug application by three months due to a request for a Risk Evaluation and Mitigation Strategy [9][10] - Agios has completed enrollment in the phase III RISE UP study for mitapivat in treating sickle cell disease, with top-line data expected by the end of 2025 [12] - The company is also developing tebapivat for myelodysplastic syndromes, with patient enrollment in a phase IIb study completed and top-line data expected in early 2026 [13]

Financial Data and Key Metrics Changes - In Q3 2025, Agios Pharmaceuticals reported net revenue of $12.9 million, a 44% increase compared to $9 million in Q3 2024, and a 3% increase from $12.5 million in Q2 2025 [8][6][9] - The cost of sales for the quarter was $1.7 million, while R&D expenses rose to $86.8 million, an increase of $14.3 million compared to the previous year [9][10] - SG&A expenses were $41.3 million, up $2.7 million year-over-year, reflecting disciplined investment ahead of potential product launches [9] Business Line Data and Key Metrics Changes - PYRUKYND net revenue was $12.9 million, reflecting strong commercial execution in PK deficiency ahead of potential U.S. approval for thalassemia [8][12] - 262 patients completed prescription enrollment forms, with 149 currently on therapy, marking a 5% increase from the second quarter [12][13] Market Data and Key Metrics Changes - Agios received approval for PYRUKYND in adults with thalassemia in Saudi Arabia, marking its first global regulatory approval for this indication [6][18] - A positive CHMP opinion was received for PYRUKYND in Europe, with a regulatory decision anticipated in early 2026 [18][19] Company Strategy and Development Direction - The company is focused on unlocking long-term shareholder value through multiple high-value catalysts, including the upcoming PDUFA date for PYRUKYND in thalassemia [5][6] - Agios is pursuing a capital-efficient global commercialization strategy through partnerships, retaining full rights to PYRUKYND while minimizing capital investment for U.S. launches [10][13] - The company aims to expand and diversify its pipeline through both internal efforts and external assets [10][28] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ability to deliver a successful launch for PYRUKYND in thalassemia, emphasizing the critical need for treatment innovation in the community [7][16] - The company anticipates continued revenue growth in 2025, driven by strong execution of its sales force [9][10] Other Important Information - Agios has approximately $1.3 billion in cash and investments, positioning it to invest in potential U.S. launches and advance its rare disease pipeline [6][10] - The company completed enrollment in the Phase 2b trial of tebapivat for lower-risk myelodysplastic syndromes, with top-line data expected early next year [9][24] Q&A Session Summary Question: What type of REMS program is the FDA interested in for thalassemia? - Management indicated that the REMS program will include monitoring and some form of education, but specific details cannot be disclosed at this time [33] Question: What type of business development makes sense for the company at this stage? - The company is looking for transformative therapies for rare diseases and is not tied to any specific timeline for transactions [34] Question: What are the liver monitoring requirements in Saudi Arabia and Europe? - In Saudi Arabia, monitoring is required once a month for the first six months, while the European label is still pending [41] Question: How is the commercial approach changing due to monitoring requirements? - Management does not anticipate REMS to be a barrier to prescribing, as both academic and community practices have experience with such programs [43] Question: What is the strategy for the European thalassemia launch with Avanzanite? - The pricing and reimbursement process in Europe can take 12 to 18 months post-approval, and the company is working closely with Avanzanite to refine its strategy [51]

Financial Performance - Q3 2025 net revenues reached $12.9 million, a 44% increase compared to $9.0 million in Q3 2024 [12] - Cash on hand remains strong at $1.3 billion, intended for investment in U S launches and pipeline development [10, 12, 15] - Net loss for Q3 2025 was $103.4 million, compared to a net income of $947.9 million in Q3 2024 [15] PYRUKYND® Commercial Progress - PYRUKYND net sales were $12.9 million in Q3 2025, compared to $12.5 million in Q2 2025 and $9.0 million in Q3 2024 [15, 20] - In the U S, 262 unique PK deficiency patients have completed prescription enrollment forms since launch [20] - There are 149 net patients on PYRUKYND treatment in the U S, including new prescriptions and treatment continuations [20] - PYRUKYND has been prescribed by 227 unique prescribers in the U S [20] Regulatory and Pipeline Advancements - PYRUKYND received SFDA approval in Saudi Arabia for thalassemia [12, 27, 28] - A positive CHMP opinion in Europe was received for PYRUKYND in thalassemia [12, 27, 28] - Enrollment is complete in the tebapivat Phase 2b trial for lower-risk MDS, with top-line data anticipated in early 2026 [12, 27]

