UNITED STATES

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SCHEDULE 14A

(Rule 14a-101)

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Agios Pharmaceuticals, Inc.

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EMBRACING OUR PAST, REIMAGINING OUR FUTURE 39th Annual J.P. Morgan Healthcare Conference January 11, 2021 1EMBRACING OUR PAST, REIMAGINING OUR FUTURE 39th Annual J.P. Morgan Healthcare Conference January 11, 2021 1

Important Information for Investors and Stockholders Additional Information and Where to Find It This communication relates to the proposed transaction involving the sale by Agios Pharmaceuticals, Inc. (“Agios”) of its oncology business to Servier Pharmaceuticals, LLC. In connection with the proposed transaction, Agios will file relevant materials with the U.S. Securities and Exchange Commission (the “SEC”), including Agios’ proxy statement on Schedule 14A (the “Proxy Statement”). This communication is not a substitute for the Proxy Statement or any other document that Agios may file with the SEC or send to its stockholders in connection with the proposed transaction. BEFORE MAKING ANY VOTING DECISION, STOCKHOLDERS OF AGIOS ARE URGED TO READ ALL RELEVANT DOCUMENTS FILED WITH THE SEC, INCLUDING THE PROXY STATEMENT, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders will be able to obtain the documents (when available) free of charge at the SEC’s website, at http://www.sec.gov, and Agios’s website, at www.agios.com. In addition, the documents (when available) may be obtained free of charge by accessing Agios’s website at www.agios.com under the heading “Investors” or, alternatively, directing a request to Holly Manning by email at holly.manning@agios.com or by calling 617-649-8600. Participants in the Solicitation Agios and its directors and executive officers may be deemed to be participants in the solicitation of proxies from the holders of Agios common stock in respect of the proposed transaction. Information about the directors and executive officers of Agios is set forth in the proxy statement for Agios’ 2020 annual meeting of stockholders, which was filed with the SEC on April 16, 2020, and in other documents filed by Agios with the SEC. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the Proxy Statement and other relevant materials to be filed with the SEC in respect of the proposed transaction when they become available. 2Important Information for Investors and Stockholders Additional Information and Where to Find It This communication relates to the proposed transaction involving the sale by Agios Pharmaceuticals, Inc. (“Agios”) of its oncology business to Servier Pharmaceuticals, LLC. In connection with the proposed transaction, Agios will file relevant materials with the U.S. Securities and Exchange Commission (the “SEC”), including Agios’ proxy statement on Schedule 14A (the “Proxy Statement”). This communication is not a substitute for the Proxy Statement or any other document that Agios may file with the SEC or send to its stockholders in connection with the proposed transaction. BEFORE MAKING ANY VOTING DECISION, STOCKHOLDERS OF AGIOS ARE URGED TO READ ALL RELEVANT DOCUMENTS FILED WITH THE SEC, INCLUDING THE PROXY STATEMENT, WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders will be able to obtain the documents (when available) free of charge at the SEC’s website, at http://www.sec.gov, and Agios’s website, at www.agios.com. In addition, the documents (when available) may be obtained free of charge by accessing Agios’s website at www.agios.com under the heading “Investors” or, alternatively, directing a request to Holly Manning by email at holly.manning@agios.com or by calling 617-649-8600. Participants in the Solicitation Agios and its directors and executive officers may be deemed to be participants in the solicitation of proxies from the holders of Agios common stock in respect of the proposed transaction. Information about the directors and executive officers of Agios is set forth in the proxy statement for Agios’ 2020 annual meeting of stockholders, which was filed with the SEC on April 16, 2020, and in other documents filed by Agios with the SEC. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the Proxy Statement and other relevant materials to be filed with the SEC in respect of the proposed transaction when they become available. 2

