AGIOS PHARMACEUTICALS, INC.
AGIOBusiness Summary
Agios Pharmaceuticals, Inc. is a commercial-stage biopharmaceutical company focused on redefining rare disease treatment, with a foundation in hematology and expertise in cellular metabolism. The company generates revenue through its approved products and is advancing a pipeline of rare disease medicines. Its core business model involves developing and commercializing innovative medicines, with a mix of product sales and potential milestone and royalty income from collaborations 1. The primary customer segments for its approved products are specialty distributors and specialty pharmacy providers in the United States, and distribution partners in other regions 2.
The company's lead product candidate, mitapivat, is an activator of pyruvate kinase (PK) enzymes for the potential treatment of hemolytic anemias. Mitapivat is approved in the United States under the brand name AQVESME™ for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia 3. It is also approved under the brand name PYRUKYND® in the United States for the treatment of hemolytic anemia in adults with PK deficiency, and in the European Union (EU) and Great Britain for the treatment of PK deficiency in adults 4. In Saudi Arabia, PYRUKYND® is approved for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia 5. The company commercially launched AQVESME™ in the United States in late January 2026 6.
Agios is also developing tebapivat, a novel PK activator, for the potential treatment of lower-risk myelodysplastic syndromes (LR MDS) and sickle cell disease (SCD) 7. AG-181, a phenylalanine hydroxylase (PAH) stabilizer, is being developed for the potential treatment of phenylketonuria (PKU) 8. Additionally, AG-236, an siRNA targeting the transmembrane serine protease 6 (TMPRSS6) gene, is in development for the potential treatment of polycythemia vera (PV) 9.
For the fiscal year ended December 31, 2025, total revenue was $54.028 million 10. This comprised U.S. product revenue of $49.170 million 11 and rest of world product revenue of $4.858 million 12. Cost of sales for the period was $6.345 million 13. Research and development expenses totaled $339.535 million 14, and selling, general and administrative expenses were $180.280 million 15. The company reported a net loss of $412.781 million 16 and a diluted EPS of $(7.12) 17. As of December 31, 2025, cash and cash equivalents were $89.130 million 18, and marketable securities totaled $1.075 billion 19 (current marketable securities of $765.295 million 20 plus non-current marketable securities of $310.013 million 21). The company's accumulated deficit as of December 31, 2025, was $561.705 million 22.
Comparing 2025 to 2024, total revenue increased by $17.5 million 23, driven by a $12.8 million 24 increase in U.S. product revenue due to increased PYRUKYND® volume and a $4.7 million 25 increase in rest of world product revenue from the Avanzanite Agreement. Total operating expenses increased by $63.9 million 26, primarily due to a $38.2 million 27 increase in research and development expenses and a $23.5 million 28 increase in selling, general and administrative expenses, the latter driven by preparations for AQVESME™ approval. The net loss in 2025 of $412.781 million 29 contrasts with a net income of $673.725 million 30 in 2024, with the 2024 income primarily attributable to the $889.1 million 31 gain on sale of contingent payments and the $200.0 million 32 Vorasidenib Milestone Payment.
During 2025, the FDA approved AQVESME™ for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in December 2025 33, with a commercial launch in the United States in late January 2026 34. The Saudi Food and Drug Authority approved PYRUKYND® for the treatment of adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in August 2025 35. The CHMP of the EMA adopted a positive opinion for a new indication for PYRUKYND® in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia in October 2025 36, with a final decision expected in early 2026 37. In November 2025, the phase 3 portion of the RISE UP trial for mitapivat in SCD achieved its primary endpoint of hemoglobin response, with 40.6% of patients in the mitapivat arm achieving a response compared to 2.9% in the placebo arm 38. The annualized rate of SCPCs was 2.62 in the mitapivat arm and 3.05 in the placebo arm, not achieving statistical significance for that primary endpoint 39. The ACTIVATE-kids trial for pediatric PK deficiency met its primary endpoint of hemoglobin response, with 31.6% of patients in the mitapivat arm achieving a response compared to 0% in the placebo arm 40. The ACTIVATE-kidsT trial for regularly transfused pediatric PK deficiency patients did not meet its primary endpoint of transfusion reduction response using Bayesian methodology 41, with 28.1% of patients in the mitapivat arm achieving the primary endpoint compared to 11.8% in the placebo arm 42. A regulatory milestone for AG-236 triggered a $10.0 million 43 payment to Alnylam in 2025 44. The phase 1 clinical trial of AG-181 in healthy volunteers was completed in December 2025 45.
Business Outlook
The European Commission is reviewing the CHMP's positive opinion for PYRUKYND® in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia, with a final decision expected in early 2026 46. The company plans to have a pre-supplemental New Drug Application (sNDA) meeting with the FDA in the first quarter of 2026 47 and intends to submit a U.S. marketing application for mitapivat in sickle cell disease (SCD) following that engagement 48.
