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 AQVESMETM 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

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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 AQVESMETM 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 AQVESMETM 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 AQVESMETM; 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 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®.

In July 2024, we entered into a distribution agreement, or the NewBridge Agreement, with NewBridge Pharmaceuticals FZ-LLC, or NewBridge, pursuant to which we granted NewBridge the right to commercialize PYRUKYND® in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates, also known as the Gulf Council Countries, or GCC. In June 2025, we entered into a distribution agreement, or the Avanzanite Agreement, with Avanzanite Bioscience B.V., or Avanzanite, pursuant to which we granted Avanzanite the right to commercialize PYRUKYND® in the European Economic Area, Switzerland, and the U.K. For further discussion of our revenue recognition policy, see Note 2, Summary of Significant Accounting Polices and Note 8, Product Revenue, to the consolidated financial statements in this Annual Report on Form 10-K.

In the future, we expect to continue to generate revenue from product sales of PYRUKYND®. We commercially launched AQVESMETM in the United States in late January 2026 and we anticipate generating revenue from product sales of AQVESMETM in the future. We may also generate revenue from milestone payments, upfront payments or royalties on product sales under collaborations or licensing agreements that we may enter into in the future.

Cost of Sales

Cost of sales consists primarily of manufacturing costs for sales of PYRUKYND®. Based on our policy to expense costs associated with the manufacturing of our products prior to regulatory approval, certain of the manufacturing costs associated with product shipments of PYRUKYND® recorded during the years ended December 31, 2025, December 31, 2024 and December 31, 2023 were expensed prior to February 17, 2022, and, therefore, are not included in costs of sales during the years ended December 31, 2025, December 31, 2024 and December 31, 2023. The amounts excluded from cost of sales were not significant during the years ended December 31, 2025, December 31, 2024 and December 31, 2023.

Inventories are reviewed periodically to identify excess or obsolete inventory based on projected sales activity as well as product shelf-life. Expired inventory is disposed of, and the related costs are recognized as cost of sales in our consolidated statements of operations, when, based on the expiry date, we do not believe we are able to sell the inventory. We have not reserved for excess or obsolete inventory during the years ended December 31, 2025 and December 31, 2024.

Research and Development Expenses

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect research and development costs related to our portfolio to increase as our product candidate development programs progress. However, the successful development of our product candidates is highly uncertain. As such, at this time, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts that will be necessary to complete the development of and to commercialize these product candidates. We are unable to predict the amount of net cash inflows from any of our products or product candidates. This is due to the numerous risks and uncertainties associated with developing medicines, including the uncertainty of:

•establishing an appropriate safety profile with an investigational new drug application, or IND, and/or NDA-enabling toxicology and clinical trials;

•successfully enrolling in, and completion of, clinical trials;

•receiving marketing approvals from applicable regulatory authorities;

•establishing compliant commercial manufacturing capabilities or making arrangements with third-party manufacturers;

•obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates;

•launching commercial sales of the products, if and when approved, in the United States or in other jurisdictions, whether alone or in collaboration with others, including pursuant to the NewBridge Agreement and Avanzanite Agreement;

•maintaining an acceptable safety profile of the products following approval; and

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•complying with any approval or post-approval requirements.

A change in the outcome of any of these variables with respect to the development of any of our product candidates would significantly change the costs and timing associated with the development of that product candidate.

Research and development expenses consist primarily of costs incurred for our research activities, including our drug discovery efforts, and the development of our product candidates, which include:

•employee-related expenses, including salaries, benefits and stock-based compensation expense;

•expenses incurred under agreements with third parties, including contract research organizations, or CROs, that conduct research and development and both preclinical and clinical activities on our behalf, and the cost of consultants;

•the cost of lab supplies and acquiring, developing and manufacturing preclinical study and clinical trial materials; and

•facilities, depreciation, and other expenses, which include direct and allocated expenses for rent and the maintenance of facilities, insurance and other operating costs.

The following summarizes our products and most advanced programs:

PYRUKYND®/AQVESMETM (mitapivat): First-in-Class PK Activator

We are developing mitapivat for the treatment of PK deficiency and other hemolytic anemias such as thalassemia and SCD. Mitapivat is an orally available small molecule and a potent activator of the wild-type and mutated PK enzymes.

The FDA approved mitapivat, under the brand name PYRUKYND®, for the treatment of hemolytic anemia in adults with PK deficiency in the United States and by the European Commission for the treatment of PK deficiency in adult patients in the EU. Additionally, we received marketing authorization in Great Britain for PYRUKYND® for the treatment of PK deficiency in adult patients under the European Commission Decision Reliance Procedure.

In December 2025, the FDA approved mitapivat under the brand name AQVESMETM for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in the United States. AQVESMETM is the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. We commercially launched AQVESMETM in the United States in late January 2026 following our implementation of a Risk Evaluation and Mitigation Strategy, or REMS, to mitigate the risk of hepatocellular injury. Mitapivat will continue to be marketed as PYRUKYND® in the United States for the PK deficiency indication, which does not require a REMS. The AQVESMETM REMS requires liver tests prior to the first AQVESMETM dose, every four weeks thereafter for 24 weeks, and then as clinically indicated. It also includes education and certification requirements for patients, prescribing physicians, and pharmacists, which are common components of REMS.

In August 2025, we announced that 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 December 2024, we announced that we submitted an MAA to the 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 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-sNDA meeting with the FDA in the first quarter of 2026 and intend to submit a U.S. marketing application for mitapivat in SCD following that engagement.

In addition, we are evaluating mitapivat for the treatment of pediatric patients with PK deficiency. Additionally, mitapivat has received orphan drug designation from the FDA for the treatment of thalassemia and SCD, and orphan medicinal product designation from the EMA for the treatment of SCD. Mitapivat was granted orphan drug designation for the treatment of PK deficiency by the FDA and EMA.

We have full ownership rights to PYRUKYND® and AQVESMETM and expect to fund the future development and commercialization costs related to PYRUKYND® and AQVESMETM. We built our commercial infrastructure to support the commercialization of PYRUKYND® in adult PK deficiency in the United States, and have expanded this infrastructure to support the commercial launch of AQVESMETM in thalassemia in the United States. In July 2024, we entered into a distribution agreement, or the NewBridge Agreement, with NewBridge Pharmaceuticals FZ-LLC, or NewBridge, pursuant to which we granted NewBridge the right to commercialize PYRUKYND® in the GCC region. In June 2025, we entered into a distribution

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agreement, or the Avanzanite Agreement, with Avanzanite Bioscience B.V., or Avanzanite, pursuant to which we granted Avanzanite the right to commercialize PYRUKYND® in the European Economic Area, Switzerland, and the United Kingdom. Under the NewBridge Agreement and the Avanzanite Agreement, we rely on NewBridge and Avanzanite, respectively, to assist with regulatory filings, prepare applications for pricing and reimbursement approval, negotiate with payors, conduct medical affairs activities and import, distribute, promote and commercialize our products in accordance with applicable law in the applicable jurisdictions.

In connection with our regulatory approvals in the EU, Great Britain and Saudi Arabia, we provide access to PYRUKYND® to eligible patients through the Avanzanite Agreement and the NewBridge Agreement, as applicable, and on either a free of charge or for charge basis for eligible patients in those jurisdictions and other jurisdictions through a global managed access program. Revenues associated with the NewBridge Agreement, the Avanzanite Agreement and the for charge portion of our global managed access program are included in the rest of world product revenue line within Results of Operations. We continue to evaluate other options for the commercialization of PYRUKYND® outside of the United States, including through exploring potential partnership opportunities.

We are evaluating mitapivat in numerous clinical trials, including the following:

•An extension study evaluating the long-term safety, tolerability and efficacy of treatment with mitapivat in SCD patients who are 16 years of age or older from RISE UP, our completed double-blind phase 3 study evaluating the efficacy and safety of mitapivat as a potential treatment for SCD.