Forward Looking Statements This communication contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Agios’ plans, strategies and expectations for the preclinical, clinical and commercial advancement of its drug development programs; the potential benefits of Agios’ products and product candidates; Agios’ key milestones and guidance for 2021 and strategic vision for 2025; its financial guidance regarding the period in which it will have capital available to fund its operations; expectations regarding the sale of Agios’ oncology portfolio and associated return of capital to shareholders; and the potential benefits of Agios’s strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. Management's expectations and, therefore, any forward-looking statements in this communication could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation risks and uncertainties related to: (i) Agios’s sale of its oncology portfolio, including the occurrence of any event, change or other circumstance that could give rise to the termination of the purchase and sale agreement; the failure of Agios to obtain stockholder approval for the proposed transaction or the failure to satisfy any of the other conditions to the completion of the proposed transaction; the effect of the announcement of the proposed transaction on the ability of Agios to retain and hire key personnel and maintain relationships with its customers, suppliers, advertisers, partners and others with whom it does business, or on its operating results and businesses generally; risks associated with the disruption of management’s attention from ongoing business operations due to the proposed transaction; the ability to meet expectations regarding the timing and completion of the proposed transaction, including with respect to receipt of required regulatory approvals; the failure of Agios to receive milestone or royalty payments under the purchase and sale agreement and the uncertainty of the timing of any receipt of any such payments; and the uncertainty of the results and effectiveness of the use of proceeds from the proposed transaction; (ii) the impact of the COVID-19 pandemic to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; (iii) Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; (iv) the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; (v) Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; (vi) unplanned cash requirements and expenditures and competitive factors; (vii) Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; (viii) Agios’ ability to maintain key collaborations; and (ix) general economic and market conditions. These and other risks are described in greater detail under the caption Risk Factors included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this communication speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. 3Forward Looking Statements This communication contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Agios’ plans, strategies and expectations for the preclinical, clinical and commercial advancement of its drug development programs; the potential benefits of Agios’ products and product candidates; Agios’ key milestones and guidance for 2021 and strategic vision for 2025; its financial guidance regarding the period in which it will have capital available to fund its operations; expectations regarding the sale of Agios’ oncology portfolio and associated return of capital to shareholders; and the potential benefits of Agios’s strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. Management's expectations and, therefore, any forward-looking statements in this communication could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation risks and uncertainties related to: (i) Agios’s sale of its oncology portfolio, including the occurrence of any event, change or other circumstance that could give rise to the termination of the purchase and sale agreement; the failure of Agios to obtain stockholder approval for the proposed transaction or the failure to satisfy any of the other conditions to the completion of the proposed transaction; the effect of the announcement of the proposed transaction on the ability of Agios to retain and hire key personnel and maintain relationships with its customers, suppliers, advertisers, partners and others with whom it does business, or on its operating results and businesses generally; risks associated with the disruption of management’s attention from ongoing business operations due to the proposed transaction; the ability to meet expectations regarding the timing and completion of the proposed transaction, including with respect to receipt of required regulatory approvals; the failure of Agios to receive milestone or royalty payments under the purchase and sale agreement and the uncertainty of the timing of any receipt of any such payments; and the uncertainty of the results and effectiveness of the use of proceeds from the proposed transaction; (ii) the impact of the COVID-19 pandemic to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; (iii) Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; (iv) the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; (v) Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; (vi) unplanned cash requirements and expenditures and competitive factors; (vii) Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; (viii) Agios’ ability to maintain key collaborations; and (ix) general economic and market conditions. These and other risks are described in greater detail under the caption Risk Factors included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this communication speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. 3

Shirley, Acute Myeloid Leukemia Tamara, Pyruvate Kinase Deficiency As always, we are driven by our sense of urgency to help patients. World Cholangiocarcinoma Day Panel 4 4 of Patients & Advocates Cass, Sickle Cell DiseaseShirley, Acute Myeloid Leukemia Tamara, Pyruvate Kinase Deficiency As always, we are driven by our sense of urgency to help patients. World Cholangiocarcinoma Day Panel 4 4 of Patients & Advocates Cass, Sickle Cell Disease

