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Item 2. Management’s Discussion and Analysis

2026-07-30 compared with 2026-04-29 · 117 added, 130 removed, 185 unchanged (57% of the section changed)

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Forward-looking Information

The following discussion of our financial condition and results of operations should be read in conjunction with our unaudited condensed consolidated financial statements as of March 31, 2026 and for the three months ended March 31, 2026 and 2025, and related notes included in Part I, Item 1 of this Quarterly Report on Form 10-Q, as well as the audited consolidated financial statements and notes and Management’s Discussion and Analysis of Financial Condition and Results of Operations, included in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the SEC on February 12, 2026.

The following discussion of our financial condition and results of operations should be read in conjunction with our unaudited condensed consolidated financial statements as of June 30, 2026 and for the three and six months ended June 30, 2026 and 2025, and related notes included in Part I, Item 1 of this Quarterly Report on Form 10-Q, as well as the audited consolidated financial statements and notes and Management’s Discussion and Analysis of Financial Condition and Results of Operations, included in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the SEC on February 12, 2026.

This Management’s Discussion and Analysis of Financial Condition and Results of Operations contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

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The lead product candidate in our portfolio, mitapivat, is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias.

Mitapivat is approved in the United States by the U.S.

Food and Drug Administration, or FDA, under the brand name AQVESME™ for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia and in Saudi Arabia and the United Arab Emirates 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 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 the first half of 2026.

In the first quarter of 2026, we presented data from the phase 2 and phase 3 portions of the RISE UP study of PYRUKYND® in adults with sickle cell disease, or SCD, in a pre-supplemental New Drug Application meeting with the FDA.

Based on the FDA’s recommendation, we submitted our proposal to the FDA for a confirmatory clinical trial to support U.S.

accelerated approval of mitapivat in SCD.

The proposal incorporates a primary endpoint that is different from the endpoints in the RISE UP studies and is informed by both analyses of RISE UP data and discussions with the FDA.

We intend to submit a supplemental New Drug Application, or sNDA, for mitapivat for SCD in the second quarter of 2026.

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.

Mitapivat is approved under the brand name AQVESME™ in the United States for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia.

Mitapivat is approved under the brand name PYRUKYND®:

in the United States for the treatment of hemolytic anemia in adults with PK deficiency;

in the European Union, or EU, for the treatment of PK deficiency and for the treatment of non-transfusion dependent and transfusion dependent alpha- or beta-thalassemia in adult patients;

in the Kingdom of Saudi Arabia for the treatment of adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia;

in the United Arab Emirates for the treatment of non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in adult patients;

and in Great Britain for the treatment of PK deficiency in adult patients.

We submitted a supplemental New Drug Application, or sNDA, for the U.S.

accelerated approval of mitapivat in sickle cell disease, or SCD, in May 2026, which was accepted with priority review by the FDA and granted a Prescription Drug User Fee Act, or PDUFA, goal date of November 1, 2026.

To support this accelerated approval pathway, we initiated REIGNITE, a phase 3 confirmatory trial designed to demonstrate the clinical benefit of mitapivat on reducing transfusion burden in patients with SCD aged 12 years or older.

Additionally, in the second quarter of 2026 we filed for regulatory approval for SCD in the Kingdom of Saudi Arabia.

We are also developing (i) AG-181, our phenylalanine hydroxylase, or PAH, stabilizer for the potential treatment of phenylketonuria, or PKU;

(ii) AG-236, an siRNA in-licensed from Alnylam Pharmaceuticals, Inc., or Alnylam, targeting the transmembrane serine protease 6, or TMPRSS6, gene for the potential treatment of polycythemia vera, or PV;

and (iii) cevidoplenib, an oral spleen tyrosine kinase, or SYK, inhibitor in-licensed from Oscotec Inc., or Oscotec, for the potential treatment of immune thrombocytopenia, or ITP, and other autoimmune indications.

Oscotec License Agreement

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

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

In accordance with the agreement, in the three months ended June 30, 2026, Agios made an up-front payment to Oscotec and recognized in-process research and development of $25.0 million, which was recorded in research and development expense within our Consolidated Statements of Operations and classified as investing activities within our Consolidated Statements of Cash Flows.