RISE UP, a phase 2/3 study evaluating the efficacy and safety of mitapivat in SCD patients who are 16 years of age or older, have had between two and 10 sickle cell pain crises, or SCPCs, in the past 12 months, and have hemoglobin within the range of 5.5 to 10.5 g/dL during screening. We enrolled 207 patients in the phase 3 portion of the trial, which included a 52-week double blind, randomized, placebo-controlled period in which participants were randomized in a 2:1 ratio to receive the recommended (100 mg twice daily) mitapivat dose level or the placebo. The 52-week double-blind treatment period was completed by 87.0% (n=120/138) of patients in the mitapivat arm and 81.2% (n=56/69) of patients in the placebo arm. All but two of these patients (174/176) opted to enter the ongoing 216-week open-label extension period of the study. The primary endpoints of the phase 3 portion of the trial were (i) hemoglobin response, defined as ≥1 g/dL increase in average hemoglobin from week 24 through week 52 compared to baseline, and (ii) annualized rate of SCPCs. The secondary endpoints included change from baseline in hemoglobin concentration, change from baseline in indirect bilirubin, change from baseline in Patient Reported Outcome Measurement Information System Fatigue 13a, or PROMIS Fatigue, Short Form scores, annualized frequency of hospitalizations for SCPCs, and change from baseline in percent reticulocyte levels. In November 2025, we announced that the phase 3 portion of the trial had achieved the primary endpoint of hemoglobin response in the mitapivat arm, with 40.6% of patients in the mitapivat arm having achieved a hemoglobin response, compared to 2.9% of patients in the placebo arm, a statistically significant improvement (2-sided p<0.0001). In patients who achieved a hemoglobin response in the mitapivat arm, mean change from baseline in average hemoglobin concentration from Week 24 through Week 52 was 1.6 g/dL. The annualized rate of SCPCs, defined as acute pain needing medical contact, acute chest syndrome, priapism, hepatic, or splenic sequestration, was 2.62 in the mitapivat arm and 3.05 in the placebo arm (2-sided p=0.1213), with such reduction of SCPCs not achieving statistical significance for that primary endpoint. Treatment with mitapivat also showed statistically significant improvements in two secondary endpoints: (a) the average change from baseline in hemoglobin concentration from Week 24 through Week 52 was 7.69 g/L in the mitapivat arm and 0.26 g/L in the placebo arm, a statistically significant improvement (2-sided p<0.0001), and (b) the average change from baseline in indirect bilirubin from Week 24 through Week 52 was -16.03 μmol/L in the mitapivat arm and 0.88 μmol/L in the placebo arm, a statistically significant improvement (2-sided p<0.0001). The average change from baseline in PROMIS Fatigue score from Week 24 through Week 52 was -2.72 in the mitapivat arm and -2.25 in the placebo arm (2-sided p=0.7112), indicating improvements in fatigue, but the PROMIS Fatigue secondary endpoint was not met. No conclusions could be drawn regarding the statistical significance of the following additional key secondary endpoints: (a) the annualized frequency of hospitalizations for SCPCs, with 1.56 in the mitapivat arm and 1.81 in the placebo arm (2-sided nominal p=0.2498), and (b) the average change from baseline in percent reticulocyte levels from Week 24 through Week 52, with -0.0236 (fraction of 1) in the mitapivat arm and -0.0013 (fraction of 1) in the placebo arm (2-sided nominal p=0.0001). We also announced that in the subset of patients in the mitapivat arm achieving the primary endpoint of hemoglobin response, the following was observed: (i) the annualized rate of SCPCs was 2.20 for hemoglobin responders and 2.98 for non-hemoglobin responders (rate ratio [RR]=0.74, 95% confidence interval [CI]=0.58 to 0.94); (ii) the annualized frequency of hospitalizations for SCPCs was 1.16 for hemoglobin responders and 1.76 for non-hemoglobin responders (RR=0.66, 95% CI=0.48 to 0.91); and (iii) the average change in PROMIS Fatigue score between Week 24 and Week 52 was -5.19 for hemoglobin responders and -2.55 for non-hemoglobin responders (95% CI=-5.59 to 0.32). The results for hemoglobin responders in the mitapivat arm exceeded -4.1, the threshold for a clinically meaningful change from baseline for PROMIS Fatigue score. The safety profile for mitapivat observed in the phase 3 portion of the trial was generally consistent with that observed in prior mitapivat SCD trials. We observed as follows: (i) a similar proportion of

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patients on mitapivat (n=134, 97.1%) and placebo (n=68, 98.6%) had adverse events; (ii) serious TEAEs were reported in 20.3% (n=28) and 29.0% (n=20) of patients on mitapivat and placebo, respectively; 0.7% (n=1) and 0.0% (n=0), respectively, were considered treatment-related; (iii) liver abnormalities observed across the mitapivat and placebo arms were not suggestive of drug-induced hepatocellular injury, unlike what was observed in the mitapivat ENERGIZE and ENERGIZE-T phase 3 trials; (iv) TEAEs led to treatment discontinuation in 4.3% (n=6) of patients on mitapivat and 2.9% (n=2) on placebo; and (v) three deaths (2.2%) occurred in patients on mitapivat, and two (2.9%) on placebo, none of which were deemed related to study treatment by the trial investigator.

•Extension studies evaluating the long-term safety, tolerability and efficacy of treatment with mitapivat in pediatric patients from ACTIVATE-kids and ACTIVATE-kidsT, our completed double-blind phase 3 studies evaluating the efficacy and safety of mitapivat as a potential treatment for PK deficiency in not regularly transfused and regularly transfused patients between one and 18 years old, respectively.

We announced topline data for ACTIVATE-kidsT in August 2024. A total of 49 patients were enrolled in ACTIVATE-kidsT, with 32 randomized to mitapivat twice-daily and 17 randomized to matched placebo. 30 patients (93.8%) in the mitapivat arm and 16 (94.1%) in the placebo arm completed the 32-week double-blind period of the study. The primary endpoint of ACTIVATE-kidsT is transfusion reduction response, defined as ≥33% reduction in total RBC transfusion volume from week 9 through week 32 of the double-blind period. Using Bayesian methodology, the prespecified statistical criterion for the primary endpoint in ACTIVATE-kidsT was not met using low or moderate borrowing of data from the ACTIVATE-T study in adults. In the study, 28.1% of patients in the mitapivat arm achieved the primary endpoint of transfusion reduction response, compared to 11.8% of patients in the placebo arm. Transfusion-free response and normal hemoglobin response were secondary endpoints in this study and only observed in patients in the mitapivat arm. In the 32-week double-blind treatment period, mitapivat was generally safe and well-tolerated, with safety results consistent with the safety profile for mitapivat previously observed in adults with PK deficiency who are regularly transfused.

We announced topline data for ACTIVATE-kids in February 2025. A total of 30 patients were enrolled in ACTIVATE-kids, with 19 randomized to mitapivat twice-daily and 11 randomized to matched placebo. All patients in both treatment arms completed the 20-week double-blind period of the study. The primary endpoint of ACTIVATE-kids is percentage of patients with hemoglobin response, defined as ≥1.5 g/dL increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at weeks 12, 16, and 20 during the double-blind period. Using Bayesian methodology, the prespecified statistical criterion for the primary endpoint in ACTIVATE-kids was met using a range of relative borrowing from the adult ACTIVATE study, for all possible borrowing weights (ranging from 0 to 1). In addition, the pre-specified supportive analysis based on traditional methodology comparing the hemoglobin response rate for mitapivat versus placebo provided further evidence that the primary endpoint was met. There were 31.6% of patients in the mitapivat arm achieving a hemoglobin response compared to 0% of patients in the placebo arm; the 95% confidence interval for the difference in hemoglobin response rates between mitapivat and placebo was >0 (95% CI=10.8% to 52.7%). In addition, improvements in changes from baseline for markers of hemolysis (indirect bilirubin, lactate dehydrogenase and haptoglobin) were observed in the mitapivat arm compared to the placebo arm. In the 20-week double-blind period of the study, a similar proportion of patients had AEs in the mitapivat and placebo arms and there were no discontinuations of study treatment due to AEs or for any reason. The safety results from the trial were consistent with the safety profile for mitapivat previously observed for adult patients with PK deficiency who are not regularly transfused.

•An extension study evaluating the long-term safety, tolerability and efficacy of treatment with mitapivat in patients from ACTIVATE and ACTIVATE-T, our completed pivotal trials of mitapivat in not regularly transfused and regularly transfused adult patients with PK deficiency.

•An extension study evaluating the long-term safety, tolerability and efficacy of treatment with mitapivat in patients from DRIVE PK, our completed global phase 2, first-in-patient, open-label safety and efficacy clinical trial of mitapivat in adult, not regularly transfused patients with PK deficiency.

•An extension study evaluating the long-term efficacy and safety of treatment with mitapivat in patients from ENERGIZE and ENERGIZE-T, our completed pivotal trials of mitapivat in adults with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.

During the double-blind periods of ENERGIZE and ENERGIZE-T, two patients on mitapivat experienced events of hepatocellular injury. In addition, during the open-label extension periods of both trials, a total of three patients experienced events of hepatocellular injury after switching from placebo to mitapivat. All of these events occurred within the first six months of exposure to mitapivat and liver tests improved following discontinuation of mitapivat. Based on the results of the ENERGIZE and ENERGIZE-T trials, we included in our regulatory applications hepatocellular injury as an important potential risk of mitapivat in patients with thalassemia and proposed monthly monitoring of liver tests for the first six months of

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treatment with mitapivat. We updated our mitapivat clinical trial protocols across all indications to incorporate monthly monitoring of liver tests for the first six months of treatment.

Tebapivat: Novel PK Activator

We are developing tebapivat, a novel PK activator for the potential treatment of LR MDS and SCD. Tebapivat has been granted orphan drug designation for the treatment of MDS by the FDA.

We have completed a phase 1 clinical trial evaluating tebapivat in healthy volunteers and patients with SCD, and we have completed enrollment in the phase 2 clinical trial of tebapivat in adult patients with SCD. We expect to announce topline data for this trial in the second half of 2026.

We also initiated a phase 2a clinical trial of tebapivat in adults with LR MDS in the third quarter of 2022, and the trial has completed enrollment with 22 patients, including 12 patients classified as non-transfused and 10 patients classified as low transfusion burden. Patients received 5 mg of tebapivat once daily for up to 16 weeks. The two primary endpoints of the trial were transfusion independence (for patients classified as low transfusion burden), defined as transfusion-free for ≥ eight consecutive weeks during the 16-week treatment period, and hemoglobin response, defined as a ≥ 1.5 g/dL increase from baseline in the average hemoglobin concentration measured from week 8 through week 16.

