AGIOS PHARMACEUTICALS, INC. (AGIO)

Item 2.    Management’s Discussion and Analysis of Financial Condition and Results of Operations

Forward-looking Information

The following discussion of our financial condition and results of operations should be read in conjunction with our unaudited condensed consolidated financial statements as of June 30, 2026 and for the three and six months ended June 30, 2026 and 2025, and related notes included in Part I, Item 1 of this Quarterly Report on Form 10-Q, as well as the audited consolidated financial statements and notes and Management’s Discussion and Analysis of Financial Condition and Results of Operations, included in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the SEC on February 12, 2026. This Management’s Discussion and Analysis of Financial Condition and Results of Operations contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on current expectations, estimates, forecasts and projections, and the beliefs and assumptions of our management, and include, without limitation, statements with respect to our expectations regarding our research, development and commercialization plans and prospects, results of operations, selling, general and administrative expenses, research and development expenses, and the sufficiency of our cash for future operations. Words such as “aim,” “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “strategy,” “target,” “vision,” “will,” “would” or the negatives of these words and similar expressions are intended to identify these forward-looking statements, although not all forward-looking statements contain these identifying words. Readers are cautioned that these forward-looking statements are predictions and are subject to risks, uncertainties and assumptions that are difficult to predict. Therefore, actual results may differ materially and adversely from those expressed in any forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by our forward-looking statements are those discussed under the heading “Risk Factors” in Part II, Item 1A and elsewhere in this report, and in our Annual Report on Form 10-K for the year ended December 31, 2025. We undertake no obligation to revise the forward-looking statements contained herein to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law.

Overview

We are a commercial-stage biopharmaceutical company dedicated to redefining the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities, collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve.

The lead product candidate in our portfolio, mitapivat, is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias. Mitapivat is approved under the brand name AQVESME™ in the United States for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia. Mitapivat is approved under the brand name PYRUKYND®: in the United States for the treatment of hemolytic anemia in adults with PK deficiency; in the European Union, or EU, for the treatment of PK deficiency and for the treatment of non-transfusion dependent and transfusion dependent alpha- or beta-thalassemia in adult patients; in the Kingdom of Saudi Arabia for the treatment of adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia; in the United Arab Emirates for the treatment of non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in adult patients; and in Great Britain for the treatment of PK deficiency in adult patients.

We submitted a supplemental New Drug Application, or sNDA, for the U.S. accelerated approval of mitapivat in sickle cell disease, or SCD, in May 2026, which was accepted with priority review by the FDA and granted a Prescription Drug User Fee Act, or PDUFA, goal date of November 1, 2026. To support this accelerated approval pathway, we initiated REIGNITE, a phase 3 confirmatory trial designed to demonstrate the clinical benefit of mitapivat on reducing transfusion burden in patients with SCD aged 12 years or older. Additionally, in the second quarter of 2026 we filed for regulatory approval for SCD in the Kingdom of Saudi Arabia.

We are also developing (i) AG-181, our phenylalanine hydroxylase, or PAH, stabilizer for the potential treatment of phenylketonuria, or PKU; (ii) AG-236, an siRNA in-licensed from Alnylam Pharmaceuticals, Inc., or Alnylam, targeting the transmembrane serine protease 6, or TMPRSS6, gene for the potential treatment of polycythemia vera, or PV; and (iii) cevidoplenib, an oral spleen tyrosine kinase, or SYK, inhibitor in-licensed from Oscotec Inc., or Oscotec, for the potential treatment of immune thrombocytopenia, or ITP, and other autoimmune indications.

Oscotec License Agreement

On June 1, 2026, we entered into a license agreement with Oscotec, a South Korean biopharmaceutical company, under which Agios acquired the worldwide rights (subject to Oscotec’s right to opt-in to develop and commercialize cevidoplenib in South Korea) to develop, manufacture, and commercialize cevidoplenib as a potential treatment for ITP and other autoimmune

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indications. Because the acquired assets do not meet the definition of a business in accordance with ASC 805, Business Combinations, Agios will account for the agreement as an asset acquisition.

