Agios Pharmaceuticals Inc.
04/29/2026 | Press release | Distributed by Public on 04/29/2026 07:22
Quarterly Report for Quarter Ending March 31, 2026 (Form 10-Q)
Management's Discussion and Analysis of Financial Condition and Results of Operations
Forward-looking Information
The following discussion of our financial condition and results of operations should be read in conjunction with our unaudited condensed consolidated financial statements as of 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. This Management's Discussion and Analysis of Financial Condition and Results of Operations contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on current expectations, estimates, forecasts and projections, and the beliefs and assumptions of our management, and include, without limitation, statements with respect to our expectations regarding our research, development and commercialization plans and prospects, results of operations, selling, general and administrative expenses, research and development expenses, and the sufficiency of our cash for future operations. Words such as "aim," "anticipate," "believe," "continue," "could," "estimate," "expect," "goal," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "strategy," "target," "vision," "will," "would" or the negatives of these words and similar expressions are intended to identify these forward-looking statements, although not all forward-looking statements contain these identifying words. Readers are cautioned that these forward-looking statements are predictions and are subject to risks, uncertainties and assumptions that are difficult to predict. Therefore, actual results may differ materially and adversely from those expressed in any forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by our forward-looking statements are those discussed under the heading "Risk Factors" in Part II, Item 1A and elsewhere in this report, and in our Annual Report on Form 10-K for the year ended December 31, 2025. We undertake no obligation to revise the forward-looking statements contained herein to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law.
Overview
We are a commercial-stage biopharmaceutical company dedicated to redefining the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities, collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve.
The lead product candidate in our portfolio, mitapivat, is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias. Mitapivat is approved 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.
Sale of Oncology Business to Servier Pharmaceuticals, LLC (Servier) and Sale of Contingent Payments
In March 2021, we completed the sale of our oncology business to Servier Pharmaceuticals, LLC, or Servier. The transaction included the sale of our entire oncology business, including our clinical-stage product candidate vorasidenib, and included a royalty of 15% of U.S. net sales of vorasidenib from the first commercial sale of vorasidenib through loss of exclusivity, or the Vorasidenib Royalty Rights. The Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.
In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma Investments 2019 ICAV, or Royalty Pharma. The sale was contingent upon FDA approval of vorasidenib and other customary closing conditions.
Upon consummation of the sale in August 2024, Royalty Pharma acquired 100% of the Vorasidenib Royalty Rights payments made by Servier on account of up to $1.0 billion in U.S. net sales for each calendar year. In addition, any such Vorasidenib Royalty Rights payments made by Servier on account of U.S. net sales in each calendar year in excess of $1.0 billion will be split, with Royalty Pharma having the rights to a 12% earn-out on those excess payments and Agios retaining the rights to a 3% earn-out on those excess payments, or the Retained Earn-Out Rights. Royalty income related to the Retained Earn-Out Rights, if any, will be recognized in the period when realizable.
Financial Operations Overview
General
Since inception, our operations have primarily focused on organizing and staffing our company, business planning, raising capital, assembling our core capabilities in cellular metabolism and classical hematology, identifying potential product candidates, undertaking preclinical studies, conducting clinical trials, establishing a commercial infrastructure, preparing for and executing on the commercial launches of PYRUKYND® and AQVESME™ and, prior to the sale of our oncology business to Servier in March 2021, marketing TIBSOVO® and IDHIFA®. Through March 2021, we financed our operations primarily through proceeds from the sale of our royalty rights, commercial sales of TIBSOVO®, funding received from our collaboration agreements, private placements of our preferred stock, our initial public offering of our common stock and concurrent private placement of common stock to an affiliate of Celgene, and our follow-on public offerings. Following the sale of our oncology business to Servier in March 2021, we have financed and expect to continue to finance our operations primarily through cash on hand, potential royalty payments with respect to the Retained Earn-Out Rights, the actual and potential future sales of PYRUKYND® and AQVESME™ and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions. In addition, we may pursue opportunistic debt offerings, and equity or equity-linked offerings.