In November 2023, we announced that we achieved clinical proof-of-concept in the phase 2a portion of the trial. We observed that four of the 10 patients with low transfusion burden achieved the transfusion independence endpoint, and one of the 22 patients achieved the hemoglobin response endpoint in the 16-week treatment period. The safety profile observed was consistent with data reported in the healthy volunteer study of tebapivat. 19 patients elected to enroll in the extension period of the trial for up to 156 weeks. We evaluated the phase 2a trial results and assessed the impact of those results on the phase 2b portion of the protocol, and based on the data generated in the phase 2a portion of the trial, we increased the dosage levels evaluated in the phase 2b portion of the trial, which we initiated in the third quarter of 2024. We completed enrollment in the phase 2b portion of the trial in September 2025 and expect to announce topline data for this trial in the first half of 2026.

Other Programs

In addition to the aforementioned development programs, we are developing AG-181, a PAH stabilizer for the potential treatment of PKU, for which we filed an investigational new drug application, or IND, in December 2023. We initiated a phase 1 clinical trial of AG-181 in healthy volunteers in the first quarter of 2024, initiated the multiple ascending dose portion of the trial in the second quarter of 2025, and completed the trial in December 2025. We expect to initiate a phase 1b proof of mechanism trial of AG-181 in patients with PKU in the first half of 2026 and confirm proof of mechanism in the second half of 2026.

Also, in July 2023, we entered into a license agreement with Alnylam for the development and commercialization of products containing or comprised of an siRNA preclinical development candidate discovered by Alnylam and targeting the TMPRSS6 gene, and we are developing a product candidate, AG-236, for the potential treatment of patients with PV. We filed an IND with the FDA for AG-236 for the treatment of PV, which cleared in June 2025, and we initiated a phase 1 clinical trial evaluatingAG-236 in healthy volunteers in July 2025. We expect to announce topline data for this trial in the first half of 2026.

Selling, General and Administrative Expenses

Selling, general and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in executive, finance, business development, commercial, legal, information technology and human resources functions. Other significant costs include facility-related costs not otherwise included in research and development expenses, legal fees relating to patent and corporate matters, and fees for accounting and consulting services.

We anticipate that our selling, general and administrative expenses will increase in the future to support continued research and development activities, and ongoing and future commercialization activities related to our portfolio, including the ongoing commercialization of PYRUKYND®, AQVESMETM and any of our other product candidates, which may include the hiring of additional personnel.

Critical Accounting Policies and Significant Judgments and Estimates

Our management’s discussion and analysis of our financial condition and results of operations are based on our consolidated financial statements, which we have prepared in accordance with accounting principles generally accepted in the United States. The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported amounts of revenue and expenses during the reporting periods. On an ongoing basis, we evaluate our estimates and judgments. We base our estimates on historical experience and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of

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assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.

While our significant accounting policies are described in more detail in the notes to our consolidated financial statements included in this Annual Report on Form 10-K, we believe that the following accounting policies are the most critical in fully understanding and evaluating our financial condition and results of operations and are policies that require a significant level of judgment and estimates.

Revenue recognition

Under ASC 606, Revenue from Contracts with Customers, or ASC 606, revenue is recognized when the customer obtains control of promised goods or services, in an amount that reflects the consideration that we expect to receive in exchange for those goods or services. To determine revenue recognition for arrangements that have been determined to be within the scope of ASC 606, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when it is probable that we will collect the consideration we are entitled to in exchange for the goods or services we transfer to the customer.

This standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments.

Once the contract is determined to be within the scope of ASC 606, we assess the goods or services promised within each contract and determine those that are performance obligations, and assess whether each promised good or service is distinct. We will then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied.

Product Revenue

We generate product revenue from sales of PYRUKYND® in the United States to a limited number of specialty distributors and specialty pharmacy providers, and to Avanzanite and NewBridge outside of the United States, 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 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®.

The performance obligation related to the sale of PYRUKYND® is satisfied and revenue is recognized when the Customer obtains control of the product, which occurs at a point in time, typically upon delivery to the Customer.

Revenues from product sales are recorded at the net sales price, or transaction price, which includes estimates of variable consideration for which reserves are established and result from contractual adjustments, government rebates, returns and other allowances that are offered within the contracts with our Customers, healthcare providers, payors and other indirect customers relating to the sale of our products.

Contractual Adjustments. We generally provide Customers with discounts, including prompt pay discounts, and allowances that are explicitly stated in the contracts and are recorded as a reduction of revenue in the period the related product revenue is recognized. In addition, we receive sales order management, data and distribution services from certain Customers.

Chargebacks and discounts represent the estimated obligations resulting from contractual commitments to sell products to qualified healthcare providers at prices lower than the list prices charged to Customers who directly purchase the product from us. Customers charge us for the difference between what they pay for the product and the ultimate selling price to the qualified healthcare providers. These reserves are estimated using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated channel mix and are established in the same period that the related revenue is recognized, resulting in a reduction of product revenue.

Government Rebates. Government rebates include Medicare, TriCare, and Medicaid rebates, which we estimate using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated payor mix. These reserves are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue.

Returns. We estimate the amount of product sales that may be returned by Customers and record this estimate as a reduction of revenue in the period the related product revenue is recognized. We currently estimate product return liabilities using the expected value method, based on available industry data, including our visibility into the inventory remaining in the distribution channel.

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Accrued Research and Development Expenses

As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued expenses. This process involves reviewing quotations and contracts, identifying services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost. Certain service providers invoice us in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in our financial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers and make adjustments, if necessary. Examples of estimated accrued research and development expenses include fees paid to: (i) CROs and other third parties in connection with clinical trials and preclinical development activities; (ii) investigative sites in connection with clinical trials; and (iii) third parties related to product manufacturing, development and distribution of clinical supplies.

We base our expenses related to CROs on our estimates of the services received and efforts expended pursuant to quotes and contracts with CROs that conduct research and development on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the research and development expense. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid accordingly. Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and could result in us reporting amounts that are too high or too low in any particular period.

Stock-based Compensation

Expected term. We use the “simplified method” as prescribed by the SEC Staff Accounting Bulletin No. 107, Share Based Payments, to estimate the expected term of stock option grants. Under this approach, the weighted-average expected life is presumed to be the average of the contractual term of ten years and the weighted-average vesting term of the stock options, taking into consideration multiple vesting tranches. We utilize this method due to the plain-vanilla nature of our share-based awards.

Volatility. The expected volatility has been determined using our historical volatilities for a period equal to the expected term of the option grant.

Risk-free rate. The risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the options being valued.

Dividends. We have never paid, and do not anticipate paying, any cash dividends in the foreseeable future, and, therefore, use an expected dividend yield of zero in the option-pricing model.

Forfeitures. We account for forfeitures as they occur and, therefore, do not estimate forfeitures.

For awards subject to service-based vesting conditions, we recognize stock-based compensation expense equal to the grant date fair value of stock options on a straight-line basis over the requisite service period. For awards subject to performance-based vesting conditions, we recognize stock-based compensation expense if the performance condition is considered probable of achievement using management’s best estimates.

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Results of Operations

Comparison of years ended December 31, 2025, 2024 and 2023

Revenues

Revenues:

Product revenue, net

Total Revenue – 2025 vs. 2024 – The increase in total revenue of $17.5 million in 2025 compared to 2024 was due to an increase of $12.8 million in U.S. product revenue and an increase of $4.7 million in rest of world product revenue. The increase in U.S. product revenue was primarily due to increased volume associated with PYRUKYND®, and the increase in rest of world product revenue was primarily due to increased volume associated with the Avanzanite Agreement discussed above in Overview.

Total Revenue – 2024 vs. 2023 – The increase in total revenue of $9.7 million in 2024 compared to 2023 was primarily due to increased U.S. product revenue as a result of increased volume associated with PYRUKYND®.

Total Operating Expenses

Operating expenses

Total Operating Expenses – 2025 vs. 2024 – The increase in total operating expenses of $63.9 million in 2025 compared to 2024 was primarily due to an increase of $38.2 million in research and development expenses, which is described below under Research and Development Expenses, and an increase of $23.5 million in selling, general and administrative expenses, driven by an increase in commercial-related activities as we prepared for the approval of AQVESMETM in thalassemia, which was approved by the FDA on December 23, 2025.

Total Operating Expenses – 2024 vs 2023 – The increase in total operating expenses of $43.9 million in 2024 compared to 2023 was primarily due to an increase of $36.9 million in selling, general and administrative expenses, driven by an increase in commercial-related activities as we prepared for the potential approval of PYRUKYND® in thalassemia, and an increase of $5.8 million in research and development expenses, which is described below under Research and Development Expenses.

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Research and Development Expenses

Our research and development expenses, by major program, are outlined in the table below:

In-process research and development 10,000 — 17,500

Total Research and Development Expenses – 2025 vs. 2024 – The increase in research and development expenses of $38.2 million in 2025 compared to 2024 was due to a $28.0 million increase in our direct expenses and a $10.2 million increase in our indirect expenses. The increase in direct expenses was primarily due to an increase of $17.1 millionin tebapivat costs, driven by increased costs associated with clinical trials of tebapivat in patients with SCD and LR MDS and higher process development expenses, and an increase in in-process research and development as a result of the $10.0 million milestone payment associated with the agreement with Alnylam discussed above under Overview. The increase in indirect expenses was primarily due to a $7.0 million increase in compensation and related expenses due to an increase in workforce related expenses.