We are at an inflection point The path ahead is shaped by three important decisions: 1 2 3 Maximize the Thoughtfully Move forward value and impact pursue capital with a singular of our oncology markets focus on portfolio for independence genetically patients and while right-sizing defined diseases stakeholders the company 5We are at an inflection point The path ahead is shaped by three important decisions: 1 2 3 Maximize the Thoughtfully Move forward value and impact pursue capital with a singular of our oncology markets focus on portfolio for independence genetically patients and while right-sizing defined diseases stakeholders the company 5

To maximize the value and promise of our diverse portfolio, we have made a deliberate choice of where to focus our efforts and investment Selling our oncology portfolio to a capable and Expanding our committed buyer genetically defined allows us to disease pipeline maximize and mining the its patient impact. extensive, untapped potential in the PK franchise provides a clear path to success. By singularly focusing on genetically defined diseases and positioning our oncology portfolio for success with Servier, we can make the greatest impact. 6To maximize the value and promise of our diverse portfolio, we have made a deliberate choice of where to focus our efforts and investment Selling our oncology portfolio to a capable and Expanding our committed buyer genetically defined allows us to disease pipeline maximize and mining the its patient impact. extensive, untapped potential in the PK franchise provides a clear path to success. By singularly focusing on genetically defined diseases and positioning our oncology portfolio for success with Servier, we can make the greatest impact. 6

Our refocused therapeutic area is defined by a combination of our most differentiated foundational elements CELLULAR GENETICALLY METABOLISM DEFINED DISEASE GENETICALLY Cellular metabolism is a Genetically defined disease DEFINED DISEASES central part of our is a broad umbrella that + heritage and scientific encompasses both rare and CELLULAR competency more common diseases METABOLISM 7Our refocused therapeutic area is defined by a combination of our most differentiated foundational elements CELLULAR GENETICALLY METABOLISM DEFINED DISEASE GENETICALLY Cellular metabolism is a Genetically defined disease DEFINED DISEASES central part of our is a broad umbrella that + heritage and scientific encompasses both rare and CELLULAR competency more common diseases METABOLISM 7

Singular focus in genetically defined diseases sets the stage for building long- term value Mitapivat approvals in 3 initial indications Broad clinical pipeline of at least 5 molecules exploring at least 10 indications Initiate pivotal development of mitapivat Robust research pipeline in thalassemia and sickle cell disease poised to deliver a new IND every 12-24 months File NDA for mitapivat in PK deficiency; prepare for launch 2025 & Cash-flow positive Determine next steps for AG-946 development based on healthy Transformative Beyond deal with volunteer study Servier supports near-term Advance next research program to IND priorities 8Singular focus in genetically defined diseases sets the stage for building long- term value Mitapivat approvals in 3 initial indications Broad clinical pipeline of at least 5 molecules exploring at least 10 indications Initiate pivotal development of mitapivat Robust research pipeline in thalassemia and sickle cell disease poised to deliver a new IND every 12-24 months File NDA for mitapivat in PK deficiency; prepare for launch 2025 & Cash-flow positive Determine next steps for AG-946 development based on healthy Transformative Beyond deal with volunteer study Servier supports near-term Advance next research program to IND priorities 8

SERVIER TRANSACTION 9SERVIER TRANSACTION 9

The Servier transaction is the result of a comprehensive strategic review of our business and a competitive sale process We conducted a comprehensive strategic review of the company’s assets led by our board of directors and management team, with assistance from independent financial advisors, aimed at maximizing our potential for achieving superior outcomes for patients, and delivering sustainable, long-term value to shareholders We ran a broad, competitive process that included large biopharma, midsize biopharma with oncology growth strategies and regional biopharma with U.S. expansion strategies The consideration to be received from Servier captures the full intrinsic value of our oncology business – the significant upfront cash proceeds de-risks the oncology portfolio while the regulatory milestone and royalties provide significant participation in the future ® success of vorasidenib and TIBSOVO 10The Servier transaction is the result of a comprehensive strategic review of our business and a competitive sale process We conducted a comprehensive strategic review of the company’s assets led by our board of directors and management team, with assistance from independent financial advisors, aimed at maximizing our potential for achieving superior outcomes for patients, and delivering sustainable, long-term value to shareholders We ran a broad, competitive process that included large biopharma, midsize biopharma with oncology growth strategies and regional biopharma with U.S. expansion strategies The consideration to be received from Servier captures the full intrinsic value of our oncology business – the significant upfront cash proceeds de-risks the oncology portfolio while the regulatory milestone and royalties provide significant participation in the future ® success of vorasidenib and TIBSOVO 10