A major growth area for the company is the expansion of its PK activator franchise, particularly mitapivat, across multiple hemolytic anemias. Mitapivat is being evaluated for the treatment of pediatric patients with PK deficiency 49. The company also expects to initiate a phase 1b proof of mechanism trial of AG-181 in patients with PKU in the first half of 2026 50 and confirm proof of mechanism in the second half of 2026 51. For AG-236, a phase 1 clinical trial in healthy volunteers was initiated in July 2025 52, and topline data for this trial are expected in the first half of 2026 53.
Regarding operational outlook, the company expects to continue to incur significant expenses and net losses until it is able to report profitable results 54. Research and development costs related to its portfolio are expected to increase as product candidate development programs progress 55. Selling, general and administrative expenses are also anticipated to increase to support continued research and development activities and ongoing and future commercialization activities, including the hiring of additional personnel 56. The company has updated its mitapivat clinical trial protocols across all indications to incorporate monthly monitoring of liver tests for the first six months of treatment, following observations of hepatocellular injury in the ENERGIZE and ENERGIZE-T trials 57.
Planned capital allocation includes funding future development and commercialization costs related to PYRUKYND® and AQVESME™ 58. The company expects its existing cash, cash equivalents, and marketable securities as of December 31, 2025, together with anticipated product revenue and interest income, to provide the financial independence to commercially launch AQVESME™ in the United States, prepare for the potential U.S. commercial launch of mitapivat in SCD, advance existing clinical programs, and opportunistically expand its pipeline through both internally and externally discovered assets 59. The company may also pursue opportunistic debt offerings, and equity or equity-linked offerings 60. Under the license agreement with Alnylam, the company may be required to pay up to an additional $120.0 million 61 in potential development and regulatory milestones, in addition to sales milestones and tiered royalties on annual net sales, if any, of licensed products 62.
The company explicitly flagged several structural headwinds and execution risks. These include the possibility that PYRUKYND® or AQVESME™ may be less effective than previously believed or cause undesirable side effects not previously identified, which could compromise marketability 63. The USPI for AQVESME™ contains a boxed warning regarding the potential for hepatocellular injury, and it is available only through a REMS program 64. Failure to comply with REMS requirements could result in regulatory action or decreased sales 65. The company also faces substantial competition from major pharmaceutical and biotechnology companies, academic institutions, and governmental agencies 66. Competitors may develop more effective, safer, more convenient, or less costly products, or obtain regulatory approval more rapidly 67. The company is singularly focused on rare diseases, making it more susceptible to changing market conditions specific to these markets 68. Furthermore, the company relies on third parties for manufacturing and supply, and any performance failure could delay development or commercialization 69. Geopolitical events, such as war, could negatively impact the ability to initiate, enroll, and retain patients in clinical trials 70. Changes in U.S. trade policy, including tariffs, could negatively impact costs of materials, production processes, and supply chain 71.
Risk Factors
The company faces material risks including the potential for PYRUKYND® or AQVESME™ to be less effective or cause undesirable side effects not previously identified, which could compromise marketability, as evidenced by the boxed warning for hepatocellular injury in AQVESME™'s USPI and the requirement for a REMS program 72. The company is singularly focused on rare diseases, making it more susceptible to market fluctuations specific to these patient populations 73. Competition is substantial, with numerous large pharmaceutical and biotechnology companies developing products for the same indications, potentially leading to more effective, safer, or cheaper alternatives, or faster regulatory approvals 74. Geopolitical events and trade policy changes, such as U.S. tariffs on imports, could disrupt supply chains, increase costs, and delay product development or commercialization 75. Non-compliance with U.S. and foreign export control, import, sanctions, anti-corruption, and anti-money laundering laws could lead to criminal and/or civil liability, including significant fines and penalties 76. The company's ability to use its net operating loss carryforwards and other tax attributes may be limited by ownership changes or regulatory changes 77.
Management Priorities
Management's message to shareholders emphasizes building a sustainable, value-creating company grounded in expertise in cellular metabolism and classical hematology, with a focus on developing and delivering innovative medicines for patients. They believe their proven PK activator franchise has the potential to become the standard of care across multiple hemolytic anemias, supported by approved indications in PK deficiency and thalassemia. Management also sees significant opportunity to unlock further value through a robust early- and mid-stage pipeline and believes the company has a clear path to profitability supported by its existing commercial portfolio. The company's strategic priorities include the successful commercialization of PYRUKYND® and AQVESME™ for approved indications, advancing existing clinical programs for mitapivat, tebapivat, AG-181, and AG-236, and opportunistically expanding the pipeline through both internally and externally discovered assets. Management expects to have a pre-sNDA meeting with the FDA in the first quarter of 2026 78 and intends to submit a U.S. marketing application for mitapivat in sickle cell disease following that engagement 79. The European Commission's final decision on the new indication for PYRUKYND® in thalassemia is expected in early 2026 80.
