Agios Announces New Data from AG-348 and AG-519 Demonstrating Potential for First Disease-modifying Treatment for Patients with PK Deficiency - AG-348 Is Well-Tolerated and Demonstrates Clinically Relevant, Rapid and Sus

Agios Announces New Data from AG-348 and AG-519 Demonstrating Potential for First

Disease-modifying Treatment for Patients with PK Deficiency

- AG-348 Is Well-Tolerated and Demonstrates Clinically Relevant, Rapid and Sustained Hemoglobin Increases in 15 of 26 Patients with at Least

One Missense Mutation and 15 out of 32 Patients Overall -

- AG-519 Is Well-Tolerated and Demonstrates Robust Dose-Dependent Changes

in ATP and 2,3-DPG Blood Levels in Normal Healthy Volunteers Consistent with PKR Enzyme Activation -

Investor Event and Webcast Today at 8:00 p.m. PT -

SAN DIEGO, December 4, 2016 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO) presented new

data on two molecules from its wholly owned PKR activator program demonstrating the potential for the first disease-modifying treatment for patients with PK Deficiency at the 2016 American Society of Hematology Annual Meeting and Exposition

(ASH). Agios PKR program consists of AG-348, which is being evaluated in the Phase 2 DRIVE PK study in patients with pyruvate kinase (PK) deficiency, and AG-519, a second PKR activator being evaluated in an ongoing Phase 1 trial in healthy

volunteers. PK deficiency is a rare, potentially debilitating, congenital anemia. Data from these studies were last reported at the Congress of the European Hematology Association (EHA) in June 2016.

Updated data from DRIVE PK with additional patients and longer follow-up demonstrate that 47% of all efficacy evaluable patients (n=15/32) and 58% of

evaluable patients with at least 1 missense mutation (n=15/26) treated with AG-348 experienced a maximum hemoglobin (Hb) increase from baseline of >1.0 gram per deciliter (g/dL). Efficacy evaluable patients were required to have received AG-348

for at least three weeks. Hb increases >1.0 g/dL were observed in patients randomized to two doses and the maximum increase ranged from 1.2 5.2 g/dL with a mean maximum increase of 3.6 g/dL. Hb increases were also rapid and sustained, with a

median time to a hemoglobin increase of >1.0 g/dL of 1.4 weeks. Agios also presented the first data demonstrating a direct link between increases in hemoglobin levels and activation of the PKR pathway (rate of metabolism) in patients treated with

In addition, data from the ongoing Phase 1 trial in healthy volunteers establish that AG-519 is well-tolerated and demonstrates clear

proof-of-mechanism as a potent, oral, selective PKR activator. The robust dose-dependent changes in ATP (adenosine triphosphate) and 2,3-DPG (2,3-diphosphoglycerate) blood levels reported with AG-519 are consistent with PKR enzyme activation. The

activity of AG-519 as an activator of both wild-type and mutant forms of PKR is similar to that of AG-348.

With data from additional patients and

longer follow-up, it is highly encouraging that AG-348 continues to demonstrate robust, rapid and sustained increases in hemoglobin in patients with PK

deficiency, said Rachael Grace, M.D., of the Dana-Farber Boston Children s Cancer and Blood Disorder Center and a principal investigator for the study. These findings are

important for physicians and patients as they offer the potential for the first disease-modifying treatment for patients suffering from this chronic anemia and its associated complications.

The rapid and sustained hemoglobin increases shown in DRIVE PK and AG-519 s robust PK/PD profile continue to support moving a PKR activator into

pivotal development next year, said Chris Bowden, M.D., chief medical officer at Agios. In addition, our scientists continue to lead advances in the understanding of the biology of PK deficiency and have demonstrated the first data

linking an increase in hemoglobin to direct activation of the PKR pathway.

Updated Phase 2 DRIVE-PK Data for AG-348

DRIVE PK is a global Phase 2, open-label safety and efficacy trial and the first study evaluating AG-348 in adult, transfusion-independent patients with PK

deficiency. The study includes two arms of approximately 25 patients each, receiving a dose of 50 milligrams (mg) or 300 mg twice daily for at least six months (24 weeks). The target enrollment has been reached with a total of 52 patients enrolled.