The recently announced deal with Servier captures the full value* of the oncology portfolio facilitating the acceleration of our efforts in genetically defined diseases Cash consideration of up to $2B, including $1.8B in upfront cash and a $200M milestone upon FDA approval of vorasidenib** 1 As part of the definitive agreement ® with Servier for the 5% royalties on U.S. net sales of TIBSOVO from acquisition of the transaction close through loss of exclusivity 2 oncology portfolio, Agios will receive: 15% royalties on U.S. net sales of vorasidenib from first commercial sale through loss of exclusivity 3 Agios plans to return at least $1.2B to shareholders; residual proceeds will be retained to achieve capital markets independence to fund the company through major catalysts and to profitability *Risk adjusted 11 11 **FDA approval of vorasidenib on or before January 1, 2027 with label permitting use as single agent in adjuvant setting for Grade 2 glioma with IDH1 or IDH2 mutationThe recently announced deal with Servier captures the full value* of the oncology portfolio facilitating the acceleration of our efforts in genetically defined diseases Cash consideration of up to $2B, including $1.8B in upfront cash and a $200M milestone upon FDA approval of vorasidenib** 1 As part of the definitive agreement ® with Servier for the 5% royalties on U.S. net sales of TIBSOVO from acquisition of the transaction close through loss of exclusivity 2 oncology portfolio, Agios will receive: 15% royalties on U.S. net sales of vorasidenib from first commercial sale through loss of exclusivity 3 Agios plans to return at least $1.2B to shareholders; residual proceeds will be retained to achieve capital markets independence to fund the company through major catalysts and to profitability *Risk adjusted 11 11 **FDA approval of vorasidenib on or before January 1, 2027 with label permitting use as single agent in adjuvant setting for Grade 2 glioma with IDH1 or IDH2 mutation

• Focusing solely on genetically defined diseases will enable us to drive greater differentiation for Agios, unlock a deeper pipeline of therapies and indications at a more rapid pace that leverage our core expertise in cellular metabolism The reimagined • Will realign capital structure to reflect stage of maturity based on our Agios presents a genetically defined disease pipeline with a plan to return at least compelling $1.2B of the $1.8B upfront proceeds; resulting in a share count investment reduction of approximately 25-35%* opportunity • Remaining proceeds together with our YE 2020 cash balance of $670.5M expected to be sufficient to fund company through major catalysts and to cash flow profitability in 2025 ® • TIBSOVO royalty and potential vorasidenib milestone and royalty Transaction subject to customary regulatory approvals and a shareholder approval; closing provide meaningful participation in these opportunities and expected in Q2 complementary sources of future cash flow *Assumes volume-weighted average repurchase price between $50-70 12 12• Focusing solely on genetically defined diseases will enable us to drive greater differentiation for Agios, unlock a deeper pipeline of therapies and indications at a more rapid pace that leverage our core expertise in cellular metabolism The reimagined • Will realign capital structure to reflect stage of maturity based on our Agios presents a genetically defined disease pipeline with a plan to return at least compelling $1.2B of the $1.8B upfront proceeds; resulting in a share count investment reduction of approximately 25-35%* opportunity • Remaining proceeds together with our YE 2020 cash balance of $670.5M expected to be sufficient to fund company through major catalysts and to cash flow profitability in 2025 ® • TIBSOVO royalty and potential vorasidenib milestone and royalty Transaction subject to customary regulatory approvals and a shareholder approval; closing provide meaningful participation in these opportunities and expected in Q2 complementary sources of future cash flow *Assumes volume-weighted average repurchase price between $50-70 12 12