Core Insights - Agios Pharmaceuticals reported financial results for Q3 2025, highlighting a focus on key milestones for its drug PYRUKYND in treating thalassemia and sickle cell disease [1][2]. Financial Performance - PYRUKYND generated $12.9 million in net revenues for Q3 2025, a 44% increase from $9.0 million in Q3 2024 and a 3% increase from $12.5 million in Q2 2025 [5][6]. - The company reported a net loss of $103.4 million for Q3 2025, compared to a net income of $947.9 million in Q3 2024, which was primarily due to a milestone payment and sale of royalty rights recorded in the previous year [7][17]. Product Development and Regulatory Updates - The PDUFA goal date for PYRUKYND's supplemental New Drug Application (sNDA) for thalassemia has been extended to December 7, 2025, due to a request for a Risk Evaluation and Mitigation Strategy (REMS) [6][11]. - The European Medicines Agency's CHMP has adopted a positive opinion for PYRUKYND in thalassemia, with a final decision expected by early 2026 [5][6]. - The RISE UP Phase 3 trial for sickle cell disease is expected to provide topline results by year-end 2025, potentially leading to a U.S. commercial launch in 2026 [5][11]. Research and Development - The Phase 2b trial for tebapivat in lower-risk myelodysplastic syndromes (MDS) has completed enrollment, with topline results anticipated in early 2026 [5][11]. - Research and Development expenses for Q3 2025 were $86.8 million, an increase of $14.3 million compared to Q3 2024, driven by higher clinical trial costs [11][17]. Cash Position - As of September 30, 2025, Agios had $1.3 billion in cash, cash equivalents, and marketable securities, down from $1.5 billion at the end of 2024 [5][11].

Financial Data and Key Metrics Changes - In Q2 2025, the company reported net revenue of $12.5 million, a 45% increase compared to $8.6 million in Q2 2024 and a 44% increase compared to $8.7 million in Q1 2025 [9][10] - The company ended Q2 2025 with approximately $1.3 billion in cash, cash equivalents, and marketable securities, indicating a strong financial position to support future growth [7][11] Business Line Data and Key Metrics Changes - The net revenue growth was attributed to strong commercial execution in Pyrokine, with an increase in the number of patients on active treatment [10][15] - The company dosed the first patient in the Phase II trial of tebapivat in sickle cell disease and received IND clearance for AG-236, targeting polycythemia vera [8][9] Market Data and Key Metrics Changes - The company anticipates a potential launch of Pyrokine for thalassemia in the U.S. pending FDA approval, with a PDUFA goal date set for September 7, 2025 [6][19] - The GCC market has an estimated 70,000 thalassemia patients, with a focus on Saudi Arabia for initial market entry [23][24] Company Strategy and Development Direction - The company aims to deliver sustainable growth and unlock long-term shareholder value through a capital-efficient commercial build-out and strategic investments in its pipeline [5][12] - The focus is on expanding the pipeline through internal efforts and business development activities, with a strong emphasis on rare disease treatments [13][32] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential to transform the treatment landscape for thalassemia and sickle cell disease with Pyrokine, highlighting the high unmet need in these patient populations [8][19] - The company is well-prepared for the potential launch of Pyrokine in thalassemia, with a robust commercial strategy and a dedicated sales force [21][56] Other Important Information - The company has entered into revenue-sharing agreements with Avanzanite Bioscience for commercialization in Europe and Newbridge Pharmaceuticals for the GCC, which are expected to favor Agios in the long term [12][22] - The company is actively engaging with healthcare professionals and patients to understand their needs better, which is crucial for the successful launch of Pyrokine [20][57] Q&A Session Summary Question: Any updates on ometipivat safety profile? - Management confirmed there are no new updates regarding the safety profile, including liver toxicity [36][37] Question: Insights on GCC approval dates? - Management indicated ongoing discussions across multiple regions and readiness for commercialization [38] Question: Are you in labeling discussions for thalassemia? - Management stated that updates to the PKD label are anticipated to reflect the new indication and dosing [43][46] Question: Expectations for SG&A spending? - Management expects some growth in SG&A expenses related to the thalassemia launch, with additional launch-related expenses anticipated upon approval [48][49] Question: Initial target patient population for thalassemia? - Management identified approximately 4,000 symptomatic patients as the initial target for the launch in the U.S. [55][56] Question: Pediatric opportunity for thalassemia? - Management plans to expand trials to the pediatric population once adult data is available [66][67] Question: Changes in sickle cell trial protocol? - Management confirmed that monitoring protocols have been aligned with previous findings to ensure patient safety [82][83] Question: Will hepatocellular injury be in the label? - Management indicated that the final label will be determined at the PDUFA date, with ongoing discussions with the FDA [88][92] Question: Prescriber base for thalassemia launch? - Management emphasized the importance of engaging both academic centers and community hematologists to address the unmet needs of thalassemia patients [96][98]