Additionally, since inception, we have historically incurred significant operating losses. Our net loss for the 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. We expect to continue to incur significant expenses and net losses until such time we are able to report profitable results. We may never achieve or maintain profitability, and our net losses may fluctuate significantly from year to year. We expect that we will continue to incur significant expenses as we continue to advance and expand our commercialization activities for PYRUKYND® and AQVESME™; continue to advance clinical development and regulatory activities for mitapivat, 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.
Revenues
Our wholly owned product, PYRUKYND®, received approval from the FDA on February 17, 2022, for the treatment of hemolytic anemia in adults with PK deficiency in the United States. Our wholly owned product, AQVESME™, received approval from the FDA on December 23, 2025, for the treatment of anemia in both non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia in the United States. Upon FDA approval of PYRUKYND® and AQVESME™ in the United States, we began generating product revenue from sales of PYRUKYND® and AQVESME™, respectively. We sell PYRUKYND® and AQVESME™ in the United States to a limited number of specialty distributors and specialty pharmacy providers. These customers subsequently resell PYRUKYND® and AQVESME™ to pharmacies or dispense PYRUKYND® and AQVESME™ directly to patients. In addition to distribution agreements with these customers, we enter into arrangements with healthcare providers and payors that provide for government-mandated and/or privately-negotiated rebates, chargebacks and discounts with respect to the purchase of PYRUKYND® and AQVESME™.
In July 2024, we entered into a distribution agreement, or the NewBridge 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 8, Product Revenue, to the condensed consolidated financial statements in this Quarterly Report on Form 10-Q.
In the future, we expect to continue to generate revenue from product sales of PYRUKYND® and AQVESME™. 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® 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.
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.
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
•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®/AQVESME™ (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.
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. 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. Mitapivat will continue to be marketed as PYRUKYND® in the United States for the PK deficiency indication, which does not require a REMS. The AQVESME™ REMS requires liver tests prior to the first AQVESME™ 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 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.
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 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. 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 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.
•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 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 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 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 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.
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®, AQVESME™ and any of our other product candidates, which may include the hiring of additional personnel.
Critical Accounting Estimates
Our critical accounting estimates are those which require the most significant judgments and estimates in the preparation of our condensed consolidated financial statements. 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.
Results of Operations
Comparison of the three months ended March 31, 2026 and 2025
Revenues
| Three Months Ended March 31, | ||||||||||||||
| (In thousands) | 2026 | 2025 | ||||||||||||
| Revenues: | ||||||||||||||
| Product revenue, net | ||||||||||||||
| United States | $ | 18,851 | $ | 8,726 | ||||||||||
| Rest of world | 1,895 | - | ||||||||||||
| Total product revenue, net | 20,746 | 8,726 | ||||||||||||
| Total revenue | $ | 20,746 | $ | 8,726 | ||||||||||
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 Operating Expenses
| Three Months Ended March 31, | ||||||||||||||
| (In thousands) | 2026 | 2025 | ||||||||||||
| Operating expenses: | ||||||||||||||
| Cost of sales | $ | 1,319 | $ | 1,085 | ||||||||||
| Research and development | 81,148 | 72,743 | ||||||||||||
| Selling, general and administrative | 48,304 | 41,527 | ||||||||||||
| Total operating expenses | $ | 130,771 | $ | 115,355 | ||||||||||
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.
Research and Development Expenses
Our research and development expenses, by major program, are outlined in the table below:
| Three Months Ended March 31, | |||||||||||
| (In thousands) | 2026 | 2025 | |||||||||
| PK activator (PYRUKYND®/AQVESME™) | $ | 23,905 | $ | 21,321 | |||||||
| Novel PK activator (tebapivat) | 5,925 | 5,388 | |||||||||
| PAH stabilizer (AG-181) | 968 | 382 | |||||||||
| siRNA targeting TMPRSS6 (AG-236) | 1,708 | 1,496 | |||||||||
| Other research and platform programs | 1,355 | 1,566 | |||||||||
| Total direct research and development expenses | 33,861 | 30,153 | |||||||||
| Compensation and related expenses | 36,789 | 32,990 | |||||||||
| Facilities and IT related expenses & other | 10,498 | 9,600 | |||||||||
| Total indirect research and development expenses | 47,287 | 42,590 | |||||||||
| Total research and development expense | $ | 81,148 | $ | 72,743 | |||||||
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.
