AGIOS PHARMACEUTICALS INC

References to Agios

Throughout this Annual Report on Form 10-K, “the Company,” “Agios,” “we,” “us,” and “our,” and similar expressions, except where the context requires otherwise, refer to Agios Pharmaceuticals, Inc. and its consolidated subsidiaries, and “our board of directors” refers to the board of directors of Agios Pharmaceuticals, Inc.

Cautionary Note Regarding Forward-looking Information

This Annual Report on Form 10-K contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this Annual Report on Form 10-K, including statements regarding our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, and objectives of management, are forward-looking statements. The words “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 forward-looking statements, although not all forward-looking statements contain these identifying words.

The forward-looking statements in this Annual Report on Form 10-K include, among other things, statements regarding:

•our commercialization efforts and plans to commercialize PYRUKYND® (mitapivat);

•the initiation, timing, progress and results of current, planned and future preclinical studies and clinical trials, and our research and development programs;

•the potential of the isoforms of pyruvate kinase, including pyruvate kinase-R, or PKR, as therapeutic targets;

•the potential benefits of our products and product candidates targeting PKR, including PYRUKYND® (mitapivat) and tebapivat, and of our product candidate in our phenylalanine hydroxylase, or PAH, stabilizer program, AG-181, and our siRNA targeting the transmembrane serine protease 6, or TMPRSS6, gene, AG-236;

•our plans to develop and commercialize any additional product candidates for which we may receive approval, either alone or with partners;

•our ability to establish and maintain collaborations or to obtain additional funding, if needed;

•the timing or likelihood of regulatory filings and approvals, including our regulatory applications for approval of PYRUKYND® (mitapivat) for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia;

•our strategic vision;

•the timing, likelihood and amount of royalty payments we may receive from Servier Pharmaceuticals LLC with respect to certain U.S. net sales of vorasidenib;

•the amount and timing of future milestone and royalty payments potentially payable to Alnylam Pharmaceuticals, Inc. pursuant to the license agreement entered into in July 2023;

•the implementation of our business model and strategic plans for our business, product candidates and technology;

•our commercialization, sales, marketing and manufacturing capabilities and strategy;

•the rate and degree of market acceptance and clinical utility of our products;

•our competitive position;

•our intellectual property position;

•developments and projections relating to our competitors and our industry;

•our estimates regarding our expenses, future revenue, capital requirements and needs for additional financing; and

•the potential impact of public health epidemics or pandemics, global economic developments and geopolitical events on our business, operations, strategy and goals.

We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included important factors in this Annual Report on Form 10-K, particularly in the “Summary Risk Factors” and “Risk Factors” sections, that could cause actual results or events to differ materially from the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, in-licensing arrangements, mergers, dispositions, joint ventures or investments we may make.

You should read this Annual Report on Form 10-K and the documents that we have filed as exhibits to this Annual Report on Form 10-K completely. We do not assume any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

This Annual Report on Form 10-K includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this Annual Report on Form 10-K involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. We believe that the information from these industry publications, research, surveys and studies is reliable. The industry in which we operate is subject to a high degree of uncertainty and risk due to a variety of important factors, including those described in the sections titled “Summary Risk Factors” and “Risk Factors.”

Summary Risk Factors

Our business is subject to a number of risks that if realized could materially affect our business, financial condition, results of operations, cash flows and access to liquidity. These risks are discussed more fully in the “Risk Factors” section of this Annual Report on Form 10-K. Our principal risks include the following:

•If we do not successfully commercialize PYRUKYND® and other products for which we receive approval, our prospects may be substantially harmed. Our ability to generate product revenue from PYRUKYND® depends heavily on our successful development and commercialization of the product.

•We depend heavily on the success of our clinical-stage product candidates, including the potential approval of PYRUKYND® for the treatment of thalassemia or sickle cell disease, or SCD, in the United States and in other jurisdictions. Clinical trials of our product candidates may not be successful for a number of important reasons. If we or our collaborators are unable to commercialize our product candidates or experience significant delays in doing so, our business will be materially harmed.

•We may engage in in-licensing transactions or acquisitions that could disrupt our business, cause dilution to our stockholders or reduce our financial resources.

•The outcome of preclinical studies and early clinical trials may not be predictive of the success of later clinical trials, and positive results of completed clinical trials do not necessarily predict success in future clinical trials. The results of completed clinical trials of PYRUKYND® for the treatment of PK deficiency and thalassemia are not predictive of our ongoing clinical trials of PYRUKYND® in other indications, such as SCD, and the results of our early-stage clinical trials of tebapivat are not predictive of our later stage clinical trials of tebapivat.

•Interim and preliminary data from clinical trials that we announce or publish from time to time may change as more patient data becomes available and are subject to audit and verification procedures that could result in material changes in the final data.

•We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

•PYRUKYND®, or any of our product candidates that may receive marketing approval in the future, may be less effective than previously believed or cause undesirable side effects that were not previously identified in clinical trials or may fail to achieve the degree of market acceptance by physicians, patients, healthcare payors and others in the medical community necessary for commercial success, which could compromise our ability, or that of any collaborators, to market the product.

•If we are unable to establish and maintain sales and marketing capabilities or enter into agreements with third parties to sell and market our products, we may not be successful in commercializing PYRUKYND® or our product candidates if they are approved.

•We provide certain development estimates related to the development and regulatory approval of PYRUKYND® and our product candidates. If we do not achieve our projected development or regulatory approval estimates in the timeframes we announce and expect, the commercialization of our products may be delayed and, as a result, our stock price may decline.

•We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the indications for which we are developing PYRUKYND® or our product candidates. Our competitors may develop products that are more effective, safer, more convenient or less costly than PYRUKYND® or any product candidates that we are developing or that would render PYRUKYND® or our product candidates obsolete or non-competitive.

•We are singularly focused on products and product candidates for the treatment of rare diseases. As a result, we may be more susceptible to changing market conditions, including fluctuations and risks particular to the markets for patients with rare diseases, than a more diversified company, which could adversely affect our business, financial condition and results of operations.

•If our existing capital is insufficient to fund our operating expenses and capital expenditures, we will need to raise capital, and if we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

•We have historically incurred operating losses. We expect to incur losses in the future and may never achieve or maintain profitability. Our net income for the year ended December 31, 2024 was $673.7 million, our net loss for the year ended December 31, 2023 was $352.1 million and our net loss for the year ended December 31, 2022 was $231.8 million. The net income we generated in the year ended December 31, 2024 was primarily due to the sale of the Vorasidenib Royalty Rights to Royalty Pharma and our receipt of the Vorasidenib Milestone Payment discussed below in Item 1. Business. As of December 31, 2024, we had an accumulated deficit of $148.9 million.

•We currently rely and expect to continue to rely on third parties for the manufacture of our product candidates for preclinical and clinical testing and for commercial supply of PYRUKYND® and any product candidate for which we may obtain marketing approval. Any performance failure on the part of our existing or future third-party manufacturers could delay clinical development, marketing approval or our commercialization efforts.

•We rely and expect to continue to rely on third parties to conduct our clinical trials and some aspects of our research and preclinical testing, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials, research or testing.

•We may depend on collaborations with third parties for the development and commercialization of our product candidates. If those collaborations are not successful, we may not be able to capitalize on the market potential of these product candidates.

•If we are unable to obtain and maintain patent or trade secret protection for our medicines and technology, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize medicines and technology similar or identical to ours, and our ability to successfully commercialize our medicines and technology may be adversely affected. If we do not, or are unable to, obtain or maintain any issued patents for any of our most advanced product candidates, it could have a material adverse effect on our competitive position, business, financial condition, results of operations, and prospects.