Financial Data and Key Metrics Changes - In Q2 2025, Agios Pharmaceuticals reported net revenue of $12.5 million, a 45% increase compared to $8.6 million in Q2 2024 and a 44% increase compared to $8.7 million in Q1 2025 [9][10] - The company ended the quarter with approximately $1.3 billion in cash, cash equivalents, and marketable securities, indicating a strong financial position to support future growth [6][11] Business Line Data and Key Metrics Changes - The net revenue growth in the second quarter was attributed to strong commercial execution in pyruvate kinase deficiency (PKD) and an increase in the number of units processed directly by specialty pharmacies [10][14] - The company anticipates continued variability in net revenues due to ordering patterns, especially with the upcoming focus on thalassemia treatment [10][11] Market Data and Key Metrics Changes - As of Q2 2025, 248 patients completed prescription enrollment forms, a 6% increase from the previous year, with 142 patients actively receiving treatment, reflecting a 4% sequential increase [15] - The company is preparing for a potential launch in thalassemia, with a focus on the 4,000 patients actively managed due to their symptoms [19][53] Company Strategy and Development Direction - Agios aims to deliver sustainable growth and unlock long-term shareholder value through the commercialization of Pyrokine and the advancement of its pipeline [4][30] - The company has entered into revenue-sharing agreements with Avanzanite Bioscience for Europe and Newbridge Pharmaceuticals for the GCC, allowing for capital-efficient commercialization strategies [12][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential to transform the treatment landscape for thalassemia and sickle cell disease with Pyrokine, pending FDA approval [5][8] - The company is focused on building a diversified rare disease portfolio and advancing its PK activator franchise across multiple indications [31][30] Other Important Information - The company has received IND clearance for AG-236, an siRNA targeting TMPRSS6 for polycythemia vera, and has dosed the first patient in the Phase II trial of tebapivat in sickle cell disease [7][29] - Agios is actively engaging with healthcare professionals and patients to understand their needs and prepare for the upcoming product launches [18][54] Q&A Session Summary Question: Any updates on ometipivat safety profile? - Management confirmed there are no new updates regarding the safety profile [36] Question: Insights on GCC approval dates? - Management indicated ongoing discussions across multiple regions and readiness for commercialization [37] Question: Are you in labeling discussions for thalassemia? - Management stated that updates to the PKD label are anticipated to reflect the new indication and dosing [44] Question: Expectations for SG&A spending? - Management expects some growth in SG&A expenses related to the thalassemia launch, with additional launch-related expenses anticipated upon approval [46] Question: Initial target patient population for thalassemia? - The initial focus will be on approximately 4,000 patients who are actively managed due to their symptoms [52] Question: Pediatric opportunity for thalassemia? - Management confirmed a high unmet need in pediatric patients and plans to run trials once adult data is available [64] Question: Changes in sickle cell trial protocol? - Management confirmed that monitoring protocols have been updated to align with safety concerns identified in other trials [81] Question: Will hepatocellular injury be in the label? - Management indicated that the final label will be determined at the PDUFA date, with ongoing discussions with the FDA [90]

