Financial Performance - The net loss for the six months ended June 30, 2025, was $201.3 million, compared to a net loss of $177.7 million for the same period in 2024[92]. - As of June 30, 2025, the accumulated deficit stood at $350.2 million, indicating ongoing financial challenges[92]. - Total revenue for the three months ended June 30, 2025, was $12,455,000, an increase of $3,840,000 (44.6%) compared to $8,615,000 for the same period in 2024, driven by increased volume associated with PYRUKYND®[122]. - Total revenue for the six months ended June 30, 2025, was $21,181,000, an increase of $4,377,000 (26.0%) compared to $16,804,000 for the same period in 2024, also due to increased volume associated with PYRUKYND®[123]. - Total operating expenses for the three months ended June 30, 2025, were $139,511,000, an increase of $25,079,000 (21.9%) compared to $114,432,000 for the same period in 2024[124]. - Total operating expenses increased by $40.2 million for the six months ended June 30, 2025, primarily due to a $20.8 million rise in selling, general and administrative expenses and an $18.7 million increase in research and development expenses[125]. - Interest income, net for the six months ended June 30, 2025, was $30.6 million, compared to $17.0 million for the same period in 2024, representing an increase of 80.5%[129]. - Cash, cash equivalents, and marketable securities balance was $1.3 billion as of June 30, 2025[138]. - Net cash used in operating activities for the six months ended June 30, 2025, was $188.6 million, compared to $172.5 million for the same period in 2024[139]. - Cash provided by investing activities for the six months ended June 30, 2025, was $191.6 million, an increase from $161.8 million in the same period of 2024[141]. Product Development and Regulatory Milestones - PYRUKYND® received FDA approval on February 17, 2022, and has since begun generating product revenue from sales[93]. - A regulatory milestone payment of $10.0 million was triggered in Q2 2025 due to the license agreement with Alnylam[85]. - In August 2024, the FDA approved vorasidenib, leading to a recognized income of $200.0 million from the Vorasidenib Milestone Payment[88]. - The sale of Vorasidenib Royalty Rights to Royalty Pharma resulted in recognized income of $889.1 million in Q3 2024[89]. - The total potential payments under the license agreement with Alnylam could reach up to $130.0 million, including development and regulatory milestones[85]. - The company submitted an sNDA to the FDA for PYRUKYND® for treating adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia, with a PDUFA goal date of September 7, 2025[101]. - The company is evaluating PYRUKYND® in clinical trials for SCD and pediatric patients with PK deficiency[101]. - The company updated clinical trial protocols to include monthly monitoring of liver tests for the first six months of treatment due to potential hepatocellular injury risks[108]. - The phase 2 portion of the RISE UP study achieved its primary endpoint, with 46.2% of patients in the 50 mg twice daily mitapivat arm and 50.0% in the 100 mg twice daily arm achieving a hemoglobin response, compared to 3.7% in the placebo arm[109]. - The phase 3 portion of the RISE UP trial has enrolled over 200 patients worldwide, with topline data expected in late 2025 and a potential U.S. commercial launch in 2026 if approved[109]. - The company initiated a phase 2 clinical trial of tebapivat in adult patients with SCD in Q2 2025, following the completion of a phase 1 trial[112]. Research and Development Expenses - The company expects to continue incurring significant expenses as it advances clinical development for PYRUKYND® and other product candidates[92]. - Research and development expenses are expected to increase as product candidate development programs progress, reflecting the company's focus on innovation[98]. - Research and development expenses for the three months ended June 30, 2025, were $91,940,000, an increase of $14,539,000 (18.8%) compared to $77,401,000 for the same period in 2024[124]. - Total research and development expenses for the six months ended June 30, 2025, were $164.7 million, up from $146.0 million in the same period of 2024, reflecting an increase of $18.7 million[128]. - Direct research and development expenses increased by $11.9 million, primarily due to a $10.0 million milestone payment associated with an agreement with Alnylam[128]. Commercialization and Market Strategy - The company has entered into distribution agreements for PYRUKYND® in the Gulf Cooperation Council region and the European Economic Area[94]. - The company has entered into distribution agreements with NewBridge Pharmaceuticals and Avanzanite Bioscience for commercialization of PYRUKYND® in the Gulf Cooperation Council region and the European Economic Area, respectively[102]. - The company expects to incur significant commercialization expenses related to product sales, marketing, manufacturing, and distribution as it continues to commercialize PYRUKYND®[144]. Operational Challenges and Risks - The company may need to delay or limit product development or commercialization efforts if it cannot secure funding on favorable terms[148]. - The company faces operational delays and increased costs due to global economic and political developments, including rising energy prices[150]. - The company is exposed to interest rate sensitivity due to its investments primarily in short-term marketable securities, which could decrease in value if market interest rates increase[150]. - The company has contracts with CROs and contract manufacturing organizations in Asia and Europe, exposing it to foreign currency exchange rate fluctuations[151]. - The company has not hedged its foreign currency exchange rate risk and currently has minimal or no liabilities denominated in foreign currencies[151]. - The company may have to relinquish valuable rights to technologies or revenue streams if it raises funds through collaborations or licensing arrangements[147]. - The company is subject to costs and timing associated with regulatory reviews for its product candidates, including PYRUKYND® for thalassemia[147]. - The company must manage the costs of preparing and filing patent applications to maintain its intellectual property rights[147].