Total Research and Development Expenses – 2024 vs 2023 – The increase in research and development expenses of $5.8 million in 2024 compared to 2023 was due to a $6.3 million increase in our indirect expenses, partially offset by a $0.6 million decrease in our direct expenses. The increase in indirect expenses was primarily due to a $6.1 million increase in compensation and related expenses due to an increase in workforce related expenses. The decrease in direct expenses was due to the $17.5 million up-front payment in 2023 associated with the Alnylam license agreement discussed above under Overview and a decrease of $3.7 millionin tebapivat costs due to decreased costs associated with clinical trials of tebapivat in patients with SCD and LR MDS, offset by an $11.4 million increase in PYRUKYND® costs and a $9.3 million increase in AG-236, the in-licensed siRNA TMPRSS6 program for PV, primarily driven by higher process development expenses. The increase in PYRUKYND® costs was primarily due to increased process development expenses and increased costs associated with clinical trials for patients with SCD, partially offset by lower costs associated with the phase 3 clinical trials of PYRUKYND® in patients with thalassemia, ENERGIZE and ENERGIZE-T.

Other Income and Expense

Gain on sale of contingent payments $ — $ 889,136 $ —

Milestone payment from gain on sale of oncology business — 200,000 —

Other Income and Expense – 2025 vs. 2024 – The decrease in gain on sale of contingent payments in 2025 compared to 2024 was due to the sale of the Vorasidenib Royalty Rights in 2024 discussed above in Overview. The decrease in milestone payment from gain on sale of oncology business was due to the receipt of the Vorasidenib Milestone Payment in 2024 as discussed above in Overview. The $8.3 million increase in interest income, net in 2025 compared to 2024 is primarily attributable to increased return on our investments.

Other Income and Expense – 2024 vs 2023 – The increase in gain on sale of contingent payments in 2024 compared to 2023 was due to the sale of the Vorasidenib Royalty Rights in 2024 discussed above in Overview. The increase in milestone payment from gain on sale of oncology business was due to the receipt of the Vorasidenib Milestone Payment in 2024 as discussed above in Overview. The $14.7 million increase in interest income, net in 2024 compared to 2023 is primarily attributable to increased return on our investments.

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Net (Loss) Income

Net (Loss) Income – 2025 vs 2024 – The change in net (loss) income in 2025 compared to 2024 was primarily driven by the sale of the Vorasidenib Royalty Rights in 2024 discussed above in Overview and the receipt of the Vorasidenib Milestone Payment in 2024 discussed above in Overview, partially offset by the decrease in income tax expense as a result of the income related to the sale of the Vorasidenib Royalty Rights and the receipt of the Vorasidenib Milestone Payment in 2024.

Net (Loss) Income – 2024 vs 2023 – The increase in net income in 2024 compared to 2023 was primarily driven by the sale of the Vorasidenib Royalty Rights in 2024 discussed above in Overview and the receipt of the Vorasidenib Milestone Payment in 2024 discussed above in Overview, partially offset by the increase in income tax expense as a result of the income related to the sale of the Vorasidenib Royalty Rights and the receipt of the Vorasidenib Milestone Payment.

Liquidity and Capital Resources

Sources of Liquidity

Since our inception, and 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 AQVESMETM 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.

On March 31, 2021, we completed the sale of our oncology business to 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 the right to the Vorasidenib Milestone Payment and the Vorasidenib Royalty Rights. The Vorasidenib Milestone Payment and Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.

Our cash, cash equivalents and marketable securities balance was $1.2 billion at December 31, 2025. The Retained Earn-Out Rights discussed above are our only committed potential external sources of funds. We cannot predict what success, if any, Servier may have in the United States with respect to the sale of vorasidenib, and consequently, we cannot estimate the amount of payments, if any, we may receive on account of the Retained Earn-Out Rights.

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Cash Flows

The following table provides information regarding our cash flows for the years ended December 31, 2025, 2024 and 2023:

Net cash used in operating activities

Cash used in operating activities of $373.0 million during the year ended December 31, 2025 was primarily due to operating expenses driven by research and development costs described above under Research and Development Expenses, partially offset by cash received related to interest income of $59.0 million and cash received from product revenues of $50.5 million.

Cash used in operating activities of $389.8 million during the year ended December 31, 2024 was primarily due to operating expenses driven by research and development costs described above under Research and Development Expenses, partially offset by cash received related to interest income of $43.5 million and cash received from product revenues of $37.8 million.

Cash used in operating activities of $296.1 million during the year ended December 31, 2023 was primarily due to operating expenses driven by research and development costs described above under Research and Development Expenses, partially offset by cash received related to interest income of $31.2 million and cash received from revenues of $28.6 million.

Net cash provided by investing activities

Cash provided by investing activities of $377.2 million during the year ended December 31, 2025 was primarily due to higher proceeds from maturities and sales of marketable securities than purchases of marketable securities.

Cash provided by investing activities of $363.4 million during the year ended December 31, 2024 was primarily due to the proceeds from the Upfront Payment from Royalty Pharma and the Vorasidenib Milestone Payment from Servier, partially offset by higher purchases of marketable securities than proceeds from maturities and sales of marketable securities as a result of the proceeds from the Upfront Payment and the Vorasidenib Milestone Payment.

Cash provided by investing activities for the year ended December 31, 2023 was primarily due to higher proceeds from maturities and sales of marketable securities than purchases of marketable securities, partially offset by the $17.5 million up-front payment associated with the Alnylam license agreement discussed above under Overview.

Net cash provided by financing activities

Cash provided by financing activities for the year ended December 31, 2025 was due to $8.7 million of proceeds received from stock option exercises and purchases made pursuant to our employee stock purchase plan.

Cash provided by financing activities for the year ended December 31, 2024 was due to $14.4 million of proceeds received from stock option exercises and purchases made pursuant to our employee stock purchase plan.

Cash provided by financing activities for the year ended December 31, 2023 was due to $5.4 million of proceeds received from stock option exercises and purchases made pursuant to our employee stock purchase plan.

Funding Requirements

We expect our expenses to increase as we continue the research, development and clinical trials of, seek marketing approvals for, and commercialize our product candidates in our portfolio, including as we continue to commercialize PYRUKYND® and AQVESMETM for their approved indications. If we obtain additional marketing approvals for mitapivat in sickle cell disease or in other indications, or for any of our other product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution.

We expect that our existing cash, cash equivalents and marketable securities as of December 31, 2025, together with anticipated product revenue and interest income, will provide the financial independence to commercially launch AQVESMETM in the United States, prepare for the potential U.S. commercial launch of mitapivat in SCD, advance our existing clinical programs, and opportunistically expand our pipeline through both internally and externally discovered assets. Our expectations regarding

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our long-term funding requirements are based on assumptions that may prove to be wrong, and we may need additional capital resources to fund our operating plans and capital expenditure requirements.

Our future capital requirements will depend on many factors, including:

•the amount and timing of future revenue received from commercial sales of PYRUKYND®, AQVESMETM or any of our other product candidates for which we may receive marketing approval;

•the amount of payments, if any, we may receive on account of the Retained Earn-Out Rights;

•the costs and timing of our ongoing and future commercialization activities, including product manufacturing, sales, marketing and distribution for PYRUKYND® and AQVESMETM in the approved jurisdictions and indications and for any product candidate for which we may receive approval;

•the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our product candidates;

•the costs associated with in-licensing or acquiring assets for pipeline growth, including the amount and timing of future milestone and royalty payments potentially payable to Alnylam pursuant to the license agreement;

•the costs, timing and outcome of regulatory review of our product candidates;

•the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;

•our ability to establish and maintain collaborations on favorable terms, if at all;

•our ability to successfully execute on our strategic plans;

•operational delays due to public health epidemics; and

•operational delays, disruptions and/or increased costs associated with global economic and political developments.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs 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 AQVESMETM 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. We do not have any committed external source of funds other than the Retained Earn-Out Rights. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, selling or licensing our assets, making capital expenditures or declaring dividends.

If we raise funds through collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates, or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed or on attractive terms, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Off-Balance Sheet Arrangements

We did not have, during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under applicable SEC rules.

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Contractual Obligations

The following table summarizes our significant contractual obligations as of the payment due date by period at December 31, 2025:

Payments due by period

(In thousands) Total Lessthan1 year 1-3years 3-5years Morethan5 years

(1) Relates to payment obligations under lease agreements covering approximately 146,000 square feet at 88 Sidney Street, 43,000 square feet at 64 Sidney Street, and 13,000 square feet at 38 Sidney Street, Cambridge, Massachusetts. All leases, as amended, expire on February 29, 2028. At the end of the initial lease period, we have the option to extend the leases at all facilities for two consecutive five-year periods at the fair market rent at the time of the extension.

(2) Relates to payment obligations under a packaging and supply agreement for drug product.

(3) Relates to payment obligations under a development and manufacturing services agreement for drug product. Arrangement is for a remaining contractual term of four years, however, the total funds can be allocated in any manner to meet the agreement terms.

We also enter into agreements in the normal course of business with CROs for clinical trials and contract manufacturing organizations, or CMOs, for supply manufacturing, and with vendors for preclinical research studies and other services and products for operating purposes. These contractual obligations are cancelable at any time by us, generally upon prior written notice to the vendor, and are thus not included in the contractual obligations table.