In addition, Agios is responsible to pay up to $140.0 million in potential development and regulatory milestones in the U.S.

and Europe, in addition to sales milestones as well as tiered royalties on future net sales, if any, of licensed products, which may be subject to specified reductions and offsets.

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

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Additionally, since inception, we have historically incurred significant operating losses.

Our net loss for the three months ended March 31, 2026 was $99.1 million and for the three months ended March 31, 2025 was $89.3 million.

As of March 31, 2026, we had an accumulated deficit of $660.8 million.

Our net loss for the six months ended June 30, 2026 was $199.8 million and for the six months ended June 30, 2025 was $201.3 million.

As of June 30, 2026, we had an accumulated deficit of $761.5 million.

We expect to continue to incur significant expenses and net losses until such time we are able to report profitable results.

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We expect that we will continue to incur significant expenses as we continue to advance and expand our commercialization activities for PYRUKYND® and AQVESME™;

continue to advance clinical development and regulatory activities for mitapivat, tebapivat, AG-181 and AG-236;

continue to advance clinical development and regulatory activities for mitapivat, AG-181, AG-236 and cevidoplenib;

expand and protect our intellectual property portfolio, including by in-licensing or acquiring assets for pipeline growth;

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Cost of sales consists primarily of manufacturing costs for sales of PYRUKYND® and AQVESME™.

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® and AQVESME™ recorded during the three months ended March 31, 2026 and 2025 were expensed prior to applicable regulatory approval, and, therefore, are not included in costs of sales during the three months ended March 31, 2026 and 2025.

The amounts excluded from cost of sales were not significant during the three months ended March 31, 2026 and 2025.

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® and AQVESME™ recorded during the three and six months ended June 30, 2026 and 2025 were expensed prior to applicable regulatory approval, and, therefore, are not included in costs of sales during the three and six months ended June 30, 2026 and 2025.

The amounts excluded from cost of sales were not significant during the three and six months ended June 30, 2026 and 2025.

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 three months ended March 31, 2026 and 2025.

We have not reserved for excess or obsolete inventory during the three and six months ended June 30, 2026 and 2025.

Research and Development Expenses

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• 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;

• 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;

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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.

Mitapivat was approved by the FDA 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 AQVESME™ for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia in the United States.

AQVESME™ is the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.

Mitapivat is approved under the brand name AQVESME™ in the United States for the treatment of anemia in adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia, and is the only FDA-approved medicine for anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.

We commercially launched AQVESME™ 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.

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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 addition, in March 2026, we announced that the Emirates Drug Establishment of the United Arab Emirates 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 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 the first half of 2026.

In the first quarter of 2026, we presented data from the phase 2 and phase 3 portions of the RISE UP study of PYRUKYND® in adults with SCD in a pre-supplemental New Drug Application meeting with the FDA.

Based on the FDA’s recommendation, we submitted our proposal to the FDA for a confirmatory clinical trial to support U.S.

accelerated approval of mitapivat in SCD.

The proposal incorporates a primary endpoint that is different from the endpoints in the RISE UP studies and is informed by both analyses of RISE UP data and discussions with the FDA.

We intend to submit an sNDA for mitapivat for SCD in the second quarter of 2026.

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.

Mitapivat is approved under the brand name PYRUKYND®:

in the United States for the treatment of hemolytic anemia in adults with PK deficiency;

in the EU for the treatment of PK deficiency and for the treatment of non-transfusion dependent and transfusion dependent alpha- or beta-thalassemia in adult patients;

in the Kingdom of Saudi Arabia for the treatment of adults with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia;

in the United Arab Emirates for the treatment of non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in adult patients;

and in Great Britain for the treatment of PK deficiency in adult patients.

We submitted an sNDA for the U.S.

accelerated approval of mitapivat in SCD in May 2026, which was accepted with priority review by the FDA and granted a PDUFA goal date of November 1, 2026.

Additionally, in the second quarter of 2026 we filed for regulatory approval for SCD in the Kingdom of Saudi Arabia.