In accordance with the agreement, in the three months ended June 30, 2026, Agios made an up-front payment to Oscotec and recognized in-process research and development of $25.0 million, which was recorded in research and development expense within our Consolidated Statements of Operations and classified as investing activities within our Consolidated Statements of Cash Flows. In addition, Agios is responsible to pay up to $140.0 million in potential development and regulatory milestones in the U.S. and Europe, in addition to sales milestones as well as tiered royalties on future net sales, if any, of licensed products, which may be subject to specified reductions and offsets.

Sale of Oncology Business to Servier Pharmaceuticals, LLC (Servier) and Sale of Contingent Payments

In March 2021, we completed the sale of our oncology business to Servier Pharmaceuticals, LLC, or Servier. The transaction included the sale of our entire oncology business, including our clinical-stage product candidate vorasidenib, and included a royalty of 15% of U.S. net sales of vorasidenib from the first commercial sale of vorasidenib through loss of exclusivity, or the Vorasidenib Royalty Rights. The Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.

In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma Investments 2019 ICAV, or Royalty Pharma. The sale was contingent upon FDA approval of vorasidenib and other customary closing conditions.

Upon consummation of the sale in August 2024, Royalty Pharma acquired 100% of the Vorasidenib Royalty Rights payments made by Servier on account of up to $1.0 billion in U.S. net sales for each calendar year. In addition, any such Vorasidenib Royalty Rights payments made by Servier on account of U.S. net sales in each calendar year in excess of $1.0 billion will be split, with Royalty Pharma having the rights to a 12% earn-out on those excess payments and Agios retaining the rights to a 3% earn-out on those excess payments, or the Retained Earn-Out Rights. Royalty income related to the Retained Earn-Out Rights, if any, will be recognized in the period when realizable.

Financial Operations Overview

General

Since inception, our operations have primarily focused on organizing and staffing our company, business planning, raising capital, assembling our core capabilities in cellular metabolism and classical hematology, identifying potential product candidates, undertaking preclinical studies, conducting clinical trials, establishing a commercial infrastructure, preparing for and executing on the commercial launches of PYRUKYND® and AQVESME™ and, prior to the sale of our oncology business to Servier in March 2021, marketing TIBSOVO® and IDHIFA®. Through March 2021, we financed our operations primarily through proceeds from the sale of our royalty rights, commercial sales of TIBSOVO®, funding received from our collaboration agreements, private placements of our preferred stock, our initial public offering of our common stock and concurrent private placement of common stock to an affiliate of Celgene, and our follow-on public offerings. Following the sale of our oncology business to Servier in March 2021, we have financed and expect to continue to finance our operations primarily through cash on hand, potential royalty payments with respect to the Retained Earn-Out Rights, the actual and potential future sales of PYRUKYND® and AQVESME™ and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions. In addition, we may pursue opportunistic debt offerings, and equity or equity-linked offerings.

Additionally, since inception, we have historically incurred significant operating losses. Our net loss for the six months ended June 30, 2026 was $199.8 million and for the six months ended June 30, 2025 was $201.3 million. As of June 30, 2026, we had an accumulated deficit of $761.5 million. We expect to continue to incur significant expenses and net losses until such time we are able to report profitable results. We may never achieve or maintain profitability, and our net losses may fluctuate significantly from year to year. We expect that we will continue to incur significant expenses as we continue to advance and expand our commercialization activities for PYRUKYND® and AQVESME™; continue to advance clinical development and regulatory activities for mitapivat, AG-181, AG-236 and cevidoplenib; expand and protect our intellectual property portfolio, including by in-licensing or acquiring assets for pipeline growth; and hire additional commercial and development personnel.

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Revenues

Our wholly owned product, PYRUKYND®, received approval from the FDA on February 17, 2022, for the treatment of hemolytic anemia in adults with PK deficiency in the United States. Our wholly owned product, AQVESME™, received approval from the FDA on December 23, 2025, for the treatment of anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in the United States. Upon FDA approval of PYRUKYND® and AQVESME™ in the United States, we began generating product revenue from sales of PYRUKYND® and AQVESME™, respectively. We sell PYRUKYND® and AQVESME™ in the United States to a limited number of specialty distributors and specialty pharmacy providers. These customers subsequently resell PYRUKYND® and AQVESME™ to pharmacies or dispense PYRUKYND® and AQVESME™ directly to patients. In addition to distribution agreements with these customers, we enter into arrangements with healthcare providers and payors that provide for government-mandated and/or privately-negotiated rebates, chargebacks and discounts with respect to the purchase of PYRUKYND® and AQVESME™.