Other Income and Expense
| Three Months Ended March 31, | |||||||||||
| (In thousands) | 2026 | 2025 | |||||||||
| Interest income, net | $ | 10,795 | $ | 16,087 | |||||||
| Other income, net | 119 | 1,253 | |||||||||
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.
Net Loss
| Three Months Ended March 31, | |||||||||||
| (In thousands) | 2026 | 2025 | |||||||||
| Net loss | $ | (99,111) | $ | (89,289) | |||||||
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.
Liquidity and Capital Resources
Sources of Liquidity
Since our inception, and through March 2021, we financed our operations primarily through proceeds from the sale of our royalty rights, commercial sales of TIBSOVO®, funding received from our collaboration agreements, private placements of our preferred stock, our initial public offering of our common stock and concurrent private placement of common stock to an affiliate of Celgene, and our follow-on public offerings. Following the sale of our oncology business to Servier in March 2021, we have financed and expect to continue to finance our operations primarily through cash on hand, potential royalty payments with respect to the Retained Earn-Out Rights, the actual and potential future sales of PYRUKYND® and AQVESME™ and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions. In addition, we may pursue opportunistic debt offerings, and equity or equity-linked offerings.
In March 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 and the Vorasidenib Royalty Rights. The Vorasidenib Royalty Rights are referred to as contingent payments and recognized as income when realizable.
In May 2024, we entered into a purchase and sale agreement to sell the Vorasidenib Royalty Rights to Royalty Pharma Investments 2019 ICAV, or Royalty Pharma. The sale was contingent upon FDA approval of vorasidenib and other customary closing conditions.
Upon consummation of the sale in August 2024, Royalty Pharma acquired 100% of the Vorasidenib Royalty Rights payments made by Servier on account of up to $1.0 billion in U.S. net sales for each calendar year. In addition, any such Vorasidenib Royalty Rights payments made by Servier on account of U.S. net sales in each calendar year in excess of $1.0 billion will be split, with Royalty Pharma having the rights to a 12% earn-out on those excess payments and Agios retaining the rights to a 3% earn-out on those excess payments, or the Retained Earn-Out Rights. Royalty income related to the Retained Earn-Out Rights, if any, will be recognized in the period when realizable.
Our cash, cash equivalents and marketable securities balance was $1.0 billion at March 31, 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.
Cash Flows
The following table provides information regarding our cash flows for the three months ended March 31, 2026 and 2025:
| Three Months Ended March 31, | |||||||||||
| (In thousands) | 2026 | 2025 | |||||||||
| Net cash used in operating activities | $ | (118,920) | $ | (111,489) | |||||||
| Net cash provided by investing activities | 141,312 | 112,587 | |||||||||
| Net cash provided by financing activities | 2,078 | 1,619 | |||||||||
| Net change in cash and cash equivalents | $ | 24,470 | $ | 2,717 | |||||||
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 interest 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.
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.
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.
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 AQVESME™ for their approved indications. 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. commercial launch of AQVESME™ in thalassemia, 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 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®, AQVESME™ 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 AQVESME™ 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® and AQVESME™ and, potentially, collaborations, strategic alliances, licensing arrangements and other nondilutive strategic transactions. In addition, we may pursue opportunistic debt offerings, and equity or equity-linked offerings. 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.
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.
Agios Pharmaceuticals Inc. published this content on April 29, 2026, and is solely responsible for the information contained herein. Distributed via EDGAR on April 29, 2026 at 13:23 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at [email protected]