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.

Additionally, 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 AQVESME™ and expect to fund the future development and commercialization costs related to PYRUKYND® and AQVESME™.

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 AQVESME™ in thalassemia in the United States.

In July 2024, we entered into the NewBridge Agreement with NewBridge, pursuant to which we granted NewBridge the right to commercialize PYRUKYND® in the GCC region.

In June 2025, we entered into the Avanzanite Agreement with 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 July 2024, we entered into the NewBridge Agreement, pursuant to which we granted NewBridge the right to commercialize PYRUKYND® in the GCC region.

In June 2025, we entered into the Avanzanite Agreement, 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, Saudi Arabia and the United Arab Emirates, 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.

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

• REIGNITE, a confirmatory clinical trial required to be conducted under the U.S.

accelerated approval pathway, to support our sNDA for mitapivat in SCD.

REIGNITE is a global phase 3 trial designed to demonstrate the clinical benefit of mitapivat on reducing transfusion burden in patients with SCD aged 12 years or older.

REIGNITE includes a 52-week, double-blind, randomized, placebo-controlled period, in which approximately 159 participants are randomized 2:1 to receive oral mitapivat (100 mg) twice daily or matched placebo.

Upon completing this period, participants have the option to transition into an open-label extension period where all such participants will receive mitapivat.

The primary endpoint of REIGNITE is the proportion of patients achieving transfusion-free status from Week 4 through Week 52, and the first key secondary endpoint is the number of red blood cell units transfused from Week 4 through Week 52.

To further assess the anti-hemolytic benefits of mitapivat, the trial also includes key secondary endpoints measuring the average change from baseline in hemoglobin, indirect bilirubin, and lactate dehydrogenase.

This trial is currently enrolling patients.

• 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 patients on mitapivat (n=134, 97.1%) and placebo (n=68, 98.6%) had adverse events;

(ii) serious treatment emergent adverse events, or 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.

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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 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.

In May 2026, we announced that we will not advance tebapivat in lower-risk myelodysplastic syndromes, or LR-MDS, as results from the phase 2b trial of tebapivat in LR-MDS did not meet our predefined threshold to support further development in the indication.

In July 2026, we announced that we will not continue development of tebapivat in SCD, as results from the phase 2 trial of tebapivat in SCD did not establish sufficient differentiation from other PK activators that we believe necessary to support continued development.

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 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 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 are developing AG-181, a PAH stabilizer for the potential treatment of PKU, for which we filed an 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 initiated a phase 1b trial of AG-181 in patients with PKU in the first half of 2026 and expect to confirm proof of mechanism in the second half of 2026.

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 initiated a phase 1 clinical trial evaluating AG-236 in healthy volunteers in July 2025.

We expect to announce topline data for this trial in the first half of 2026.

In June 2026, we announced topline results from the phase 1 clinical trial, which demonstrated dose-dependent hepcidin induction, sustained activity across doses, rapid and sustained biomarker changes and no dose-limiting toxicities.

We expect to initiate the phase 2 portion of a phase 2/3 trial of AG-236 in patients with PV in the second half of 2026.

In June 2026, we entered into a license agreement with Oscotec for the development, manufacture and commercialization of cevidoplenib, a novel, highly selective, oral SYK inhibitor in-licensed from Oscotec for the potential treatment of ITP and other autoimmune indications.

We expect to initiate a phase 3 clinical trial of cevidoplenib in patients with ITP in the first half of 2028, following completion of additional chemistry, manufacturing and controls development work.

Selling, General and Administrative Expenses

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We have determined that our most critical accounting estimates are those relating to revenue recognition, accrued research and development expenses and stock-based compensation.

As of March 31, 2026, there have been no material changes to our existing critical accounting estimates discussed in Part II, Item 7 of our Annual Report on Form 10-K for the year ended December 31, 2025.

As of June 30, 2026, there have been no material changes to our existing critical accounting estimates discussed in Part II, Item 7 of our Annual Report on Form 10-K for the year ended December 31, 2025.