In July 2023, we entered into a license agreement with Alnylam as discussed above under Overview and under Note 1, Nature of Business, to our consolidated financial statements. Under the license agreement, we may be required to pay up to an additional $120.0 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. Such payment obligations are contingent upon the occurrence of future events and the timing and likelihood of such potential obligations are not known.

Item 7A. Quantitative and Qualitative Disclosures about Market Risk

We are exposed to market risk related to changes in interest rates. As of December 31, 2025 and December 31, 2024, we had cash, cash equivalents and marketable securities of $1.2 billion and $1.5 billion, respectively, consisting primarily of investments in U.S. Treasuries, government securities, corporate debt securities and certificates of deposit. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our investments are primarily in short-term marketable securities. Our marketable securities are subject to interest rate risk and could fall in value if market interest rates increase. Due to the short-term duration of our investment portfolio and the low risk profile of our investments, we do not believe an immediate and uniform 100 basis point change in interest rates would have a material effect on the fair market value of our investment portfolio.

We are also exposed to market risk related to changes in foreign currency exchange rates. We have contracts with CROs and CMOs that are located in Asia and Europe and are denominated in foreign currencies. We are subject to fluctuations in foreign currency rates in connection with these agreements. We do not currently hedge our foreign currency exchange rate risk. As of December 31, 2025 and December 31, 2024, we had minimal or no liabilities denominated in foreign currencies.

Item 8. Financial Statements and Supplementary Data

The financial statements required to be filed pursuant to this Item 8 are appended to this Annual Report on Form 10-K. An index of those financial statements is found in Item 15, Exhibits and Financial Statement Schedules, of this Annual Report on Form 10-K.

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

None.

Item 9A. Controls and Procedures

Evaluation of Disclosure Controls and Procedures

Our management, with the participation of our principal executive officer and our principal financial officer, evaluated, as of the end of the period covered by this Annual Report on Form 10-K, the effectiveness of our disclosure controls and procedures.

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Based on that evaluation of our disclosure controls and procedures as of December 31, 2025, our principal executive officer and principal financial officer concluded that our disclosure controls and procedures as of such date are effective at the reasonable assurance level. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act are recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports we file or submit under the Exchange Act is accumulated and communicated to our management, including our principal executive officer and principal financial officer, as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and our management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures.

Management’s Annual Report on Internal Control over Financial Reporting

Our management is responsible for establishing and maintaining adequate internal control over our financial reporting. Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) promulgated under the Exchange Act as a process designed by, or under the supervision of, our principal executive and principal financial officers and effected by our board of directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with U.S. GAAP. Our internal control over financial reporting includes those policies and procedures that:

•pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect our transactions and dispositions of our assets;

•provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with U.S. GAAP, and that our receipts and expenditures are being made only in accordance with authorizations of our management and directors; and

•provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of our assets that could have a material effect on our financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

Our management assessed the effectiveness of our internal control over financial reporting as of December 31, 2025. In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in its 2013 Internal Control – Integrated Framework. Based on our assessment, our management has concluded that, as of December 31, 2025, our internal control over financial reporting is effective based on those criteria.

The effectiveness of our internal control over financial reporting as of December 31, 2025, has been audited by PricewaterhouseCoopers LLP, an independent registered public accounting firm, as stated in their report, which is included herein.

Changes in Internal Control over Financial Reporting

There were no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) during the fiscal quarter ended December 31, 2025 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

Item 9B. Other Information

(b) Director and Officer Trading Arrangements

A significant portion of the compensation of our directors and officers (as defined in Rule 16a-1(f) under the Exchange Act) is in the form of equity awards and, from time to time, directors and officers engage in open-market transactions with respect to the securities acquired pursuant to such equity awards or other of our securities, including to satisfy tax withholding obligations when equity awards vest or are exercised, and for diversification or other personal reasons.

Transactions in our securities by directors and officers are required to be made in accordance with our insider trading policy, which requires that the transactions be in accordance with applicable U.S. federal securities laws that prohibit trading while in possession of material nonpublic information. Rule 10b5-1 under the Exchange Act provides an affirmative defense that enables directors and officers to prearrange transactions in our securities in a manner that avoids concerns about initiating transactions while in possession of material nonpublic information.

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Each Rule 10b5-1 trading arrangement described below was entered into in accordance with our insider trading policy, and only permitted or permits transactions upon the expiration of the applicable mandatory cooling-off periods under Rule 10b5-1 of the Exchange Act. Actual transactions are required to be disclosed publicly in Section 16 filings with the SEC.

The following table describes, for the fourth quarter of 2025, each trading arrangement for the sale or purchase of Company securities adopted or terminated by our directors and officers that is either (1) a contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) (a “Rule 10b5-1 trading arrangement”) or (2) a “non-Rule 10b5-1 trading arrangement” (as defined in Item 408(c) of Regulation S-K):

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections

Not applicable.

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PART III

Item 10. Directors, Executive Officers and Corporate Governance

The information required by this Item 10 will be included in our definitive proxy statement to be filed with the Securities and Exchange Commission, or SEC, with respect to our 2026 Annual Meeting of Stockholders and is incorporated herein by reference.

Item 11. Executive Compensation

The information required by this Item 11 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2026 Annual Meeting of Stockholders and, other than the information required by Item 402(v) of Regulation S-K, is incorporated herein by reference.

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

The information required by this Item 12 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2026 Annual Meeting of Stockholders and is incorporated herein by reference.

Item 13. Certain Relationships and Related Transactions, and Director Independence

The information required by this Item 13 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2026 Annual Meeting of Stockholders and is incorporated herein by reference.

Item 14. Principal Accountant Fees and Services

The information required by this Item 14 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2026 Annual Meeting of Stockholders and is incorporated herein by reference.

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PART IV

Item 15. Exhibits and Financial Statement Schedules

(1) Financial Statements

The following documents are included on pages F-1 through F-28 attached hereto and are filed as part of this Annual Report on Form 10-K.

Report of Independent Registered Public Accounting Firm (PCAOB ID 238) F-2

Consolidated Balance Sheets F-4

Consolidated Statements of Operations F-5

Consolidated Statements of Comprehensive (Loss) Income F-6

Consolidated Statements of Stockholders’ Equity F-7

Consolidated Statements of Cash Flows F-8

Notes to Consolidated Financial Statements F-9

(2) Financial Statement Schedules

Schedules have been omitted since they are either not required or not applicable or the information is otherwise included herein.

(3) Exhibits

ExhibitNumber Description of Exhibit Incorporated by Reference FiledHerewith

Form FileNumber Date of Filing ExhibitNumber

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21.1 Subsidiaries of the Registrant X

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101.INS XBRL Instance Document X

101.SCH XBRL Taxonomy Extension Schema Document X

101.CAL XBRL Taxonomy Calculation Linkbase Document X

101.DEF XBRL Taxonomy Extension Definition Linkbase Document X

101.LAB XBRL Taxonomy Label Linkbase Document X

101.PRE XBRL Taxonomy Presentation Linkbase Document X

# Indicates management contract or compensatory plan or arrangement.

Item 16. Form 10-K Summary

None.

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SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

AGIOS PHARMACEUTICALS, INC.

February 12, 2026 By: /s/ Brian Goff

Brian GoffChief Executive Officer

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated.

Signature Title Date

Brian Goff

Cecilia Jones

T.J. Washburn

/s/ Jacqualyn A. Fouse Chair of the Board of Directors February 12, 2026

Jacqualyn A. Fouse, Ph.D.

/s/ Jay Backstrom Director February 12, 2026

Jay Backstrom, M.D., M.P.H.

/s/ Rahul Ballal Director February 12, 2026

Rahul Ballal, Ph.D.

/s/ Jeffrey Capello Director February 12, 2026

Jeffrey Capello

/s/ Kaye Foster Director February 12, 2026

Kaye Foster

/s/ Maykin Ho Director February 12, 2026

Maykin Ho, Ph.D.

/s/ Catherine Owen Adams Director February 12, 2026

Catherine Owen Adams

/s/ David Scadden Director February 12, 2026

David Scadden, M.D.

/s/ Cynthia Smith Director February 12, 2026

Cynthia Smith

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Agios Pharmaceuticals, Inc.

Index to Consolidated Financial Statements

Report of Independent Registered Public Accounting Firm (PCAOB ID 238) F-2

Consolidated Balance Sheets F-4

Consolidated Statements of Operations F-5

Consolidated Statements of Comprehensive (Loss) Income F-6

Consolidated Statements of Stockholders’ Equity F-7

Consolidated Statements of Cash Flows F-8

Notes to Consolidated Financial Statements F-9

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Report of Independent Registered Public Accounting Firm

To the Board of Directors and Stockholders of Agios Pharmaceuticals, Inc.

Opinions on the Financial Statements and Internal Control over Financial Reporting

We have audited the accompanying consolidated balance sheets of Agios Pharmaceuticals, Inc. and its subsidiaries (the “Company”) as of December 31, 2025 and 2024, and the related consolidated statements of operations, of comprehensive (loss) income, of stockholders’ equity and of cash flows for each of the three years in the period ended December 31, 2025, including the related notes (collectively referred to as the “consolidated financial statements”).We also have audited the Company's internal control over financial reporting as of December 31, 2025, based on criteria established in Internal Control - Integrated Framework(2013)issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO).