As of the September 23, 2016 data cut-off:

A safety analysis was

conducted based on all 34 treated patients as of the data cut-off.

In the efficacy analysis

(n=32), 15 of 32 total evaluable patients and 15 of 26 evaluable patients with at least one missense mutation achieved rapid, robust and sustained hemoglobin increases from baseline of >1.0 g/dL as of the data cut-off.

Healthy Volunteer Study Results for AG-519

Data were reported from four single ascending dose (SAD) cohorts of healthy volunteers (eight per group, 32

volunteers total) receiving daily doses of 50 mg, 250 mg, 750 mg or 1250 mg of AG-519 or placebo. Data were also reported from five multiple ascending dose (MAD) cohorts of healthy volunteers (eight per group, 40 volunteers total) dosed twice daily

with 10 mg, 25 mg, 125 mg, 300 mg or 375 mg of AG-519 or placebo for 14 days.

About Pyruvate Kinase Deficiency and Genetic Background

PK deficiency is a rare inherited disease that presents as hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutations

in PKR enzymes cause a deficit in cellular energy within the red blood cell, as evidenced by lower pyruvate kinase enzyme activity and a decline in ATP levels and a build-up of upstream metabolites, including 2,3-DPG.

The current standard of care for PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or

interventions for other treatment- and disease-related morbidities. There is no approved therapy to treat the underlying cause of PK deficiency.

deficiency is an autosomal recessive disease whereby all patients inherit two mutations, one from each parent. More than 250 different mutations have been identified to date. The mutations observed in PK deficiency patients are classified in two

main categories. A missense mutation causes a single amino acid change in the protein, generally resulting in some functional protein. A non-missense mutation is any mutation other than a missense mutation, generally resulting in little functional

protein. It is estimated that 53 percent of patients with PK deficiency have two missense mutations, 25 percent have one missense and one non-missense mutation, and 22 percent have two non-missense mutations1.

Boston Children s Hospital, in collaboration with Agios, is conducting a Natural History Study to

better understand the symptoms and complications of PK deficiency, identify patients and treatment centers, and capture other clinical data, including quality of life measures and genetic information.

About Agios PKR Activators

Agios has discovered

and is currently evaluating two orally available, potent, selective small molecule activators of PKR in clinical trials, AG-348 and AG-519. Agios scientists previously reported that AG-348 is a potent activator of the wild-type and mutated PKR

enzymes in humans. Agios retains worldwide development and commercialization rights to AG-348 and AG-519.

Investor Event and Webcast Information

Agios will host an investor event on Sunday, December 4, 2016 beginning at 8:00 p.m. PT (11:00 p.m. ET) in San Diego to review data presented at ASH,

including new data from the

ongoing studies of AG-348 and AG-519. 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.

focused on discovering and developing novel investigational medicines to treat cancer and rare genetic metabolic disorders through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline

across both therapeutic areas, Agios has multiple first-in-class investigational medicines in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism,

biology and genomics. For more information, please visit the company s website at www.agios.com.

Cautionary Note Regarding Forward-Looking

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: the potential benefits of Agios product candidates targeting pyruvate kinase-R mutations, including AG-348 and AG-519; Agios plans for the further clinical development of AG-348 and

AG-519; and Agios strategic plans and prospects. The words anticipate, believe, estimate, expect, intend, may, plan, predict, project,

would, could, potential, possible, hope 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. For example, there can be no guarantee that any

product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases; that positive safety and efficacy findings observed in early stage clinical trials will be replicated in later stage

trials; or that development of any of Agios product candidates will successfully continue. There can be no guarantee that any positive developments in Agios business will result in stock price appreciation. 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: 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 and 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; 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 maintain key collaborations, such as its agreements with Celgene; and general economic and market

conditions. These and other risks are described in greater detail under the caption Risk Factors included in Agios Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, and other filings that Agios may

make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release 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.

Kendra Adams, 617-844-6407

Senior Director, Investor & Public Relations

Renee Leck, 617-649-8299

Senior Manager, Investor & Public Relations

Dan Budwick, 973-271-6085

Senior Vice President, Media Relations

Pure Communications Inc.