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]

Agios Pharmaceuticals shares have added about 14.2% since the beginning of the year versus the S&P 500's gain of 8.2%. What's Next for Agios Pharmaceuticals? While Agios Pharmaceuticals has outperformed the market so far this year, the question that comes to investors' minds is: what's next for the stock? There are no easy answers to this key question, but one reliable measure that can help investors address this is the company's earnings outlook. Not only does this include current consensus earnings expect ...

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]

[Business and Operational Highlights](index=1&type=section&id=Business%20and%20Operational%20Highlights) Agios reported strong PYRUKYND® commercial performance, advanced its R&D pipeline, and prepared for potential U.S. approval for thalassemia - The company is focused on the upcoming PDUFA goal date of September 7, 2025, for the potential U.S. approval of PYRUKYND for thalassemia[3](index=3&type=chunk) - Topline results from the RISE UP Phase 3 trial of mitapivat in sickle cell disease are expected by the end of the year, with a potential U.S. commercial launch in 2026[3](index=3&type=chunk)[5](index=5&type=chunk)[10](index=10&type=chunk) - Entered into a distribution agreement with Avanzanite Bioscience B.V. to commercialize PYRUKYND in the European Economic Area, the UK, and Switzerland[6](index=6&type=chunk) [Commercial Performance – PYRUKYND® (mitapivat)](index=1&type=section&id=Commercial%20Performance%20%E2%80%93%20PYRUKYND%C2%AE%20%28mitapivat%29) PYRUKYND® net revenue reached **$12.5 million** in Q2 2025, driven by steady growth in patient enrollment and therapy PYRUKYND® Q2 2025 Performance | Metric | Q2 2025 | Q2 2024 | QoQ Growth (vs Q1 2025) | | :--- | :--- | :--- | :--- | | Net Revenue | $12.5 million | $8.6 million | N/A | | Unique Patient Enrollments | 248 | N/A | 6% | | Patients on Therapy | 142 | N/A | 4% | [R&D Highlights](index=2&type=section&id=R%26D%20Highlights) R&D pipeline advanced with PYRUKYND's sNDA for thalassemia, progress in sickle cell and LR-MDS trials, and AG-236 IND clearance - **PYRUKYND (mitapivat):** - **Thalassemia:** sNDA under active FDA review with a PDUFA goal date of September 7, 2025 - **Sickle Cell Disease:** Topline Phase 3 (RISE UP) results on track for year-end 2025[10](index=10&type=chunk) - **Tebapivat:** - **Sickle Cell Disease:** Dosed the first patient in a Phase 2 trial - **Lower-risk Myelodysplastic Syndromes (LR-MDS):** Phase 2b trial enrollment is progressing, with completion targeted by the end of 2025[8](index=8&type=chunk)[10](index=10&type=chunk) - **Early Pipeline:** - Received Investigational New Drug (IND) clearance for AG-236, an siRNA targeting TMPRSS6 for treating polycythemia vera (PV)[10](index=10&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) Agios reported a **net loss of $112.0 million** in Q2 2025, driven by increased R&D and SG&A expenses, with **$1.3 billion** in cash Q2 2025 Key Financial Metrics (in millions, vs. Q2 2024) | Metric | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | Net Product Revenue | $12.5 million | $8.6 million | | R&D Expenses | $91.9 million | $77.4 million | | SG&A Expenses | $45.9 million | $35.5 million | | Net Loss | $112.0 million | $96.1 million | - The increase in R&D expenses was primarily due to a **$10.0 million** regulatory milestone payment to Alnylam for AG-236[13](index=13&type=chunk) - The increase in SG&A expenses was mainly attributable to increased commercial activities in preparation for the potential approval of PYRUKYND in thalassemia[13](index=13&type=chunk) - The company ended the quarter with **$1.3 billion** in cash, cash equivalents, and marketable securities, expected to fund operations, potential launches, and pipeline expansion[5](index=5&type=chunk)[13](index=13&type=chunk) [Financial Statements](index=5&type=section&id=Financial%20Statements) Consolidated financial statements show **$1.47 billion** in total assets and a **net loss of $112.0 million** for Q2 2025, or **($1.93)** per share [Consolidated Balance Sheet Data](index=5&type=section&id=Consolidated%20Balance%20Sheet%20Data) As of June 30, 2025, Agios reported **$1.34 billion** in cash, **$1.47 billion** in total assets, and **$1.37 billion** in stockholders' equity Consolidated Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $1,339,404 | $1,532,031 | | Total assets | $1,471,237 | $1,663,199 | | Stockholders' equity | $1,369,555 | $1,540,956 | [Consolidated Statements of Operations Data](index=5&type=section&id=Consolidated%20Statements%20of%20Operations%20Data) For Q2 2025, net product revenue was **$12.5 million**, with loss from operations at **$127.1 million** and a **net loss of $112.0 million**, or **($1.93)** per share Statement of Operations Summary (in thousands, except per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | | :--- | :--- | :--- | | Product revenue, net | $12,455 | $8,615 | | Total operating expenses | $139,511 | $114,432 | | Loss from operations | $(127,056) | $(105,817) | | Net loss | $(112,020) | $(96,118) | | Net loss per share | $(1.93) | $(1.69) |