Results of Operations

Comparison of the three months ended March 31, 2026 and 2025

Three Months Ended March 31,

Comparison of the three and six months ended June 30, 2026 and 2025

Three Months Ended June 30, Six Months Ended June 30,

(In thousands) 2026 2025 2026 2025

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Total revenue $ 44,745 $ 12,455 $ 65,491 $ 21,181

Total Revenue - Three Months Ended March 31, 2026 vs.

Three Months Ended March 31, 2025 – The increase in total revenue of $12.0 million for the three months ended March 31, 2026 compared to the three months ended March 31, 2025 was due to an increase of $10.1 million in United States product revenue and an increase of $1.9 million in rest of world product revenue.

The increase in United States product revenue was primarily due to increased volume associated with AQVESME™, which launched on December 23, 2025, and increased volume associated with PYRUKYND®.

The increase in rest of world product revenue was primarily due to increased volume associated with the Newbridge Agreement discussed above in Overview .

Total Revenue - Three Months Ended June 30, 2026 vs.

Three Months Ended June 30, 2025 – The increase in total revenue of $32.3 million for the three months ended June 30, 2026 compared to the three months ended June 30, 2025 was primarily due to an increase of $28.8 million in United States product revenue, which was primarily due to AQVESME™ sales, which we began recognizing product revenue for in the first quarter of 2026.

Total Revenue - Six Months Ended June 30, 2026 vs.

Six Months Ended June 30, 2025 – The increase in total revenue of $44.3 million for the six months ended June 30, 2026 compared to the six months ended June 30, 2025 was due to an increase of $38.9 million in United States product revenue and an increase of $5.4 million in rest of world product revenue.

The increase in United States product revenue was primarily due to AQVESME™ sales, which we began recognizing product revenue for in the first quarter of 2026, and increased volume associated with PYRUKYND®.

The increase in rest of world product revenue was primarily due to increased volume associated with the NewBridge Agreement and sales associated with the Avanzanite Agreement discussed above in Overview .

Total Operating Expenses

Three Months Ended March 31,

Three Months Ended June 30, Six Months Ended June 30,

(In thousands) 2026 2025 2026 2025

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Total operating expenses $ 155,297 $ 139,511 $ 286,068 $ 254,866

Total Operating Expenses - Three Months Ended March 31, 2026 vs.

Three Months Ended March 31, 2025 – The increase in total operating expenses of $15.4 million for the three months ended March 31, 2026 compared to the three months ended March 31, 2025 was primarily due to an increase in research and development expenses of $8.4 million, which is described below under Research and Development Expenses, and an increase in selling, general and administrative expenses of $6.8 million, driven by an increase in commercial-related activities as we execute our launch of AQVESME™ in thalassemia, and an increase in stock compensation expense.

Total Operating Expenses - Three Months Ended June 30, 2026 vs.

Three Months Ended June 30, 2025 – The increase in total operating expenses of $15.8 million for the three months ended June 30, 2026 compared to the three months ended June 30, 2025 was primarily due to an increase in research and development expenses of $8.8 million, which is described below under R esearch and Development Expenses , and an increase in selling, general and administrative expenses of $5.7 million, driven by an increase in commercial-related activities as we execute our launch of AQVESME™ in thalassemia.

Total Operating Expenses - Six Months Ended June 30, 2026 vs.

Six Months Ended June 30, 2025 – The increase in total operating expenses of $31.2 million for the six months ended June 30, 2026 compared to the six months ended June 30, 2025 was primarily due to an increase in research and development expenses of $17.2 million, which is described below under Research and Development Expenses , and an increase in selling, general and administrative expenses of $12.5 million, driven by an increase in commercial-related activities as we execute our launch of AQVESME™ in thalassemia, and an increase in stock compensation expense.

Research and Development Expenses

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

Three Months Ended March 31,

Three Months Ended June 30, Six Months Ended June 30,

(In thousands) 2026 2025 2026 2025

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siRNA targeting TMPRSS6 (AG-236) 2,839 2,426 4,547 3,922

In-process research and development 25,000 10,000 25,000 10,000

Other research and platform programs 694 1,304 2,049 2,870

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Total research and development expense $ 100,754 $ 91,940 $ 181,902 $ 164,683

Total Research and Development Expenses - Three Months Ended March 31, 2026 vs.

