Business Transactions - The company completed the sale of its oncology business to Servier Pharmaceuticals for approximately $1.8 billion in cash, with potential additional payments of $200 million and royalties of 5% and 15% on U.S. net sales of TIBSOVO® and vorasidenib, respectively[10]. - The company received approximately $1.8 billion in cash from the sale of its oncology business to Servier, with additional contingent payments based on regulatory approvals and sales performance[111]. - The company has classified the results of its oncology business as discontinued operations following its sale in Q1 2021[172]. Product Development and Approvals - PYRUKYND® (mitapivat) was approved by the FDA in February 2022 for treating hemolytic anemia in adults with pyruvate kinase deficiency, with a commercial launch expected in Q1 2022[11]. - The company is developing AG-946, a next-generation PK activator, for potential treatment of hemolytic anemias and other indications, including sickle cell disease[11]. - PYRUKYND® has been approved by the FDA for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency, with ongoing regulatory review in the EU[28]. - The company submitted a Marketing Authorization Application (MAA) to the EMA in June 2021 for the same indication in the European Union[95]. - The company expects to initiate two phase 3 trials of PYRUKYND® in pediatric patients with PK deficiency in mid-2022[163]. - AG-946, a next-generation PKR activator, is currently in a phase 1 trial with healthy volunteers, and the SCD patient cohort is expected to begin in the first half of 2022[163]. Financial Performance - The company reported a net income of $1,604.7 million for the year ended December 31, 2021, primarily due to the sale of its oncology business to Servier on March 31, 2021[160]. - The accumulated deficit as of December 31, 2021, was $238.8 million, with net losses of $327.4 million and $411.5 million for the years ended December 31, 2020, and 2019, respectively[160]. - PYRUKYND® revenue for 2021 was $73.999 million, up from $48.669 million in 2020, representing a 52% increase[175]. - Total operating expenses increased by $42.5 million in 2021 compared to 2020, primarily due to a $36.2 million increase in research and development expenses[174]. Research and Development - The company aims to achieve cash flow positivity and advance at least five internally discovered molecules in clinical development spanning at least ten indications over the next five years[14]. - The company expects research and development costs related to its genetically defined disease portfolio to increase significantly as product candidate development programs progress[161]. - The company has built its U.S. commercial infrastructure to support the launch of PYRUKYND® and is exploring partnership opportunities for commercialization outside the U.S.[161]. Regulatory and Compliance - The company must navigate extensive regulatory processes for drug approval, which require substantial time and financial resources[39]. - The FDA requires compliance with post-approval regulatory requirements, including reporting adverse reactions and manufacturing problems[54]. - The company emphasizes the importance of maintaining its proprietary and intellectual property position through effective patent claims and enforcement[35]. - The company is committed to identifying and qualifying additional manufacturers for its product candidates prior to submitting a New Drug Application (NDA) to the FDA[38]. Market and Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies, including Bristol-Myers Squibb, Merck, and Pfizer, among others, in the development of therapies for genetic diseases[36]. - The company’s ability to compete may be affected by the speed at which competitors obtain regulatory approvals for their medicines[36]. - The commercial success of PYRUKYND® will depend significantly on third-party payor coverage and reimbursement, which can vary widely among payors[129]. Employee and Workplace Culture - The company had 390 full-time employees and 2 part-time employees as of December 31, 2021, with 120 holding advanced degrees[88]. - 59% of the workforce were women, and 30% were ethnically diverse as of December 31, 2021[88]. - The company emphasizes flexibility, psychological safety, and deliberate development in its workplace culture[88]. Risks and Challenges - The company faces challenges in patient enrollment for clinical trials due to the ongoing COVID-19 pandemic, which may delay regulatory approvals[97]. - The company may experience increased development costs and potential abandonment of clinical trials if sufficient patient enrollment is not achieved[97]. - The company is exposed to risks of fraud or misconduct by third parties involved in its clinical trials and research activities[117]. Future Outlook - Future capital requirements will depend on various factors, including revenue from PYRUKYND® and the timing of regulatory approvals[109]. - The company anticipates prioritizing capital allocation towards accelerating development programs and pursuing complementary business opportunities[180]. - The company expects to incur significant commercialization expenses related to product sales, marketing, manufacturing, and distribution for PYRUKYND® if marketing approval is obtained[186].

