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]

Financial Data and Key Metrics Changes - In Q1 2025, net PyroKine revenue was $8.7 million, a 6% increase compared to $8.2 million in Q1 2024 [30] - Revenue decreased by 19% compared to Q4 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [33] - Cost of sales for the quarter was $1.1 million, R&D expenses were $72.7 million, an increase of $4.1 million compared to Q1 2024, and SG&A expenses were $41.5 million, an increase of $10.5 million compared to the prior year [36] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in Q1 2025, translating to 136 net patients on therapy, also a 5% increase versus the prior quarter [31] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [34] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with approximately 6,000 adults diagnosed in the U.S., and the company estimates that PyroKine's initial launch focus will address about 65% of the adult thalassemia patient population [27][28] - The sickle cell disease community is estimated to include 120,000 to 135,000 individuals in the U.S. and EU5, with a global prevalence exceeding 3 million [13] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [7] - The company is preparing for a potential U.S. approval and launch of PyroKine for thalassemia in September 2025, followed by sickle cell disease in 2026 [6][16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming PDUFA date and the potential to serve patients with unmet needs in thalassemia and sickle cell disease [46][66] - The company is confident in its strong balance sheet, which provides financial independence to support potential launches and advance existing programs [37][39] Other Important Information - The company has a robust early and mid-stage pipeline, with plans to file an investigational new drug application for AG-236 targeting polycythemia vera in mid-2025 [9][20] - The company has engaged in disease state education campaigns to prepare for the launch of PyroKine, focusing on both patients and healthcare providers [24] Q&A Session Summary Question: Has the mid-cycle review happened, and what are the next steps? - Management confirmed that no advisory committee meeting is planned and that the regulatory review is ongoing, with strong engagement with the FDA [45][46] Question: How has the withdrawal of Oxbreda impacted trial recruitment? - Management noted that while the withdrawal was disappointing, it has not affected their clinical trial conduct, and they see a significant opportunity in the sickle cell market [48][49] Question: What are the plans for launching mitapivat ex-U.S.? - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [54][57] Question: Any changes in communication frequency with the FDA? - Management stated that communication with the FDA remains consistent, with no changes due to recent agency reshuffling [65][66] Question: Rationale for starting the Phase II tebapivat study in sickle cell? - Management expressed confidence in the unmet need for therapies in sickle cell disease and the potential to grow the patient population with multiple products [72][73] Question: Plans for marketing to non-transfusion dependent patients? - The company plans to focus on both transfusion-dependent and non-transfusion-dependent patients, emphasizing the value proposition of PyroKine for both groups [78] Question: Anticipated evolution of PyroKine's pricing? - Pricing decisions will be based on the value proposition of the label received, with positive feedback from payers regarding the product profile [98]

Q1 2025 Financial Results and Business Update May 1, 2025 1 Agios Conference Call Participants | TOPIC | PARTICIPANT | | --- | --- | | Introduction | Chris Taylor, VP Investor Relations and Corporate | | | Communications | | Business Update | Brian Goff, Chief Executive Officer | | R&D Update | Sarah Gheuens, M.D., Ph.D., Chief Medical Officer, | | | Head of R&D | | Commercial Update | Tsveta Milanova, Chief Commercial Officer | | First Quarter 2025 Financial Results | Cecilia Jones, Chief Financial Officer ...

Financial Data and Key Metrics Changes - In the first quarter of 2025, net PyroKine revenue was $8,700,000, a 6% increase compared to $8,200,000 in the first quarter of 2024 [32] - Revenue decreased by 19% compared to the fourth quarter of 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [32] - Cost of sales for the quarter was $1,100,000, R&D expenses were $72,700,000, an increase of $4,100,000 compared to the first quarter of 2024, and SG&A expenses were $41,500,000, an increase of $10,500,000 compared to the prior year quarter [34] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in the first quarter since the January label update, translating into 136 net patients on therapy, also a 5% increase versus the prior quarter [30] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [33] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with 67% of diagnosed patients in the U.S. having no approved therapies [12] - The company estimates that its initial launch focus will address approximately 65% of the adult thalassemia patient population [26] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [6] - The company is preparing for a potential approval and launch in thalassemia in the U.S. by September 7, 2025, followed by sickle cell disease in 2026 [5][6] - The company is focused on disease state education campaigns to prepare for the launch, emphasizing the importance of monitoring and management of thalassemia [23] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential approval and launch of PyroKine for thalassemia and the Phase III readout for sickle cell disease, viewing 2025 as a breakout year [38] - The company maintains a strong balance sheet with approximately $1,400,000,000 in cash, providing financial independence to support product launches and pipeline advancement [5][36] Other Important Information - The company has a robust early and mid-stage pipeline poised for clinical advancement, with significant expected events for 2025 [8] - The company has welcomed Krishnan Viswanathan as Chief Corporate Development and Strategy Officer to enhance corporate strategy and capital allocation [10] Q&A Session Summary Question: Confirmation about no advisory committee for the September PDUFA - Management confirmed that there is no advisory committee planned and that the regulatory review is ongoing, with strong engagement with the FDA [42][43] Question: Impact of Oxbreda withdrawal on sickle cell trial recruitment - Management noted that they have not observed changes in clinical trial conduct and emphasized the need for multiple therapeutic options for sickle cell disease [46][47] Question: Plans for launching mitapivat ex-U.S. - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [50][53] Question: Changes in communication frequency with the FDA - Management stated that communication with the FDA remains consistent and normal, with no changes due to recent agency reshuffling [63] Question: Rationale for starting Phase II tebapivat study in sickle cell - Management highlighted the large unmet medical need in sickle cell disease and the importance of having multiple therapy options for patients [66][69] Question: Anticipated evolution of PyroKine's pricing - Management indicated that pricing decisions will be based on the value proposition of the label received and expressed confidence in navigating pricing opportunities [94][95]