In our opinion, the consolidatedfinancial statements referred to above present fairly, in all material respects, the financial position of the Company as of December 31, 2025 and 2024, and the results of itsoperations and itscash flows for each of the three years in the period ended December 31, 2025 in conformity with accounting principles generally accepted in the United States of America. Also in our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31, 2025, based on criteria established in Internal Control - Integrated Framework(2013)issued by the COSO.

Basis for Opinions

The Company's management is responsible for these consolidated financial statements, for maintaining effective internal control over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting, included inManagement's Annual Report on Internal Control over Financial Reporting appearing under Item 9A. Our responsibility is to express opinions on the Company’s consolidatedfinancial statements and on the Company's internal control over financial reporting based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the consolidatedfinancial statements are free of material misstatement, whether due to error or fraud, and whether effective internal control over financial reporting was maintained in all material respects.

Our audits of the consolidatedfinancial statements included performing procedures to assess the risks of material misstatement of the consolidatedfinancial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidatedfinancial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. Our audit of internal control over financial reporting included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing such other procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions.

Definition and Limitations of Internal Control over Financial Reporting

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

Critical Audit Matters

The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was communicated or required to be communicated to the audit committee and that (i) relates to accounts or

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disclosures that are material to the consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.

Revenue Recognition - PYRUKYND® Product Revenue

As described in Notes 2 and 8 to the consolidated financial statements, the Company generates product revenue from sales of 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 directly to patients. The performance obligation related to the sale of PYRUKYND® is satisfied and revenue is recognized when the Customer obtains control of the product, which occurs at a point in time, typically upon delivery to the Customer. Revenues from product sales are recorded at the net sales price, or transaction price, which includes estimates of variable consideration for which reserves are established and result from contractual adjustments, government rebates, returns and other allowances that are offered within the contracts with the Customers, healthcare providers, payors and other indirect customers relating to the sale of its products. For the year ended December 31, 2025, the Company recognized $54.0 million of net product revenue relating to the sale of PYRUKYND®.

The principal consideration for our determination that performing procedures relating to PYRUKYND® product revenue recognition is a critical audit matter is a high degree of auditor effort in performing procedures related to the Company’s product revenue recognition. Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements. These procedures included testing the effectiveness of controls relating to the revenue recognition process, including controls over the recording of PYRUKYND® product revenue at the transaction price once control passes to the customer. These procedures also included, among others, (i) evaluating management’s revenue recognition policy and (ii) testing the completeness, accuracy, and occurrence of revenue recognized for a sample of product revenue transactions by obtaining and inspecting source documents, such as purchase orders, invoices, proof of delivery, and subsequent cash receipts.

/s/ PricewaterhouseCoopers LLP

Boston, Massachusetts

We have served as the Company’s auditor since 2017.

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Agios Pharmaceuticals, Inc.

Consolidated Balance Sheets

(In thousands, except share and per share data) December 31: 2025 2024

Assets

Current assets:

Prepaid expenses and other current assets 44,130 40,165

Liabilities and stockholders’ equity

Current liabilities:

Income taxes payable — 871

Operating lease liabilities, net of current portion 21,815 40,207

Other non-current liabilities 90 880

Commitments and contingent liabilities (Note 14)

Stockholders’ equity:

Accumulated other comprehensive income (loss) 2,193 (1,518)

See accompanying Notes to Consolidated Financial Statements.

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Agios Pharmaceuticals, Inc.

Consolidated Statements of Operations

Revenues:

Operating expenses

Gain on sale of contingent payments — 889,136 —

Milestone payment from gain on sale of oncology business — 200,000 —

Net (loss) income per share - basic $ (7.12) $ 11.86 $ (6.33)

Net (loss) income per share - diluted $ (7.12) $ 11.64 $ (6.33)

See accompanying Notes to Consolidated Financial Statements.

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Agios Pharmaceuticals, Inc.

Consolidated Statements of Comprehensive (Loss) Income

Other comprehensive (loss) income

Unrealized gain (loss) on available-for-sale securities 3,711 (1,077) 12,094

See accompanying Notes to Consolidated Financial Statements.

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Agios Pharmaceuticals, Inc.

Consolidated Statements of Stockholders’ Equity

(In thousands, except share amounts) Shares Amount Shares Amount

Unrealized gain on available-for-sale securities — — — 12,094 — — — 12,094

Stock-based compensation expense — — 44,766 — — — — 44,766

Unrealized loss on available-for-sale securities — — — (1,077) — — — (1,077)

Stock-based compensation expense — — 42,847 — — — — 42,847

Unrealized gain on available-for-sale securities — — — 3,711 — — — 3,711

Stock-based compensation expense — — 52,552 — — — — 52,552

See accompanying Notes to Consolidated Financial Statements.

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Agios Pharmaceuticals, Inc.

Consolidated Statements of Cash Flows

Operating activities

Net accretion of discount on marketable securities (7,195) (14,486) (5,051)

Gain on sale of contingent payments — (889,136) —

Loss (gain) on disposal of property and equipment 5 (39) 553

Expense associated with license agreement 10,000 — 17,500

Realized gain on investments (118) (167) (28)

Milestone payment from gain on sale of oncology business — (200,000) —

Changes in operating assets and liabilities:

Prepaid expenses and other current and non-current assets (3,172) (5,811) 3,833

Income taxes payable (871) 871 —

Investing activities

Proceeds from sale of contingent payments — 889,136 —

Payments associated with license agreement (10,000) — (17,500)

Purchases of property and equipment (4,316) (1,685) (999)

Proceeds from sale of equipment — 40 1,325

Financing activities

Supplemental disclosure of non-cash investing and financing transactions:

See accompanying Notes to Consolidated Financial Statements.

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Agios Pharmaceuticals, Inc.

Notes to Consolidated Financial Statements

Note 1. Nature of Business

Note Regarding Certain References in this Annual Report on Form 10-K

Throughout this Annual Report on Form 10-K, “Agios,” “the Company,” “we,” “us,” and “our,” and similar expressions, except where the context requires otherwise, refer to Agios Pharmaceuticals, Inc. and its consolidated subsidiaries, and “our Board of Directors” refers to the board of directors of Agios Pharmaceuticals, Inc.

In addition, unless otherwise stated or the context indicates otherwise, all references in this Annual Report on Form 10-K to “AQVESMETM (mitapivat)” or “AQVESMETM” refer to our FDA-approved medicine for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in the United States; references to “PYRUKYND® (mitapivat)”, “PYRUKYND®”, or “mitapivat” refer to all other commercially available mitapivat products or mitapivat product candidates for which we are exploring further applications and indications, as the context requires.

Overview

We are subject to risks common to companies in our industry including, but not limited to, uncertainties relating to conducting preclinical and clinical research and development, the manufacture and supply of products for clinical and commercial use, obtaining and maintaining regulatory approvals and pricing and reimbursement for our products, market acceptance, managing global growth and operating expenses, availability of additional capital, competition, obtaining and enforcing patents, stock price volatility, dependence on collaborative relationships and third-party service providers, dependence on key personnel, potential litigation, potential product liability claims and potential government investigations.

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Alnylam License Agreement

In accordance with the license agreement, in the year ended December 31, 2023, we made an up-front payment to Alnylam and recognized in-process research and development of $17.5 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. 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.

Sale of Oncology Business to 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 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.

Liquidity

As of December 31, 2025, we had cash, cash equivalents and marketable securities of $1.2 billion. Although we have incurred recurring losses and expect to continue to incur losses for the foreseeable future, we expect our cash, cash equivalents and marketable securities to be sufficient to fund current operations for at least the next twelve months from the issuance of the financial statements. If we are unable to raise additional funds through equity or debt financings, we may be required to delay, limit, reduce or terminate product development or future commercialization efforts, or grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.

Note 2. Summary of Significant Accounting Policies

Principles of consolidation

The consolidated financial statements include our accounts and the accounts of our wholly owned subsidiaries, Agios Securities Corporation, Agios International Sarl (GmbH), Agios Germany GmbH, Agios Netherlands B.V., Agios Italy S.R.L., Agios

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France SARL, and Agios Limited. All intercompany transactions have been eliminated in consolidation. The consolidated financial statements have been prepared in conformity with U.S. generally accepted accounting principles, or U.S. GAAP.

Use of estimates

The preparation of our consolidated financial statements requires us to make estimates, judgments and assumptions that may affect the reported amounts of assets, liabilities, equity, revenues and expenses and related disclosure of contingent assets and liabilities. On an ongoing basis we evaluate our estimates, judgments and methodologies. We base our estimates on historical experience and on various other assumptions that we believe are reasonable, the results of which form the basis for making judgments about the carrying values of assets, liabilities and equity and the amount of revenues and expenses.

Cash and cash equivalents

We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value.

Accounts receivable, net

Our trade accounts receivable arise from product sales and represent amounts due from specialty distributors and specialty pharmacy providers in the U.S. and our distribution partners outside the U.S. We monitor the financial performance and creditworthiness of our customers so that we can properly assess and respond to changes in their credit profile. We reserve against these receivables for estimated losses that may arise from a customer’s inability to pay. Amounts determined to be uncollectible are charged or written-off against the reserve.

Inventory

Inventory is stated at the lower of cost or estimated net realizable value on a first-in, first-out basis. Prior to the regulatory approval of our product candidates, we incur expenses for the manufacture of drug product that could potentially be available to support the commercial launch of those products. Until the date at which regulatory approval has been received or is otherwise considered probable, we record all such costs as research and development expenses. Upon approval of our wholly owned product, PYRUKYND®, by the FDA on February 17, 2022 for the treatment of hemolytic anemia in adults with PK deficiency in the United States, we began to capitalize inventories of PYRUKYND®. Additionally, upon approval of our wholly owned product, AQVESMETM, by the FDA on December 23, 2025 for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in the United States, we began to capitalize inventories of AQVESMETM.

