Agios Presents Positive Results from Phase 2 Study of Mitapivat in Non-transfusion-dependent - and -Thalassemia at the European Hematology Association Virtual Congress Study Met Primary Endpoint; Treatment with Mitapivat

Agios Presents Positive Results from Phase 2 Study of Mitapivat in

Non-transfusion-dependent - and -Thalassemia at the European Hematology Association Virtual Congress

Study Met Primary Endpoint; Treatment with Mitapivat Induced Hemoglobin Increase of

1.0 g/dL in 16 of 20 (80%) Patients During Weeks 4-12

Mitapivat Safety Profile Consistent with Previously Published Studies

Agios to Host Investor Webcast Today at 7:30 a.m. ET

CAMBRIDGE, Mass., June 11, 2021 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to

treat genetically defined diseases, today announced positive results from its Phase 2, open-label, multicenter study of mitapivat in adults with non-transfusion dependent - or -thalassemia. Data

from the study will be featured in an oral presentation on Tuesday, June 15, at the European Hematology Association (EHA) Virtual Congress.

Consistent with previously announced proof-of-concept data, the study

met its primary endpoint, with 16 of the 20 patients (80%) achieving a hemoglobin increase of 1.0 g/dL from baseline at one or more assessments during Weeks 4-12.

Additionally, a sustained hemoglobin response and improvements in hemolysis and ineffective erythropoiesis were observed in both - or -thalassemia patients treated with mitapivat. Mitapivat was well tolerated, and the safety profile was

consistent with previous studies. Mitapivat is a first-in-class, investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated

pyruvate kinase R (PKR) enzymes.

These data continue to validate the potential of PK activation as an entirely new mechanism for treating

thalassemia, a disease for which there have been few medical advancements. In particular, we are excited to see data generated, for the first time, in -thalassemia, demonstrating an increase in hemoglobin from baseline in all five patients in

this subgroup, said Kevin Kuo, M.D., hematologist at University Health Network, University of Toronto, and an investigator in the study. The impressive results reported today underscore the potential of mitapivat to meaningfully improve

hallmarks of this disease, including hemolysis and ineffective erythropoiesis.

Mitapivat Phase 2 Proof-of-concept Study

The open-label Phase 2 study evaluated the efficacy, safety, pharmacokinetics and

pharmacodynamics of mitapivat treatment in adults with either non-transfusion-dependent - or -thalassemia who have a baseline hemoglobin (Hb) concentration of

10 g/dL. The trial enrolled 20 patients. All patients were treated with an initial dose of mitapivat 50 mg twice daily followed by a dose-level increase to 100 mg twice daily at the Week 6 visit based on

safety evaluations and hemoglobin concentrations. Following the completion of the 24-week core

period, patients had the opportunity to enroll in an optional 10-year extension period which will evaluate long-term efficacy and safety of mitapivat in

The majority of adverse events (AEs)

observed were consistent with previously published data for mitapivat in healthy volunteers and patients with pyruvate kinase (PK) deficiency.

We are pleased to present data from our Phase 2 trial of mitapivat, which is the first clinical study

of a PK activator in thalassemia and the first drug trial in -thalassemia, and represents a potentially innovative therapeutic approach for these patients who are in need of new treatment options, said Chris Bowden, chief medical officer

at Agios. Our focus now is to advance the development of mitapivat in thalassemia as quickly and efficiently as possible, with the initiation of two Phase 3 studies of mitapivat, ENERGIZE and ENERGIZE-T,

in not regularly transfused and regularly transfused adults with thalassemia. Additionally, we look forward to further advancing mitapivat as a potential treatment for other underserved patients with hemolytic anemias, including individuals with

pyruvate kinase deficiency, where our U.S. and EU regulatory filing plans are on track, and sickle cell disease, where our pivotal development program is on track to initiate by year-end.