Financial Performance - PYRUKYND net revenues reached $12.5 million in Q2 2025, a 44% increase compared to $8.7 million in Q1 2025 and a 45% increase compared to $8.6 million in Q2 2024[10] - The company maintains a strong financial position with $1.3 billion in cash on hand[9, 10, 14] - Net loss for Q2 2025 was $112.0 million, compared to a net loss of $96.1 million for Q2 2024[14] Pipeline Development - First patient dosed in Phase 2 Sickle Cell Disease trial for AG-236 after receiving IND clearance[11] - RISE UP Phase 3 trial in sickle cell disease is expected to have topline data by the end of 2025[37] - Tebapivat Phase 2b trial for LR-MDS is ongoing, with topline results expected in early 2026[9, 45] Commercialization - 248 unique PK deficiency patients completed prescription enrollment forms since launch in the U S [21] - 142 patients are on treatment in the U S , including new prescriptions and treatment continuations, with 215 unique prescribers[22] - The company anticipates a potential U S launch of PYRUKYND for thalassemia in Q3 2025, with a PDUFA goal date of September 7, 2025[11, 23, 24] Strategic Partnerships - Announced a commercialization and distribution partnership with Avanzanite Bioscience in Europe[10] - A commercialization and distribution agreement is in place with NewBridge for the GCC region, with anticipated first regulatory approval in the coming months[30]

Core Viewpoint - Agios Pharmaceuticals reported its financial results for Q2 2025, highlighting progress in its drug pipeline, particularly with PYRUKYND for thalassemia and ongoing trials for sickle cell disease [1][2]. Financial Performance - The company generated $12.5 million in net revenue for Q2 2025, an increase from $8.6 million in Q2 2024 [6][11]. - The net loss for Q2 2025 was $112.0 million, compared to a net loss of $96.1 million in Q2 2024 [7][17]. - As of June 30, 2025, Agios had $1.3 billion in cash, cash equivalents, and marketable securities, down from $1.5 billion at the end of 2024 [11][14]. Product Development and Pipeline - PYRUKYND's supplemental New Drug Application (sNDA) for thalassemia is under active review by the FDA, with a PDUFA goal date of September 7, 2025 [5][6]. - The topline results from the RISE UP Phase 3 trial for PYRUKYND in sickle cell disease are expected by year-end 2025, with a potential U.S. commercial launch in 2026 [5][6]. - The first patient has been dosed in the Phase 2 trial for tebapivat in sickle cell disease, which is currently enrolling patients [11]. Operational Highlights - There was a 6% increase in unique patients completing prescription enrollment forms compared to Q1 2025, totaling 248 patients [6]. - The number of patients on PYRUKYND therapy increased by 4% over Q1 2025, reaching 142 patients [6]. - Agios entered into a distribution agreement with Avanzanite Bioscience B.V. to commercialize PYRUKYND across the European Economic Area, the UK, and Switzerland [6]. Research and Development Expenses - R&D expenses for Q2 2025 were $91.9 million, up from $77.4 million in Q2 2024, primarily due to a $10 million regulatory milestone payment [11][17]. - Selling, General and Administrative (SG&A) expenses increased to $45.9 million in Q2 2025 from $35.5 million in Q2 2024, attributed to increased commercial activities [11][17]. Strategic Vision - Agios aims to redefine the future of rare disease treatment by developing innovative medicines that can transform patients' lives [9].

Core Insights - Agios Pharmaceuticals is presenting new data on its pyruvate kinase (PK) activators, mitapivat and tebapivat, at the upcoming European Hematology Association (EHA) Congress in Milan, Italy, from June 12-15, 2025 [1][2] Company Overview - Agios Pharmaceuticals is a leader in cellular metabolism and PK activation, focusing on therapies for rare diseases [1][17] - The company has developed PYRUKYND (mitapivat), a first-in-class pyruvate kinase activator for treating hemolytic anemia in adults with PK deficiency [9][17] Clinical Data Presentation - A total of 14 presentations and publications will be shared at EHA 2025, highlighting the efficacy and safety of PK activation in treating rare blood disorders [3][2] - Key presentations include: - Results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children with PK deficiency, showing a clinically meaningful reduction in transfusion burden [6] - Long-term data from the ESTIMATE Phase 2 trial of mitapivat in sickle cell disease, demonstrating sustained efficacy and tolerability over three years [6] - Preclinical data on tebapivat's potential in reducing red blood cell sickling in sickle cell disease patients [6] Research Focus Areas - The presentations will cover serious conditions with limited treatment options, including sickle cell disease, thalassemia, PK deficiency, and myelodysplastic syndromes [2][6] - Ongoing investigations include the expression patterns of PKM2 in patients with myelodysplastic syndromes, supporting the potential of tebapivat in lower-risk MDS [6] Collaboration and Community Engagement - Agios aims to strengthen its collaboration with the global hematology community through these presentations at EHA [2]