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 will host a conference call and live webcast on July 31, 2025, at 8:00 a.m. ET to report its Q2 2025 financial results and business highlights [1] - The live webcast will be accessible on the company's website, with a replay available approximately two hours after the event [2] Company Overview - Agios Pharmaceuticals is a leader in pyruvate kinase (PK) activation, focusing on developing therapies for rare diseases [3] - The company markets a first-in-class PK activator for adults with PK deficiency, which is the first disease-modifying therapy for this condition [3] - Agios is advancing a clinical pipeline that includes investigational medicines for alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency, myelodysplastic syndrome (MDS)-associated anemia, and phenylketonuria (PKU) [3] - Additionally, Agios is developing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera [3]

Core Insights - Agios Pharmaceuticals has appointed Dr. Jay Backstrom to its Board of Directors, which is expected to enhance the company's strategic direction and clinical program advancements [1][2][3] Company Overview - Agios Pharmaceuticals is a leader in cellular metabolism and pyruvate kinase (PK) activation, focusing on therapies for rare diseases [1][4] - The company markets a first-in-class PK activator for adults with PK deficiency, representing the first disease-modifying therapy for this condition [4] Leadership and Expertise - Dr. Backstrom brings extensive experience from his previous roles, including President and CEO of Scholar Rock and Executive Vice President of Research and Development at Acceleron Pharma [2][3] - His leadership has been instrumental in advancing clinical programs to regulatory approval, particularly in rare diseases [2][3] Strategic Focus - Agios is focused on maximizing the potential of its PK activator, PYRUKYND (mitapivat), and advancing its pipeline of rare disease medicines [2][3] - The company is developing investigational medicines for conditions such as alpha- and beta-thalassemia, sickle cell disease, and myelodysplastic syndromes [4]

Company Overview - Agios Pharmaceuticals, Inc. is a leader in cellular metabolism and pyruvate kinase (PK) activation, focusing on therapies for rare diseases [3] - The company markets a first-in-class PK activator for adults with PK deficiency, representing the first disease-modifying therapy for this rare condition [3] - Agios is advancing a clinical pipeline that includes investigational medicines for alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency, myelodysplastic syndromes (MDS)-associated anemia, and phenylketonuria (PKU) [3] - Additionally, Agios is developing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera [3] Upcoming Events - The management team of Agios is scheduled to present at the Goldman Sachs 46th Annual Global Healthcare Conference on June 9, 2025, at 8:40 a.m. ET [1] - A live webcast of the presentation will be available on the company's website, with a replay archived for at least two weeks [2]