View Source Annual Report on SEC.gov ↗
References
- [1] Item 7, MD&A — Financial Operations Overview
- [2] Item 7, MD&A — Product Revenue
- [3] Item 1, Business — Business Overview
- [4] Item 1, Business — Business Overview
- [5] Item 1, Business — Business Overview
- [6] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [7] Item 1, Business — Business Overview
- [8] Item 1, Business — Business Overview
- [9] Item 1, Business — Business Overview
- [10] Item 7, MD&A — Revenues
- [11] Item 7, MD&A — Revenues
- [12] Item 7, MD&A — Revenues
- [13] Item 7, MD&A — Total Operating Expenses
- [14] Item 7, MD&A — Total Operating Expenses
- [15] Item 7, MD&A — Total Operating Expenses
- [16] Item 7, MD&A — Net (Loss) Income
- [17] Item 7, MD&A — Net (Loss) Income
- [18] Item 7, MD&A — Sources of Liquidity
- [19] Item 7, MD&A — Sources of Liquidity
- [20] Item 7, MD&A — Sources of Liquidity
- [21] Item 7, MD&A — Sources of Liquidity
- [22] Item 7, MD&A — Financial Operations Overview
- [23] Item 7, MD&A — Total Revenue – 2025 vs. 2024
- [24] Item 7, MD&A — Total Revenue – 2025 vs. 2024
- [25] Item 7, MD&A — Total Revenue – 2025 vs. 2024
- [26] Item 7, MD&A — Total Operating Expenses – 2025 vs. 2024
- [27] Item 7, MD&A — Total Operating Expenses – 2025 vs. 2024
- [28] Item 7, MD&A — Total Operating Expenses – 2025 vs. 2024
- [29] Item 7, MD&A — Net (Loss) Income
- [30] Item 7, MD&A — Net (Loss) Income
- [31] Item 7, MD&A — Other Income and Expense – 2025 vs. 2024
- [32] Item 7, MD&A — Other Income and Expense – 2025 vs. 2024
- [33] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [34] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [35] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [36] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [37] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [38] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [39] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [40] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [41] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [42] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [43] Item 1, Business — Alnylam License Agreement
- [44] Item 1, Business — Alnylam License Agreement
- [45] Item 1, Business — Other Programs
- [46] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [47] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [48] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [49] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [50] Item 1, Business — Other Programs
- [51] Item 1, Business — Other Programs
- [52] Item 1, Business — Other Programs
- [53] Item 1, Business — Other Programs
- [54] Item 7, MD&A — Financial Operations Overview
- [55] Item 7, MD&A — Research and Development Expenses
- [56] Item 7, MD&A — Selling, General and Administrative Expenses
- [57] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [58] Item 1, Business — PYRUKYND®/AQVESME™ (mitapivat): First-in-Class PK Activator
- [59] Item 7, MD&A — Funding Requirements
- [60] Item 7, MD&A — Funding Requirements
- [61] Item 7, MD&A — Contractual Obligations
- [62] Item 7, MD&A — Contractual Obligations
- [63] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [64] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [65] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [66] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [67] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [68] Item 1A, Risk Factors — Risks Related to Our Financial Position
- [69] Item 1A, Risk Factors — Risks Related to Our Dependence on Third Parties
- [70] Item 1A, Risk Factors — Risks Related to the Discovery, Development, and Commercialization of our Products and Product Candidates
- [71] Item 1A, Risk Factors — Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters
- [72] Item 1A, Risk Factors — PYRUKYND®, AQVESME™ or any of our product candidates that may receive marketing approval in the future, may fail to achieve the degree of market acceptance by physicians, patients, healthcare payors and others in the medical community necessary for commercial success.
- [73] Item 1A, Risk Factors — We face challenges as a less diversified company.
- [74] Item 1A, Risk Factors — We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.
- [75] Item 1A, Risk Factors — Changes in and uncertainty surrounding U.S. trade policy could have a material adverse impact on our business, financial condition and results of operations.
- [76] Item 1A, Risk Factors — We are subject to U.S. and foreign export control, import, sanctions, anti-corruption and anti-money laundering laws with respect to our operations, and non-compliance with such laws can subject us to criminal and/or civil liability and harm our business.
- [77] Item 1A, Risk Factors — Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
- [78] Item 7, MD&A — Overview
- [79] Item 7, MD&A — Overview
- [80] Item 7, MD&A — Overview
Analysis on 5/22/2026