In July 2024, we entered into a distribution agreement, or the NewBridge Agreem

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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and the related notes and other financial information included elsewhere in this Annual Report on Form 10-K. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. You should review "Item 1A, Risk Factors" of this Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a commercial-stage biopharmaceutical company dedicated to redefining the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities, collaborating to develop and deliver innovative medicines with the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve.

The lead product candidate in our portfolio, mitapivat, is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias. Mitapivat is approved in the United States by the U.S. Food and Drug Administration, or FDA, under the brand name AQVESME™ for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia and in Saudi Arabia under the brand name PYRUKYND® for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. Mitapivat is also approved under the brand name PYRUKYND® in the United States by the FDA for the treatment of hemolytic anemia in adults with PK deficiency and in the European Union, or EU, and Great Britain for the treatment of PK deficiency in adults.

In December 2024, we announced that we submitted a marketing authorization application, or MAA, to the European Medicines Agency, or EMA, and a regulatory application to the United Arab Emirates health authorities for PYRUKYND® for the treatment of adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia. In October 2025, we announced that the Committee for Medicinal Products for Human Use, or the CHMP, of the EMA adopted a positive opinion for the new indication for PYRUKYND® in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia. The European Commission is reviewing the CHMP’s opinion, with the final decision expected in early 2026.

We will have a pre-supplemental New Drug Application, or sNDA, meeting with the FDA in the first quarter of 2026 and intend to submit a U.S. marketing application for mitapivat in sickle cell disease, or SCD, following that engagement.

In addition, we are evaluating mitapivat for the treatment of pediatric patients with PK deficiency. We are also developing (i) tebapivat, a novel PK activator, for the potential treatment of lower-risk myelodysplastic syndromes, or LR MDS, and SCD; (ii) AG-181, our phenylalanine hydroxylase, or PAH, stabilizer for the potential treatment of phenylketonuria, or PKU; and (iii) AG-236, an siRNA in-licensed from Alnylam Pharmaceuticals, Inc., or Alnylam, targeting the transmembrane serine protease 6, or TMPRSS6, gene for the potential treatment of polycythemia vera, or PV.

Alnylam License Agreement

On July 28, 2023, we entered into a license agreement with Alnylam under which we acquired the rights to develop and commercialize Alnylam’s novel preclinical siRNA targeting the TMPRSS6 gene, which we refer to as AG-236, as a potential disease-modifying treatment for patients with PV.

In accordance with the license agreement, we made an up-front payment to Alnylam and recognized in-process research and development of $17.5 million in the year ended December 31, 2023. We will also pay Alnylam for certain expenses associated with the development of AG-236, and these will be recorded in our consolidated statements of operations as incurred. Additionally, we are responsible to pay up to $130.0 million in potential development and regulatory milestones, in addition to sales milestones as well as tiered royalties on annual net sales, if any, of licensed products, which may be subject to specified reductions and offsets. In the year ended December 31, 2025, we achieved a regulatory milestone that triggered a $10.0 million payment to Alnylam, which was recorded in research and development expense within our consolidated statements of operations and classified as investing activities within our consolidated statements of cash flows. Because the acquired assets under the license agreement with Alnylam do not meet the definition of a business in accordance with Accounting Standards Codification, or ASC, 805, Business Combinations, we accounted for the agreement as an asset acquisition.

Sale of Oncology Business to Servier Pharmaceuticals, LLC (Servier) and Sale of Contingent Payments

On March 31, 2021, we completed the sale of our oncology business to Servier Pharmaceuticals, LLC, or Servier. The transaction included the sale of our entire oncology business, including our clinical-stage product candidate vorasidenib, for a payment of approximately $1.8 billion in cash at the closing, subject to certain adjustments, and a payment of $200.0 million in

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cash, if, prior to January 1, 2027, vorasidenib is granted new drug application, or NDA, approval from the FDA with an approved label that permits vorasidenib’s use as a single agent for the adjuvant treatment of patients with Grade 2 glioma that have an isocitrate dehydrogenase, or IDH, 1 or 2 mutation (and, to the extent required by such approval, the vorasidenib companion diagnostic test is granted an FDA premarket approval), or the Vorasidenib Milestone Payment, and a royalty of 15% of U.S. net sales of vorasidenib from the first commercial sale of vorasidenib through loss of exclusivity, or the Vorasidenib Royalty Rights. The Vorasidenib Milestone Payment and Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.