Revenue recognition

Product Revenue

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Cost of sales

Cost of sales consists primarily of manufacturing costs for sales of PYRUKYND®. Based on our policy to expense costs associated with the manufacturing of our products prior to regulatory approval, certain of the manufacturing costs associated with product shipments of PYRUKYND® recorded during the years ended December 31, 2025, 2024 and 2023 were expensed prior to February 17, 2022 and, therefore, are not included in costs of sales during the years ended December 31, 2025, 2024 and 2023. The amounts excluded from cost of sales were not significant during the years ended December 31, 2025, 2024 and 2023.

Marketable securities

Marketable securities at December 31, 2025 and 2024 consisted of investments in corporate debt securities, U.S. Treasuries, government securities, and certificates of deposit. We determine the appropriate classification of the securities at the time they are acquired and evaluate the appropriateness of such classifications at each balance sheet date. We classify our marketable securities as available-for-sale pursuant to ASC 320, Investments – Debt and Equity Securities. Marketable securities are recorded at fair value. Unrealized gains and losses are included as a component of accumulated other comprehensive income (loss) in the consolidated balance sheets and statements of stockholders’ equity and a component of total comprehensive (loss) income in the consolidated statements of comprehensive (loss) income, until realized. Realized gains and losses are included in interest income, net on a specific-identification basis.

At December 31, 2025 and 2024, we held both current and non-current investments. Investments classified as current are those that: (i) have a maturity of less than one year, or (ii) have a maturity of greater than one year but we intend to liquidate within the next twelve months. Investments classified as non-current are those that: (i) have a maturity of greater than one year, and (ii) we do not intend to liquidate within the next one year, although these funds are available for use and therefore classified as available-for-sale.

We review marketable securities for impairment whenever the fair value of a marketable security is less than the amortized cost and evidence indicates that a marketable security’s carrying amount is not recoverable. Unrealized losses are evaluated for

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impairment under ASC 326, Financial Instruments - Credit Losses, to determine if the impairment is credit-related or noncredit-related. Credit-related impairment is recognized as an allowance on the balance sheet with a corresponding adjustment to earnings, and noncredit-related impairment is recognized in other comprehensive (loss) income, net of taxes. Evidence considered in this assessment includes reasons for the impairment, compliance with our investment policy, the severity of the impairment, collectability of the security, and any adverse conditions specifically related to the security, an industry, or geographic area.

Fair value measurements

We record cash equivalents and marketable securities at fair value. ASC 820, Fair Value Measurements and Disclosures, establishes a fair value hierarchy for those instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and our own assumptions (unobservable inputs). The hierarchy consists of three levels:

Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities.

Level 2 – Quoted prices for similar assets and liabilities in active markets, quoted prices in markets that are not active, or inputs which are observable, either directly or indirectly, for substantially the full term of the asset or liability.

Level 3 – Unobservable inputs that reflect our own assumptions about the assumptions market participants would use in pricing the asset or liability in which there is little, if any, market activity for the asset or liability at the measurement date.

Our financial assets, which include cash equivalents and marketable securities, have been initially valued at the transaction price, and subsequently revalued at the end of each reporting period, utilizing third-party pricing services or other observable market data. The pricing services utilize industry standard valuation models, including both income and market based approaches, and observable market inputs to determine value. After completing our validation procedures, we did not adjust or override any fair value measurements provided by the pricing services as of December 31, 2025 or 2024. Fair value information for these assets, including their classification in the fair value hierarchy is included in Note 3, Fair Value Measurements.

There have been no changes to the valuation methods during the years ended December 31, 2025 and 2024. We evaluate transfers between levels at the end of each reporting period.

The carrying amounts of prepaid expenses and other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term maturities.

Concentrations of credit risk

Financial instruments which potentially subject us to credit risk consist primarily of cash, cash equivalents, and marketable securities. We hold these investments in highly rated financial institutions, and, by policy, limit the amounts of credit exposure to any one financial institution. These amounts at times may exceed federally insured limits. We have not experienced any credit losses in such accounts and do not believe we are exposed to any significant credit risk on these funds. We have no off-balance sheet concentrations of credit risk, such as foreign currency exchange contracts, option contracts, or other hedging arrangements.

Property and equipment

Property and equipment consist of laboratory equipment, computer equipment and software, leasehold improvements, furniture and fixtures, and office equipment. Costs of major additions and betterment are capitalized; maintenance and repairs, which do not improve or extend the life of the respective assets, are charged to expense as incurred. Upon retirement or sale, the cost of the disposed asset and the related accumulated depreciation are removed from the accounts and the resulting gain or loss is recognized.

Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:

Years

Laboratory equipment 5

Computer equipment and software 3

Furniture and fixtures 5

Office equipment 5

Leasehold improvements are amortized over the lesser of the remaining lease term or the estimated useful life of the improvement.

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Impairment of long-lived assets

We periodically evaluate our long-lived assets for potential impairment in accordance with ASC 360, Property, Plant and Equipment. Potential impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not be recovered. Recoverability of these assets is assessed based on the undiscounted expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trends and product development cycles. If impairments are identified, assets are written down to their estimated fair value. We did not recognize any impairment charges through December 31, 2025.

Leases

We determine if an arrangement is a lease at inception. An arrangement is determined to contain a lease if the contract conveys the right to control the use of an identified property or equipment for a period of time in exchange for consideration. If we can benefit from the various underlying assets of a lease on their own or together with other resources that are readily available, or if the various underlying assets are neither highly dependent on nor highly interrelated with other underlying assets in the arrangement, they are considered to be a separate lease component. In the event multiple underlying assets are identified, the lease consideration is allocated to the various components based on each of the component’s relative fair value.

Operating lease assets represent our right to use an underlying asset for the lease term and operating lease liabilities represent our obligation to make lease payments arising from the leasing arrangement. Operating lease assets and operating lease liabilities are recognized at commencement date based on the present value of lease payments over the lease term. As most of our leases do not provide an implicit rate, in determining the operating lease liabilities we use an estimate of our incremental borrowing rate. The incremental borrowing rate is determined using two alternative credit scoring models to estimate our credit rating, adjusted for collateralization. The calculation of the operating lease assets includes any lease payments made and excludes any lease incentives. Our lease terms may include options to extend or terminate the lease when it is reasonably certain that we will exercise that option.

For operating leases, we record operating lease assets and lease liabilities in our consolidated balance sheets. Lease expense for lease payments is recognized on a straight-line basis over the lease term. Short-term leases, or leases that have a lease term of 12 months or less at commencement date, are excluded from this treatment and are recognized on a straight-line basis over the term of the lease.

Research and development costs

Research and development costs, including those accrued as of each balance sheet date, are expensed as incurred. These costs include salaries and personnel-related costs, consulting fees, fees paid for contract research services, fees paid to contract research organizations, or CROs, and other third parties in connection with clinical trials and preclinical development activities, fees paid to investigative sites in connection with clinical trials, the costs associated with the product manufacturing, development, and distribution of clinical supplies, the costs of laboratory equipment and facilities, and other external costs.

Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. Additionally, there may be instances as of a given balance sheet date in which payments made to our vendors will exceed the level of services provided, and result in a prepayment of the research and development expense. The capitalized amounts are expensed as the related goods are delivered or the services are performed. We estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid accordingly.

Stock-based compensation

We account for stock-based compensation awards in accordance with ASC 718, Compensation –Stock Compensation, or ASC 718. For stock-based awards granted to employees, non-employees and members of the board of directors for their services and for participation in our employee stock purchase plan, we estimate the grant date fair value of each option award using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires us to make assumptions with respect to the expected term of the option, the expected volatility of the common stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject to service-based vesting conditions, we recognize stock-based compensation expense equal to the grant date fair value of stock options on a straight-line basis over the requisite service period. For awards subject to performance-based vesting conditions, we recognize stock-based compensation expense if the performance condition is considered probable of achievement using management’s best estimates.

Income taxes

Income taxes are recorded in accordance with ASC 740, Accounting for Income Taxes, or ASC 740, which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax

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consequences of events that have been included in our financial statements or tax returns. We determine our deferred tax assets and liabilities based on differences between the financial reporting and tax bases of assets and liabilities, which are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. Valuation allowances are provided, if based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.

We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.

Comprehensive (loss) income

Comprehensive (loss) income is defined as the change in equity of a business enterprise during a period from transactions, and other events and circumstances, and currently consists of net (loss) income and unrealized gains and losses on available-for-sale securities. Accumulated other comprehensive income (loss) consists entirely of unrealized gains and losses from available-for-sale securities as of December 31, 2025 and 2024.

Net (loss) income per share

Basic net (loss) income per share is calculated by dividing net (loss) income by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net (loss) income per share is calculated by adjusting the weighted-average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury stock method. For purposes of the dilutive net (loss) income per share calculation, stock options, restricted stock units, or RSUs, and performance-based stock units, or PSUs, for which the performance and market vesting conditions, respectively, have been deemed probable, and the Amended and Restated 2013 Employee Stock Purchase Plan shares are considered to be common stock equivalents, while PSUs with performance and market vesting conditions, respectively, that were not deemed probable as of December 31, 2025 are not considered to be common stock equivalents.