Oncology Business Sale - The company is selling its oncology business to Servier for $1.8 billion in cash, with potential additional payments of $200 million upon FDA approval of vorasidenib[11]. - The oncology business sale is expected to be completed by the end of Q1 or beginning of Q2 2021, subject to regulatory approvals[12]. - The transaction is subject to stockholder approval and regulatory approvals, which may delay or prevent completion[134]. - The anticipated sale of the oncology business to Servier is expected to provide sufficient capital to fund operations through major catalysts and achieve cash-flow positivity without the need for additional equity[142]. - The oncology business sale will result in a smaller, less diversified company, increasing susceptibility to market fluctuations related to GDDs[198]. Focus on Genetically Defined Diseases (GDDs) - The company plans to focus on genetically defined diseases (GDDs) post-sale, which may increase susceptibility to market fluctuations due to reduced diversification[12]. - The lead product candidate in the GDD portfolio, mitapivat, is being evaluated for the treatment of pyruvate kinase deficiency, thalassemia, and sickle cell disease[16]. - The company aims to advance at least five internally discovered molecules in clinical development across ten indications[17]. - The company is developing small molecule therapies for genetically defined diseases (GDDs), with a focus on conditions that have significant unmet medical needs and potential for reversible damage[25]. - The company’s approach to GDDs includes developing mechanistically specific small molecules with potential disease-modifying effects rather than palliative care[25]. Clinical Development and Trials - The company expects to submit IND applications every 12-24 months to maintain a robust research pipeline[17]. - The company aims to progress drug candidates into phase 1 clinical trials by selecting patients based on specific biomarkers, enhancing the probability of success in drug development[26]. - Ongoing clinical trials for ivosidenib include a phase 3 trial combining it with VIDAZA® in newly diagnosed AML patients, which is currently enrolling[37]. - The ClarIDHy phase 3 trial for ivosidenib in cholangiocarcinoma has completed enrollment, with plans to file an sNDA with the FDA in Q1 2021[38]. - The DRIVE PK trial for mitapivat has completed enrollment, focusing on adult, transfusion-independent patients with PK deficiency[48]. Financial Performance - The company incurred net losses of $327.4 million, $411.5 million, and $346.0 million for the years ended December 31, 2020, 2019, and 2018, respectively, with an accumulated deficit of $1,843.5 million as of December 31, 2020[141]. - Total revenue for 2020 was $203.196 million, an increase from $117.912 million in 2019[194]. - Total cost and expenses for 2020 were $519.345 million, compared to $544.245 million in 2019[194]. - Net loss for 2020 was $327.370 million, down from a net loss of $411.472 million in 2019[194]. - Cash, cash equivalents, and marketable securities at year-end 2020 totaled $670.537 million, down from $717.806 million in 2019[194]. Regulatory Environment - The approval process for new drugs in the U.S. requires substantial time and financial resources, including preclinical testing and submission of a New Drug Application (NDA)[73]. - The FDA requires a 30-day waiting period after filing an Investigational New Drug (IND) application before clinical trials can commence, allowing for review of potential health risks to human subjects[76]. - The FDA may require the development of Risk Evaluation and Mitigation Strategies (REMS) as a condition of NDA approval to ensure product benefits outweigh potential risks[82]. - The FDA has established designations such as Fast Track, Breakthrough Therapy, and Priority Review to expedite the review of products addressing serious medical needs, potentially reducing review times from 10 months to 6 months[83]. - The FDA conducts pre-approval inspections of manufacturing facilities and clinical sites to ensure compliance with cGMP and GCP before approving an NDA[81]. Market Competition - The pharmaceutical and biotechnology industries are characterized by intense competition, with major competitors including AbbVie, Novartis, and Pfizer[67]. - The competitive landscape includes a variety of therapies for hematologic malignancies and genetically defined diseases, with many competitors having greater financial resources[67]. - The company faces competition from both established therapies and new medicines in development, which may provide significant competition for its product candidates[68]. - Competition from major pharmaceutical and biotechnology companies poses a risk, as they may develop products more effectively or rapidly than the company[152]. - The company may face challenges in achieving market acceptance for its products, which is essential for generating significant revenue and profitability[151]. Employee and Operational Considerations - The company has implemented measures to ensure employee safety during the COVID-19 pandemic, including health screenings and remote work arrangements[130]. - The company emphasizes flexibility, psychological safety, and deliberate development in its employee experience strategy[129]. - The company has established a competitive compensation and benefits package to incentivize strong performance[129]. - The company is in the process of selling its oncology business to Servier for $1.8 billion in cash, with potential additional payments of $200 million and royalties of 5% and 15% on U.S. net sales of TIBSOVO® and vorasidenib, respectively[198]. - The company is committed to complying with both U.S. and EU regulatory requirements for product approvals, ensuring alignment with international standards[109].

Table of Contents Title of each class Trading symbol(s) Name of each exchange on which registered Common Stock, Par Value $0.001 per share AGIO Nasdaq Global Select Market UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2020 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file ...

Table of Contents Title of each class Trading symbol(s) Name of each exchange on which registered Common Stock, Par Value $0.001 per share AGIO Nasdaq Global Select Market UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file numb ...