In August 2024, the FDA approved vorasidenib for adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, following surgery including biopsy, sub-total resection, or gross total resection. In September 2024, we received the Vorasidenib Milestone Payment from Servier and recognized income of $200.0 million within the milestone payment from gain on sale of oncology business line item in our consolidated statements of operations for the year ended December 31, 2024. In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma Investments 2019 ICAV, or Royalty Pharma, for $905.0 million in cash, or the Upfront Payment. The sale was contingent upon FDA approval of vorasidenib and other customary closing conditions.

Upon consummation of the sale in August 2024, Royalty Pharma acquired 100% of the Vorasidenib Royalty Rights payments made by Servier on account of up to $1.0 billion in U.S. net sales for each calendar year. In addition, any such Vorasidenib Royalty Rights payments made by Servier on account of U.S. net sales in each calendar year in excess of $1.0 billion will be split, with Royalty Pharma having the rights to a 12% earn-out on those excess payments and Agios retaining the rights to a 3% earn-out on those excess payments, or the Retained Earn-Out Rights. As a result of the sale, we recognized income of $889.1 million ($905.0 million net of fees of $15.9 million) within the gain on sale of contingent payments line item in our consolidated statements of operations for the year ended December 31, 2024. Royalty income related to the Retained Earn-Out Rights, if any, will be recognized in the period when realizable.

Financial Operations Overview

General

Since inception, our operations have primarily focused on organizing and staffing our company, business planning, raising capital, assembling our core capabilities in cellular metabolism and classical hematology, identifying potential product candidates, undertaking preclinical studies, conducting clinical trials, establishing a commercial infrastructure, preparing for and executing on the commercial launches of PYRUKYND® and AQVESME™ and, prior to the sale of our oncology business to Servier on March 31, 2021, marketing TIBSOVO® and IDHIFA®. Through March 31, 2021, we financed our operations primarily through proceeds from the sale of our royalty rights, commercial sales of TIBSOVO®, funding received from our collaboration agreements, private placements of our preferred stock, our initial public offering of our common stock and concurrent private placement of common stock to an affiliate of Celgene, and our follow-on public offerings. Following the sale of our oncology business to Servier on March 31, 2021, we have financed and expect to continue to finance our operations primarily through cash on hand, potential royalty payments with respect to the Retained Earn-Out Rights, the actual and potential future sales of PYRUKYND®, the potential future sales of AQVESME™ if successfully launched by us and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions. In addition, we may pursue opportunistic debt offerings, and equity or equity-linked offerings.

Additionally, since inception, we have historically incurred significant operating losses. Our net loss for the year ended December 31, 2025 was $412.8 million, our net income for the year ended December 31, 2024 was $673.7 million and our net loss for the year ended December 31, 2023 was $352.1 million. As of December 31, 2025, we had an accumulated deficit of $561.7 million. The net income we generated in the year ended December 31, 2024 was primarily due to the sale of the Vorasidenib Royalty Rights to Royalty Pharma and our receipt of the Vorasidenib Milestone Payment discussed above in Overview. We expect to continue to incur significant expenses and net losses until such time we are able to report profitable results. We may never achieve or maintain profitability, and our net losses may fluctuate significantly from year to year. We expect that we will continue to incur significant expenses as we continue to advance and expand our commercialization activities for PYRUKYND®; continue our commercialization activities for AQVESME™; continue to advance clinical development and regulatory activities for mitapivat, tebapivat, AG-181 and AG-236; expand and protect our intellectual property portfolio, including by in-licensing or acquiring assets for pipeline growth; and hire additional commercial and development personnel.

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Revenues

Our wholly owned product, PYRUKYND®, received approval from the FDA on February 17, 2022, for the treatment of hemolytic anemia in adults with PK deficiency in the United States. Upon FDA approval of PYRUKYND® in the United States, we began generating product revenue from sales of PYRUKYND®. We sell PYRUKYND® to a limited number of specialty distributors and specialty pharmacy providers, or collectively, the Customers. These Customers subsequently resell PYRUKYND® to pharmacies or dispense PYRUKYND® directly to patients. In addition to distribution agreements with Customers, we ente

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