We utilize the control number concept in the computation of diluted earnings per share to determine whether potential common stock equivalents are dilutive. The control number used is net (loss) income from continuing operations. The control number concept requires that the same number of potentially dilutive securities applied in computing diluted earnings per share from continuing operations be applied to all other categories of income or loss, regardless of their anti-dilutive effect on such categories. Since we had a net loss for the years ended December 31, 2025 and 2023, no dilutive effect was recognized in the calculation of loss per share and basic and diluted net loss per share was the same for those periods.

Segment information

Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or CODM, or decision-making group in making decisions on how to allocate resources and assess performance. Our CODM is our chief executive officer, or CEO. Our CEO views our operations and manages our business as one operating segment, which derives its revenues from the development and commercialization of therapies for patients with rare diseases.

Treasury stock

Treasury stock purchases are accounted for under the cost method whereby the entire cost of the acquired stock is recorded as treasury stock. Repurchases of our common stock are accounted for as of the settlement date, and are held as treasury stock until they are retired or re-issued. There were no repurchases, retirements or re-issuances of treasury stock during the years ended December 31, 2025 and 2024.

Recent accounting pronouncements

In December 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standards Update, or ASU, 2023-09, Income Taxes (Topics 740): Improvements to Income Tax Disclosures, to expand the disclosure requirements for income taxes. Upon adoption, companies will be required to disclose additional specified categories in the rate reconciliation. Companies will also be required to disclose the amount of income taxes paid disaggregated by jurisdiction, among other disclosure requirements. The standard is effective for annual periods beginning after December 15, 2024, and can be applied either prospectively or retrospectively. We adopted the standard during our 2025 annual period and have included required disclosures in Note 11, Income Taxes.

In November 2024, the FASB issued ASU 2024-03, Income Statement – Reporting Comprehensive Income – Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses, to improve disclosures around

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an entity’s expenses. Upon adoption, companies will be required to disclose in the notes to the financial statements a disaggregation of certain expense categories included within the expense captions on the face of the income statement. The standard is effective for annual periods beginning after December 15, 2026 and interim periods beginning after December 15, 2027, with early adoption permitted, and can be applied either prospectively or retrospectively. We plan to adopt the standard in our 2027 annual period and are currently assessing its effect on our financial statement disclosures.

In September 2025, the FASB issued ASU No. 2025-07 Derivatives Scope Refinements and Scope Clarification for Share-Based Noncash Consideration from a Customer in a Revenue Contract. The amendments provide for a new scope exception to the derivatives guidance for underlyings based on the operations or activities specific to one of the parties to the contract, and also clarifies that share-based noncash consideration received from a customer as consideration for the transfer of goods or services in a revenue contract is subject to the revenue guidance and not the financial instruments guidance unless and until the company’s right to receive or retain the share-based noncash consideration is unconditional as defined in the ASU. The amendments are effective for annual reporting periods beginning after December 15, 2026, including interim periods within those fiscal years, with early adoption permitted. We plan to adopt the standard in the first quarter of 2026 and are currently assessing its effect on our consolidated financial statements.

Subsequent events

We considered events or transactions occurring after the balance sheet date, but prior to the issuance of the consolidated financial statements, for potential recognition or disclosure in our consolidated financial statements. All significant subsequent events have been properly disclosed in the consolidated financial statements.

Note 3. Fair Value Measurements

The following table summarizes our cash equivalents and marketable securities measured at fair value and by level (as described in Note 2, Summary of Significant Accounting Policies) on a recurring basis as of December 31, 2025:

(In thousands) Level 1 Level 2 Level 3 Total

Marketable securities:

Certificates of deposit — 751 — 751

We had no financial assets or liabilities that were classified as Level 3 at any point during the year ended December 31, 2025.

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Note 4. Marketable Securities

Marketable securities at December 31, 2025 consisted of the following:

(In thousands) AmortizedCost UnrealizedGains UnrealizedLosses FairValue

Current:

Certificates of deposit $ 750 $ 1 $ — $ 751

Non-current:

Marketable securities at December 31, 2024 consisted of the following:

(In thousands) AmortizedCost UnrealizedGains UnrealizedLosses FairValue

Current:

Non-current:

There were no material realized gains or losses on marketable securities for the years ended December 31, 2025 and 2024.

At December 31, 2025 and 2024, we held 37 and 213 debt securities, respectively, that were in an unrealized loss position for less than one year. We did not record an allowance for credit losses as of December 31, 2025 and 2024 related to these securities. The aggregate fair value of debt securities in an unrealized loss position at December 31, 2025 and 2024 was $136.2 million and $768.1 million, respectively. There were no individual securities that were in a significant unrealized loss position as of December 31, 2025 and 2024. We regularly review the securities in an unrealized loss position and evaluate the current expected credit loss by considering factors such as historical experience, market data, issuer-specific factors, and current economic conditions. We do not consider these marketable securities to be impaired as of December 31, 2025 and 2024.

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Note 5. Inventory

Inventory, which consists of commercial supply of PYRUKYND® and AQVESMETM, consisted of the following:

Raw materials $ 88 $ 89

Note 6. Leases

Our building leases are comprised of office and laboratory space under non-cancelable operating leases. These lease agreements have remaining lease terms of two years and contain various clauses for renewal at our option. The renewal options were not included in the calculation of the operating lease assets and the operating lease liabilities as the renewal options are not reasonably certain of being exercised. The lease agreements do not contain residual value guarantees.

We currently lease approximately 146,000 square feet at 88 Sidney Street, 43,000 square feet at 64 Sidney Street, and 13,000 square feet at 38 Sidney Street, Cambridge, Massachusetts. All leases, as amended, expire on February 29, 2028. At the end of the initial lease period, we have the option to extend the leases at all facilities for two consecutive five-year periods at the fair market rent at the time of the extension.

The components of lease expense and other information related to leases were as follows:

We have not entered into any material short-term leases or financing leases as of December 31, 2025.

In arriving at the operating lease liabilities as of December 31, 2025, we applied the weighted-average incremental borrowing rate of 5.7% from inception over a weighted-average remaining lease term of 2.2 years. In arriving at the operating lease liabilities as of December 31, 2024, we applied the weighted-average incremental borrowing rate of 5.7% over a weighted-average remaining lease term of 3.2 years.

As of December 31, 2025, undiscounted minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter, were as follows:

(In thousands)

Undiscounted minimum rental commitments 42,745

Total operating lease liabilities $ 40,207

We provided our landlord a security deposit of $2.9 million as security for our leases, which is included within other non-current assets on our consolidated balance sheet.

In August 2021, we entered into a long-term sublease agreement for 13,000 square feet of the office space at 38 Sidney Street, Cambridge, Massachusetts, which expired on December 31, 2024.

In April 2022, we entered into a long-term sublease agreement for 27,000 square feet of the office space at 64 Sidney Street, Cambridge, Massachusetts, which expired on April 30, 2025.

In May 2023, we entered into a long-term sublease agreement for 7,407 square feet of office space on the first floor of 64 Sidney Street, Cambridge, Massachusetts, which expired on July 31, 2025. In July 2025, we entered into a long-term sublease

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agreement with a new tenant for the same space, which began in November 2025 with the term of the lease running through February 2028.

We recorded operating sublease income of $1.9 million and $6.4 million for the years ended December 31, 2025 and December 31, 2024, respectively, in other income, net in the consolidated statements of operations. We hold security deposits from our sublessee of approximately $0.1 million which is recorded within other non-current assets on our consolidated balance sheet.

As of December 31, 2025, the future minimum lease payments to be received under the long-term sublease agreement was as follows:

(In thousands)

Note 7. Accrued Expenses

Accrued expenses consisted of the following at December 31:

Accrued research and development costs 12,081 10,548

Note 8. Product Revenue

Product revenue, net, was as follows for the years ended December 31:

Product revenue, net

One Customer accounted for 89%, 95% and 96% of our consolidated revenues for the years ended December 31, 2025, 2024 and 2023, respectively, and 55% and 92% of accounts receivable from product sales for the years ended December 31, 2025 and 2024, respectively.

Reserves for Variable Consideration

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AGIO US Equity

AGIO · 10-K · period ended 2025-12-31

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

Item 7A. Quantitative and Qualitative Disclosures about Market Risk

Item 8. Financial Statements and Supplementary Data

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

Item 9A. Controls and Procedures

Item 9B. Other Information

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections

Item 10. Directors, Executive Officers and Corporate Governance

Item 11. Executive Compensation

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

Item 13. Certain Relationships and Related Transactions, and Director Independence

Item 14. Principal Accountant Fees and Services

Item 15. Exhibits and Financial Statement Schedules

Item 16. Form 10-K Summary

AGIO US Equity☆

AGIO · 10-K · period ended 2025-12-31

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

Item 7A. Quantitative and Qualitative Disclosures about Market Risk

Item 8. Financial Statements and Supplementary Data

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

Item 9A. Controls and Procedures

Item 9B. Other Information

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections

Item 10. Directors, Executive Officers and Corporate Governance

Item 11. Executive Compensation

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

Item 13. Certain Relationships and Related Transactions, and Director Independence

Item 14. Principal Accountant Fees and Services

Item 15. Exhibits and Financial Statement Schedules

Item 16. Form 10-K Summary

AGIO US Equity