Three Months Ended March 31, 2025 – The increase in total research and development expenses of $8.4 million for the three months ended March 31, 2026 compared to the three months ended March 31, 2025 was due to a $4.7 million increase in our indirect expenses and a $3.7 million increase in our direct expenses.

The increase in our indirect expenses was primarily due to higher compensation and related expenses driven principally by workforce-related expenses.

The increase in direct expenses was primarily due to an increase in PYRUKYND®/AQVESME™ costs driven by higher process development expenses.

Total Research and Development Expenses - Three Months Ended June 30, 2026 vs.

Three Months Ended June 30, 2025 – The increase in total research and development expenses of $8.8 million for the three months ended June 30, 2026 compared to the three months ended June 30, 2025 was primarily due to an $8.0 million increase in our direct expenses.

The increase in direct expenses was primarily due to an increase in in-process research and development of $15.0 million, driven by the $25.0 million up-front payment associated with the agreement with Oscotec discussed above under Overview , partially offset by a decrease in PYRUKYND®/AQVESME™ costs of $4.0 million primarily due to lower process development expenses.

Total Research and Development Expenses - Six Months Ended June 30, 2026 vs.

Six Months Ended June 30, 2025 – The increase in total research and development expenses of $17.2 million for the six months ended June 30, 2026 compared to the six months ended June 30, 2025 was due to a $11.7 million increase in our direct expenses and a $5.5 million increase in our indirect expenses.

The increase in our indirect expenses was primarily due to higher compensation and related expenses driven principally by workforce-related expenses and an increase in stock compensation expenses.

Other Income and Expense

Three Months Ended March 31,

Three Months Ended June 30, Six Months Ended June 30,

(In thousands) 2026 2025 2026 2025

1 unchanged sentence

Other income, net 119 523 238 1,776

Other Income and Expense - Three Months Ended March 31, 2026 vs.

Three Months Ended March 31, 2025 – The decrease in interest income, net was due to a lower investment balance in the three months ended March 31, 2026 compared to the three months ended March 31, 2025 .

Three Months Ended March 31,

Other Income and Expense - Three Months Ended June 30, 2026 vs.

Three Months Ended June 30, 2025 – The decrease in interest income, net was due to a lower investment balance in the three months ended June 30, 2026 compared to the three months ended June 30, 2025 .

Other Income and Expense - Six Months Ended June 30, 2026 vs.

Six Months Ended June 30, 2025 – The decrease in interest income, net was due to a lower investment balance in the six months ended June 30, 2026 compared to the six months ended June 30, 2025 .

Three Months Ended June 30, Six Months Ended June 30,

(In thousands) 2026 2025 2026 2025

Net loss $ (100,703) $ (112,020) $ (199,814) $ (201,309)

Net Loss - Three Months Ended March 31, 2026 vs.

Three Months Ended March 31, 2025 – The increase in net loss for the three months ended March 31, 2026 compared to the three months ended March 31, 2025 was primarily driven by the increase in research and development expenses discussed above under Research and Development Expenses, the increase in selling, general and administrative expenses discussed above under Total Operating Expenses and the decrease in interest income, net discussed above in Other Income and Expense , partially offset by the increase in product revenue discussed above under Revenues .

Net Loss - Three Months Ended June 30, 2026 vs.

Three Months Ended June 30, 2025 – The decrease in net loss for the three months ended June 30, 2026 compared to the three months ended June 30, 2025 was primarily driven by the increase in product revenue discussed above under Revenues , partially offset by the increase in research and development expenses discussed above

under Research and Development Expenses, the increase in selling, general and administrative expenses discussed above under Total Operating Expenses and the decrease in interest income, net discussed above in Other Income and Expense.

Net Loss - Six Months Ended June 30, 2026 vs.

Six Months Ended June 30, 2025 – The decrease in net loss for the six months ended June 30, 2026 compared to the six months ended June 30, 2025 was primarily driven by the increase in product revenue discussed above under Revenues , partially offset by the increase in research and development expenses discussed above under Research and Development Expenses, the increase in selling, general and administrative expenses discussed above under Total Operating Expenses and the decrease in interest income, net discussed above in Other Income and Expense .