Oral Presentation Information

a Phase 2, open-label, multicenter study of the oral pyruvate kinase activator mitapivat in adults with non-transfusion dependent alpha- or beta-thalassemia

Live Q&A Session Date and Time: Tuesday, June 15, 2021, at 8:45 p.m. CEST / 2:45 p.m. ET

Oral Abstract Session: Changing the scene on thalassemias

Presenter: Kevin H. M. Kuo, M.D.,

Division of Hematology, University of Toronto, Toronto, Canada

Mitapivat Clinical Development

In addition to the Phase 2 extension study of mitapivat in adults with non-transfusion-dependent - and

-thalassemia, Agios is initiating two Phase 3 studies of mitapivat in adults with thalassemia in the second half of 2021. They are:

In addition to its Phase 2 study of mitapivat in adults with non-transfusion-dependent - or -thalassemia,

Agios has completed two global, pivotal trials in adults with pyruvate kinase (PK) deficiency. Final data from these studies will be presented in an oral session at the EHA Virtual Congress. They are:

ACTIVATE-T are intended to support global regulatory filings for mitapivat in adults with PK deficiency in the U.S. in the second quarter of 2021 and in the EU in

mid-2021. Agios also is conducting an extension study for adults with PK deficiency previously enrolled in ACTIVATE or ACTIVATE-T, which is designed to evaluate the

long-term safety, tolerability and efficacy of treatment with mitapivat.

In addition, mitapivat is being evaluated as a potential treatment for sickle

cell disease under a Cooperative Research and Development Agreement (CRADA) with the U.S. National Institutes of Health. Mitapivat has been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and increase adenosine triphosphate (ATP), and through this mechanism, it may reduce hemoglobin S polymerization and red blood cell sickling. Preliminary clinical data establishing proof-of-concept for mitapivat in sickle cell disease were disclosed in June 2020, and updated data were presented at the American Society of

Hematology (ASH) Annual Meeting in December 2020. Agios is initiating its pivotal Phase 2/3 study in sickle cell disease by year-end 2021.

Mitapivat has been granted orphan drug designation for the treatment of PK deficiency by the U.S. Food and Drug Administration (FDA) and

the European Medicines Agency. Additionally, mitapivat has received orphan drug designation from the FDA for the treatment of thalassemia and sickle cell disease.

Mitapivat is not approved for use by any regulatory authority.

CONFERENCE CALL INFORMATION

Agios will host a virtual

investor event today at 7:30 a.m. ET to review the mitapivat clinical data. The event will be webcast live and can be accessed under Events & Presentations in the Investors and Media section of the company s

website at www.agios.com. The archived webcast will be available on the company s website beginning approximately two hours after the event.

Agios is focused on discovering and

developing novel investigational medicines to treat genetically defined diseases through scientific leadership in the field of cellular metabolism. The company s most advanced drug candidate is a first-in-class pyruvate kinase R (PKR) activator, mitapivat, that is currently being evaluated for the treatment of three distinct hemolytic anemias. In addition to its active late-stage clinical pipeline,

Agios has multiple novel, investigational therapies in clinical and preclinical development. For more information, please visit the company s website at www.agios.com.

Cautionary Note Regarding Forward-Looking Statements

This press release 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, including mitapivat; the potential benefits of Agios products and

product candidates, including mitapivat; Agios key milestones and guidance for 2021; and the potential benefits of Agios 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 press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation risks and

uncertainties related to: the failure of Agios to receive milestone or royalty payments related to the sale of its oncology business, 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 transaction; 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 future approved products, and launching, marketing and selling future approved products;

Agios results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; 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; Agios ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials;

unplanned cash requirements and expenditures and competitive factors; Agios ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios ability to establish

and maintain collaborations; and 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, or SEC, including the risks and uncertainties set forth under the heading Risk Factors in our filings with the SEC. While the list of factors presented here is considered representative, this list should not be considered to be

a complete statement of all potential risks and uncertainties. Any forward-looking statements contained in this communication are made only as of the date hereof, and we undertake no obligation to update forward-looking statements to reflect

developments or information obtained after the date hereof and disclaim any obligation to do so other than as may be required by law.