Our plan accelerates and increases the impact we can make for patients, our employees and shareholders PATIENTS EMPLOYEES SHAREHOLDERS We will have the ability to make We will be a best-in-class Narrowed focus offers a difference for patients by: organization with a clear superior long-term vision and focus on genetically shareholder value creation • Shifting existing resources to defined diseases providing: driven by: execute on our PKD launch and rapidly advance our thalassemia and • An opportunity to bring three • A clearer path to sustained growth sickle cell disease programs mitapivat indications to market and profitability • Evaluating opportunities to broaden by 2025 • Significant upside potential as our PKR activator franchise and • The ability to work on a robust mitapivat and PK activation expand into non-PKR modalities and exciting research pipeline opportunities play out • Focusing our energy on the • A chance to amplify the best of • The return of at least $1.2B to promising targets within our research our existing culture with new shareholders to realign our capital organization opportunities to grow and make structure a difference • Capital markets independence • Placing our oncology portfolio with Servier, a company committed to investing in expanded indications and global reach for our programs 13Our plan accelerates and increases the impact we can make for patients, our employees and shareholders PATIENTS EMPLOYEES SHAREHOLDERS We will have the ability to make We will be a best-in-class Narrowed focus offers a difference for patients by: organization with a clear superior long-term vision and focus on genetically shareholder value creation • Shifting existing resources to defined diseases providing: driven by: execute on our PKD launch and rapidly advance our thalassemia and • An opportunity to bring three • A clearer path to sustained growth sickle cell disease programs mitapivat indications to market and profitability • Evaluating opportunities to broaden by 2025 • Significant upside potential as our PKR activator franchise and • The ability to work on a robust mitapivat and PK activation expand into non-PKR modalities and exciting research pipeline opportunities play out • Focusing our energy on the • A chance to amplify the best of • The return of at least $1.2B to promising targets within our research our existing culture with new shareholders to realign our capital organization opportunities to grow and make structure a difference • Capital markets independence • Placing our oncology portfolio with Servier, a company committed to investing in expanded indications and global reach for our programs 13

REIMAGINING OUR FUTURE 14REIMAGINING OUR FUTURE 14

Focused Innovation. Ambitious Development. AGIOS TOMORROW Increased Patient Impact. BY LEVERAGING WE CAN Culture Culture of of c continuo ontinuous us dev development elopment and and patient-first patient-first Deliver Deliver g groundbreaking roundbreaking science science with with an an orientation orientation energized energized focus and mission focus and mission Deep Deep understa understan nd diing ng o of f disease disease biology biology and and ex expertise pertise iin n cellular cellular Focus on metabo metabolism lism Fully Fully d develop potential evelop potential f for PK franchise or PK franchise Genetically and grow our clinical and grow our clinical p pipeline ipeline Defined Emphasis Emphasis on transla on translatio tion na all Diseases research, research, starting starting in early in early s stage tage discov discove ery ry Strengthen Strengthen the business the business Prov Proven success en success in drug in drug discov discove ery, ry, dev development elopment and and commercia commercializa lizat tion ion 15 15Focused Innovation. Ambitious Development. AGIOS TOMORROW Increased Patient Impact. BY LEVERAGING WE CAN Culture Culture of of c continuo ontinuous us dev development elopment and and patient-first patient-first Deliver Deliver g groundbreaking roundbreaking science science with with an an orientation orientation energized energized focus and mission focus and mission Deep Deep understa understan nd diing ng o of f disease disease biology biology and and ex expertise pertise iin n cellular cellular Focus on metabo metabolism lism Fully Fully d develop potential evelop potential f for PK franchise or PK franchise Genetically and grow our clinical and grow our clinical p pipeline ipeline Defined Emphasis Emphasis on transla on translatio tion na all Diseases research, research, starting starting in early in early s stage tage discov discove ery ry Strengthen Strengthen the business the business Prov Proven success en success in drug in drug discov discove ery, ry, dev development elopment and and commercia commercializa lizat tion ion 15 15

We are the pioneering leaders in PKR activation 6 YEARS STUDYING PKR ACTIVATION IN THE CLINIC ~190 17 15 17 3 DISEASES WITH JOURNAL ARTICLES MEDICAL/SCIENTIFIC PATIENTS CLINICAL PUBLISHED COLLABORATIONS POC ACHIEVED TREATED TRIALS st st st st 1 POSITIVE PHASE 1 GLOBAL PK 1 INTERNATIONAL PK 1 HEMOLYTIC A LOT 3 READOUT IN PK DEFICIENCY DEFICIENCY ANEMIA ADVOCACY DEFICIENCY REGISTRY ADVOCACY COUNCIL COALITION BUILDING OF FIRSTS: + 16We are the pioneering leaders in PKR activation 6 YEARS STUDYING PKR ACTIVATION IN THE CLINIC ~190 17 15 17 3 DISEASES WITH JOURNAL ARTICLES MEDICAL/SCIENTIFIC PATIENTS CLINICAL PUBLISHED COLLABORATIONS POC ACHIEVED TREATED TRIALS st st st st 1 POSITIVE PHASE 1 GLOBAL PK 1 INTERNATIONAL PK 1 HEMOLYTIC A LOT 3 READOUT IN PK DEFICIENCY DEFICIENCY ANEMIA ADVOCACY DEFICIENCY REGISTRY ADVOCACY COUNCIL COALITION BUILDING OF FIRSTS: + 16

In mitapivat, we are building a robust pipeline with the ability to rapidly expand to three indications Mitapivat Pipeline Overview Early Stage Late Stage Regulatory Near-Term Milestones Clinical Clinical Submission ~3-8K Non-transfusion Dependent Positive topline data from PATIENTS IN NDA filing in Q2; (NTD) Adult PK Deficiency (ACTIVATE) ACTIVATE announced in Dec. U.S. & EU5 MAA filing in 2H 2021 Transfusion Dependent Adult PK Deficiency Topline data expected in Q1 Pyruvate Kinase (ACTIVATE-T) 2021 Deficiency Finalize pivotal plan in 1H 2021; Sickle Cell Disease Initiate pivotal plan in 2021 ~18-23K Finalized pivotal plan in Dec. PATIENTS IN Non-transfusion Dependent Adult 2020; Initiate pivotal study U.S. & EU5 Thalassemia (ENERGIZE) in 2H 2021 Finalized pivotal plan in Dec. Transfusion Dependent Adult β- and 2020; Initiate pivotal study α-Thalassemia Thalassemia (ENERGIZE-T) in 2H 2021 Finalized pivotal plan in Dec. Pediatric PK Deficiency 2020 ~120-135K PATIENTS IN U.S. & EU5 Pediatric Thalassemia Planning in process Pediatric Sickle Cell Sickle Cell Disease Planning in process Disease 17In mitapivat, we are building a robust pipeline with the ability to rapidly expand to three indications Mitapivat Pipeline Overview Early Stage Late Stage Regulatory Near-Term Milestones Clinical Clinical Submission ~3-8K Non-transfusion Dependent Positive topline data from PATIENTS IN NDA filing in Q2; (NTD) Adult PK Deficiency (ACTIVATE) ACTIVATE announced in Dec. U.S. & EU5 MAA filing in 2H 2021 Transfusion Dependent Adult PK Deficiency Topline data expected in Q1 Pyruvate Kinase (ACTIVATE-T) 2021 Deficiency Finalize pivotal plan in 1H 2021; Sickle Cell Disease Initiate pivotal plan in 2021 ~18-23K Finalized pivotal plan in Dec. PATIENTS IN Non-transfusion Dependent Adult 2020; Initiate pivotal study U.S. & EU5 Thalassemia (ENERGIZE) in 2H 2021 Finalized pivotal plan in Dec. Transfusion Dependent Adult β- and 2020; Initiate pivotal study α-Thalassemia Thalassemia (ENERGIZE-T) in 2H 2021 Finalized pivotal plan in Dec. Pediatric PK Deficiency 2020 ~120-135K PATIENTS IN U.S. & EU5 Pediatric Thalassemia Planning in process Pediatric Sickle Cell Sickle Cell Disease Planning in process Disease 17

Significant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Anemia of chronic kidney disease Development candidates Retinal indications Diabetic retinopathy/nephropathy Hereditary myopathies PKM2 Neurologic (ALS) Others Aminoacidurias/acidemia: 6+ potential indications PAH Development candidate Phenylketonuria (~16,500 U.S. patients) Methylmalonic acidemia BCAT-II Propionic acidemia Others Multiple rare inborn errors of metabolism 18 Non-PK opportunities PK opportunitiesSignificant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Anemia of chronic kidney disease Development candidates Retinal indications Diabetic retinopathy/nephropathy Hereditary myopathies PKM2 Neurologic (ALS) Others Aminoacidurias/acidemia: 6+ potential indications PAH Development candidate Phenylketonuria (~16,500 U.S. patients) Methylmalonic acidemia BCAT-II Propionic acidemia Others Multiple rare inborn errors of metabolism 18 Non-PK opportunities PK opportunities

Significant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Data from the SAD/MAD cohorts for the AG-946 healthy volunteer study to be submitted for presentation by YE 2021 19 19Significant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Data from the SAD/MAD cohorts for the AG-946 healthy volunteer study to be submitted for presentation by YE 2021 19 19

Significant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Anemia of chronic kidney disease Development candidates Retinal indications Diabetic retinopathy/nephropathy Hereditary myopathies PKM2 Neurologic (ALS) Others Research efforts to prioritize new PKR and PKM2 indications for clinical development currently in process; development decisions to be made in 2021 20 20 PK opportunitiesSignificant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ Pyruvate kinase activation: 20+ potential indications program candidate new drug MAA Pyruvate kinase deficiency Sickle cell disease PKR α, β−Thalassemia mitapivat Hereditary spherocytosis (~64K U.S. patients) Anemia of low-risk MDS (~50K U.S. patients) AG-946 Multiple hereditary hemolytic anemias Anemia of chronic kidney disease Development candidates Retinal indications Diabetic retinopathy/nephropathy Hereditary myopathies PKM2 Neurologic (ALS) Others Research efforts to prioritize new PKR and PKM2 indications for clinical development currently in process; development decisions to be made in 2021 20 20 PK opportunities

Significant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ program candidate new drug MAA Aminoacidurias/acidemia: 6+ potential indications PAH Development candidate Phenylketonuria (~16,500 U.S. patients) Methylmalonic acidemia BCAT-II Propionic acidemia Others Multiple rare inborn errors of metabolism Development candidate declared and IND enabling activities for the PAH program ongoing Lead optimization in process for BCAT-II program 21 21 Non-PK opportunitiesSignificant opportunities exist beyond our initial pipeline focus Mechanism Molecule Approval Stage Indications Validated Development Investigational NDA/ program candidate new drug MAA Aminoacidurias/acidemia: 6+ potential indications PAH Development candidate Phenylketonuria (~16,500 U.S. patients) Methylmalonic acidemia BCAT-II Propionic acidemia Others Multiple rare inborn errors of metabolism Development candidate declared and IND enabling activities for the PAH program ongoing Lead optimization in process for BCAT-II program 21 21 Non-PK opportunities

Anticipated 2021 key milestones GDD PROGRAM MILESTONES GDD DATA PRESENTATIONS CORPORATE § Submit NDA in the U.S. for mitapivat in § Report topline data from the § Close the sale of the oncology portfolio adults with PK deficiency in Q2 ACTIVATE-T study of mitapivat in to Servier in Q2 regularly transfused PK deficiency § Commence the return of capital to § Submit MAA in the EU for mitapivat in in Q1 shareholders post-close in Q2 adults with PK deficiency in mid-2021 § Submit data from the mitapivat § Initiate two Phase 3 studies of ACTIVATE and ACTIVATE-T studies NEAR-TERM ONCOLOGY mitapivat – ENERGIZE-T and for presentation at EHA MILESTONES & DATA ENERGIZE – in regularly PRESENATIONS transfused and not regularly § Submit data from the mitapivat transfused thalassemia in 2H 2021 thalassemia Phase 2 study for § Achieve full-year revenue for presentation at EHA ® TIBSOVO of $160-170M § Provide an overview of our pivotal program for mitapivat in sickle cell § Submit data from ongoing clinical trials § Present mature OS for ClarIDHy at disease in 1H and initiate pivotal of mitapivat in sickle cell disease for ASCO GI on Jan. 17 program in 2021 presentation at medical meetings § Submit sNDA for TIBSOVO in throughout 2021 previously treated cholangiocarcinoma § Prioritize new PKR and PKM2 in Q1 indications for clinical development § Submit data from the SAD/MAD in 2021 cohorts of the AG-946 healthy § Complete enrollment in AGILE by YE volunteer study for presentation § Complete enrollment in the MDS at a medical meeting by YE cohort of the Phase 1 study by YE 22Anticipated 2021 key milestones GDD PROGRAM MILESTONES GDD DATA PRESENTATIONS CORPORATE § Submit NDA in the U.S. for mitapivat in § Report topline data from the § Close the sale of the oncology portfolio adults with PK deficiency in Q2 ACTIVATE-T study of mitapivat in to Servier in Q2 regularly transfused PK deficiency § Commence the return of capital to § Submit MAA in the EU for mitapivat in in Q1 shareholders post-close in Q2 adults with PK deficiency in mid-2021 § Submit data from the mitapivat § Initiate two Phase 3 studies of ACTIVATE and ACTIVATE-T studies NEAR-TERM ONCOLOGY mitapivat – ENERGIZE-T and for presentation at EHA MILESTONES & DATA ENERGIZE – in regularly PRESENATIONS transfused and not regularly § Submit data from the mitapivat transfused thalassemia in 2H 2021 thalassemia Phase 2 study for § Achieve full-year revenue for presentation at EHA ® TIBSOVO of $160-170M § Provide an overview of our pivotal program for mitapivat in sickle cell § Submit data from ongoing clinical trials § Present mature OS for ClarIDHy at disease in 1H and initiate pivotal of mitapivat in sickle cell disease for ASCO GI on Jan. 17 program in 2021 presentation at medical meetings § Submit sNDA for TIBSOVO in throughout 2021 previously treated cholangiocarcinoma § Prioritize new PKR and PKM2 in Q1 indications for clinical development § Submit data from the SAD/MAD in 2021 cohorts of the AG-946 healthy § Complete enrollment in AGILE by YE volunteer study for presentation § Complete enrollment in the MDS at a medical meeting by YE cohort of the Phase 1 study by YE 22

AGIOS 2025 VISION: Focused Innovation. Ambitious Development. Transformative Treatments for Patients with Genetically Defined Diseases. 5+ PIPELINE MITAPIVAT MOLECULES POISED TO APPROVALS CASH FLOW EXPLORING DELIVER NEW IN 3 INITIAL POSITIVE 10+ IND EVERY 12- INDICATIONS INDICATIONS 24 MONTHS 23 23AGIOS 2025 VISION: Focused Innovation. Ambitious Development. Transformative Treatments for Patients with Genetically Defined Diseases. 5+ PIPELINE MITAPIVAT MOLECULES POISED TO APPROVALS CASH FLOW EXPLORING DELIVER NEW IN 3 INITIAL POSITIVE 10+ IND EVERY 12- INDICATIONS INDICATIONS 24 MONTHS 23 23

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