Liquidity and Capital Resources

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The Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.

In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma Investments 2019 ICAV, or Royalty Pharma.

In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma.

The sale was contingent upon FDA approval of vorasidenib and other customary closing conditions.

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Royalty income related to the Retained Earn-Out Rights, if any, will be recognized in the period when realizable.

Our cash, cash equivalents and marketable securities balance was $1.0 billion at March 31, 2026.

Our cash, cash equivalents and marketable securities balance was $1.0 billion at June 30, 2026.

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.

The following table provides information regarding our cash flows for the three months ended March 31, 2026 and 2025:

Three Months Ended March 31,

The following table provides information regarding our cash flows for the six months ended June 30, 2026 and 2025:

Six Months Ended June 30,

(In thousands) 2026 2025

4 unchanged sentences

Net cash used in operating activities.

Cash used in operating activities of $118.9 million during the three months ended March 31, 2026 was primarily due to operating expenses driven by research and development costs described above under Research and Development Expenses , partially offset by cash received from product revenues of $16.9 million and i nterest income of $12.4 million .

Cash used in operating activities of $111.5 million during the three months ended March 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 from interest income of $16.1 million and product revenues of $10.4 million.

Cash used in operating activities of $176.2 million during the six months ended June 30, 2026 was primarily due to operating expenses driven by research and development costs described above under Research and Development Expenses , partially offset by cash received from product revenues of $56.2 million and interest income of $22.1 million.

Cash used in operating activities of $188.6 million during the six months ended June 30, 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 from interest income of $31.5 million and product revenues of $22.0 million.

Net cash provided by investing activities .

Cash provided by investing activities of $141.3 million during the three months ended March 31, 2026 was primarily due to higher proceeds from maturities and sales of marketable securities than purchases of marketable securities.

Cash provided by investing activities of $112.6 million during the three months ended March 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 $181.5 million during the six months ended June 30, 2026 was primarily due to higher proceeds from maturities and sales of marketable securities than purchases of marketable securities.

Cash provided by investing activities of $191.6 million during the six months ended June 30, 2025 was primarily due to higher proceeds from maturities and sales of marketable securities than purchases of marketable securities.

Net cash provided by financing activities .

Cash provided by financing activities of $2.1 million during the three months ended March 31, 2026, was due to net proceeds received from stock option exercises and purchases made pursuant to our 2013 Employee Stock Purchase Plan, or 2013 ESPP.

Cash provided by financing activities of $1.6 million during the three months ended March 31, 2025, was due to net proceeds received from stock option exercises and purchases made pursuant to our 2013 ESPP.

Cash provided by financing activities of $5.2 million during the six months ended June 30, 2026 was due to net proceeds received from stock option exercises and purchases made pursuant to our Amended and Restated 2013 Employee Stock Purchase Plan, or 2013 ESPP.

Cash provided by financing activities of $1.7 million during the six months ended June 30, 2025, was due to net proceeds received from stock option exercises and purchases made pursuant to our 2013 ESPP.

Funding Requirements

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If we obtain additional marketing approvals for mitapivat in SCD 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 March 31, 2026, together with anticipated product revenue and interest income, will provide the financial independence to execute the U.S.

We expect that our existing cash, cash equivalents and marketable securities as of June 30, 2026, together with anticipated product revenue and interest income, will provide the financial independence to execute the U.S.

commercial launch of AQVESME™ in thalassemia, prepare for the potential U.S.

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• 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;

7 unchanged sentences

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.

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.

1 unchanged sentence

Contractual Obligations

During the three months ended March 31, 2026, there were no material changes to our contractual obligations and commitments described under Management's Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report on Form 10-K for the year ended December 31, 2025.

In June 2026, Agios entered into a license agreement with Oscotec as discussed above under Overview .

Under the license agreement, Agios is responsible to pay up to $140.0 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.

There were no other material changes to our contractual obligations and commitments described under Management's Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report on Form 10-K for the year ended December 31, 2025.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis