Agios Presents Data from Single Agent Dose-Escalation Arm of Phase 1 Study of AG-270, a MAT2A Inhibitor, in Patients with MTAP -Deleted Tumors Plasma SAM Biomarker Indicates Robust Target Engagement at Well Tolerated Dos

Agios Presents Data from Single Agent Dose-Escalation Arm of Phase 1 Study of AG-270, a MAT2A Inhibitor, in Patients with MTAP-Deleted Tumors

Plasma SAM Biomarker Indicates Robust Target Engagement at Well Tolerated Doses; AG-270 Maximum Tolerated Dose Determined to be 200 mg Once Daily

Combination Arms of Phase 1 Study Evaluating AG-270 in Combination with Taxanes in Non-Small Cell Lung Cancer and Pancreatic Cancer Initiated

Company to Host Investor

Event and Webcast Today at 6:30 p.m. ET

BOSTON, October 27, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a

leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today presented the first data from the single agent dose-escalation arm of the Phase 1 study of AG-270 in

methylthioadenosine phosphorylase (MTAP)-deleted tumors at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. AG-270 is an investigational, first-in-class methionine adenosyltransferase 2A (MAT2A) inhibitor.

The single agent arm of the Phase 1 trial for AG-270 provides the first data from a clinical study of a MAT2A

inhibitor, said Rebecca Heist, M.D., Massachusetts General Hospital and an investigator in the study. These data demonstrate that AG-270 induces reductions in the biomarkers of MAT2A inhibition,

notably plasma concentrations of S-adenosylmethionine (SAM) and tumor levels of symmetrically demethylated arginine (SDMA), at well tolerated doses. These findings will help guide the dosing and schedule for the next phase of development of AG-270 in combination with taxanes.

Inhibition of MAT2A is a unique approach to cancer treatment, based on

discoveries made by Agios scientists looking for differences in metabolism between cancer cells and normal cells, said Chris Bowden, M.D., chief medical officer at Agios. This early clinical work with

AG-270 confirms that it has the desired pharmacologic effects when given as single agent, and, supported by strong pre-clinical work and rationale, we are now enrolling

patients in two combination arms in homogenous patient populations to better understand AG-270 s clinical profile when combined with taxane-based regimens for

non-small cell lung and pancreatic cancer. These arms will be instrumental in gathering sufficient data to determine the next steps in clinical development.

AG-270 Phase 1 Study

The Phase 1 study of AG-270 in MTAP-deleted tumors began with a single agent dose-escalation arm to establish

the maximum tolerated dose of AG-270. Secondary objectives were to characterize AG-270 s safety, tolerability, pharmacokinetics and pharmacodynamics as a

monotherapy. Two additional Phase 1 arms were recently initiated to explore AG-270 in combination with taxanes in second-line non-small cell lung cancer and first or

second-line pancreatic cancer.

As of the August 16, 2019 data cutoff date, 39 patients had been treated in the single agent

dose-escalation arm with oral AG-270 either once or twice daily, at total daily doses ranging from 50 mg to 400 mg. The study enrolled patients with a wide range of advanced and treatment-refractory solid

tumors, including bile duct cancer (18%), pancreatic cancer (18%), mesothelioma (10%) and non-small cell lung cancer (10%). Nearly half of the patients enrolled had received three or more prior lines of

therapy. Thirty-six patients discontinued AG-270, primarily due to disease progression.

Pharmacokinetic and Pharmacodynamic Results

Safety and Efficacy Results

Next Steps for AG-270 Clinical Development

Patients are currently enrolling in the two combination arms of the Phase 1 study.

The goal of these arms is to further characterize the safety, tolerability, PK and PD, and to detect preliminary evidence of anti-tumor activity for the

Targeting MAT2A in Cancers with MTAP Deletion

Homozygous deletion of MTAP, the gene encoding the metabolic enzyme methylthioadenosine phosphorylase, occurs in ~15% of human malignancies. MTAP

deletion almost always coincides with the loss of cyclin-dependent kinase inhibitor 2A (CDKN2A), a well known negative prognostic factor in cancer. Deletion of MTAP results in the accumulation of the enzyme s substrate,

methylthioadenosine (MTA). Increased concentrations of MTA partially inhibit the activity of protein arginine methyltransferase 5 (PRMT5), while other methyltransferases are relatively unaffected. Further reduction of PRMT5 activity can be achieved

through modest reductions in the concentration of its normal substrate, the methyl donor S-adenosylmethionine (SAM). Inhibition of PRMT5 activity results in a reduction in symmetrically demethylated arginine residues (SDMAs) on target proteins, many

of which are involved in mRNA splicing. AG-270 is a first-in-class, oral, potent, reversible inhibitor of methionine

adenosyltransferase 2A (MAT2A), the key enzyme responsible for SAM synthesis.

Investor Event and Webcast Information

Agios will host an investor event today at 6:30 p.m. ET in Boston to review the AG-270 Phase 1 dose-escalation data and

pre-clinical research. The event will be webcast live and can be accessed under Events & Presentations in the Investors 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 cancer and rare genetic diseases through scientific leadership in the

field of cellular metabolism and adjacent areas of biology. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has two approved oncology precision medicines and multiple first-in-class investigational therapies 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.

About Agios/Celgene Collaboration

AG-270 is part of our 2016 global research collaboration agreement with Celgene Corporation focused on metabolic

immuno-oncology. Celgene has the option to participate in a worldwide 50/50 cost and profit share with Agios, under which Agios is eligible for up to $169 million in clinical and regulatory milestone payments for the program.

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: the potential benefits of AG-270; Agios plans for the further clinical development of AG-270 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; 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. 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.

Holly Manning, 617-844-6630

Associate Director, Investor Relations