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Q3 2026 Financial Results and Business Highlights Conference call for investors and analysts 05 November 2026
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2 Forward Looking Statements This presentation and various remarks we make during this presentation 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 PYRUKYND® (mitapivat), AQVESME® (mitapivat), cevidoplenib, AG- 236, and AG-181; Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including mitapivat, cevidoplenib, AG-236 and AG-181; Agios’ expectations for the review of marketing applications for mitapivat by regulatory agencies, including the FDA; Agios’ strategic vision and goals; 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. 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, 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 presentation 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 impact of pandemics or other public health emergencies 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 current or future approved products, and launching, marketing and selling current or 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; 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 key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236 and cevidoplenib, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; 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 presentation 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, except as required by law.
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3 Q3 2026 earnings call agenda 1 Introduction Morgan Sanford, VP , Investor Relations 2 CEO Opening Remarks Brian Goff, Chief Executive Officer 3 Financial Results Cecilia Jones, Chief Financial Officer 4 Commercial Highlights Tsveta Milanova, Chief Commercial Officer 5 R&D Highlights Sarah Gheuens, M.D., Ph.D., Chief Medical Officer, Head of R&D 6 CEO Closing Remarks and Q&A
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4 CEO Opening Remarks Brian Goff, Chief Executive Officer
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51. for mitapivat product revenues. 2. As of September 30, 2026. Q3 2026 – commercial execution delivers record quarter1 Strong conviction in mitapivat sickle cell disease benefit-risk profile; PDUFA February 1, 2027; launch-ready Q3 net revenue surpassed full year 2025 Record quarter $907M Cash, cash equivalents and marketable securities2 $55.4M Total net revenue, increased 4.3x compared to Q3 2025
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6FDA=U.S. Food and Drug Administration; HCI=hepatocellular injury; OLE=open-label extension; PDUFA= Prescription Drug User Fee Act; REMS=Risk Evaluation and Mitigation Strategy. Confident in mitapivat approval in sickle cell disease February 1, 2027 New PDUFA goal date (original PDUFA goal date November 1, 2026) October 28, 2026 FDA classified the response as a major amendment (3-month extension) October 19, 2026 Agios responded, including ~9 months additional safety data from OLE periods October 9, 2026 FDA requested information to evaluate whether REMS is necessary Ongoing labeling discussions with FDA; launch-ready in sickle cell disease Overview of recent FDA engagement Why we remain confident Benefit-risk unchanged • No HCI cases similar in pattern or severity to what was observed in thalassemia clinical trials • Reaffirmed with ~9 months of additional OLE safety data Launch-ready Field, medical, market access and patient support teams trained and in place
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7 1. Assumes mitapivat launch in sickle cell disease in 2027 and does not include potential business development; Profitability based on Non-GAAP Net Income, excluding the following structural line items: share-based compensation expense, depreciation and asset amortization/impairments, acquisition-related income or expenses, restructuring charges. Mitapivat is approved for thalassemia under brand name PYRUKYND in Europe, Saudi Arabia and United Arab Emirates and approved under brand name AQVESME in the U.S. EU=European Union; ITP = immune thrombocytopenia; KSA=Kingdom of Saudi Arabia; PDUFA = Prescription Drug User Fee Act; PK=pyruvate kinase; SYKi=spleen tyrosine kinase inhibitor; TMPRSS6i=transmembrane serine protease 6 inhibitor; UAE= United Arab Emirates; UK=United Kingdom; US = United States. Sharpening our focus to drive the next phase of growth Maximize the mitapivat franchise Advance a focused rare hematology pipeline PK deficiency PYRUKYND® Approved U.S., EU, UK Thalassemia AQVESME®/ PYRUKYND Approved U.S., EU, KSA, UAE Sickle cell disease mitapivat FDA review ongoing Filed in KSA in Q2 2026 Right-sizing our operating model and capital allocation strategy >35% reduction in R&D headcount (>100 roles) in 2026 Focused clinical pipeline Advancing rare hematology assets with de-risked mechanisms and regulatory path Unlocking value from non-core assets Potential strategic optionality for AG-181 and vorasidenib royalty monetization Targeting non-GAAP profitability in 2028, driven by revenue growth and cost discipline1 Polycythemia vera AG-236 (TMPRSS6i) Phase 2/3 Planned H2 2026 ITP Cevidoplenib (SYKi) Phase 3 Planned H1 2028
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8 Financial Results Cecilia Jones, Chief Financial Officer
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9 Q3 2026 financial results Statement of Operations Q3 2026 ($M) Q3 2025 ($M) Mitapivat Net Revenue $55.4 $12.9 U.S. Net Revenue $48.7 $12.3 Ex-U.S. Net Revenue $6.6 $0.6 Cost of Sales $2.5 $1.7 Research & Development Expense $73.5 $86.8 Selling, General & Administrative Expense $56.5 $41.3 Net (Loss) Income ($65.0) ($103.4) Balance Sheet Q3 2026 Q4 2025 Cash, Cash Equivalents and Marketable Securities $907.0M $1.2B
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10 Commercial Highlights Tsveta Milanova, Chief Commercial Officer
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11QoQ=quarter over quarter; U.S.=United States; WW=worldwide. Quarterly results may vary with ordering patterns, inventory and gross-to-net (GtN). Q3 2026 – thalassemia launch drives record revenue Mitapivat WW Total Net Revenues – Quarterly ($M) $12.3 $16.0 $18.9 $40.9 $48.7 $0.6 $4.0 $1.9 $3.8 $6.6 Q3 2025 Q4 2025 Q1 2026 Q2 2026 Q3 2026 U.S. ex-U.S. $12.9M $20.0M $20.8M $44.7M $55.4M Key Q3 2026 dynamics • $55.4M Total WW Net Revenues ― +4.3x compared to Q3 2025 • $48.7M U.S. Net Revenues ― +20% QoQ growth, driven by AQVESME demand across broad thalassemia population • $6.6M ex-U.S. Net Revenues ― +74% QoQ growth, driven by early access programs in Europe following Q2 thalassemia approval
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12 1. Prescriptions from REMS-certified HCPs with completed Agios start forms, counted in the quarter the form is completed; consistent with externally reported metric. 2. ENERGIZE open-label extension in NTD thalassemia (EHA 2026, Oral S296). Hb response: ≥1.0 g/dL increase from baseline in average Hb over any 2 consecutive OLE visits. EHA=European Hematology Association; Hb=hemoglobin; HCP=health care provider; NTD=non-transfusion-dependent; OLE=open-label extension; REMS=Risk Evaluation and Management Strategy AQVESME – broadening demand and persistency support continued revenue growth Field focus - continued demand generation from community prescribers, growing transfusion-dependent adoption and deeper expansion into non-transfusion dependent segment AQVESME demand three quarters into U.S. launch 177 prescriptions with completed Agios Start Forms (ASFs)1 in Q3 619 cumulative prescriptions with completed ASFs1 since launch 48 prescriptions with in-process ASFs as of Q3 Strong, early persistency building a durable patient base of patients remain on AQVESME after 6 months of treatment ~75% Early persistency is reinforced by long-term data presented at EHA 2026 • ~1/3 of prior non-responders responded with longer treatment² • 43.6 weeks mean Hb response duration, up from 17.9 wks²
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13 August 2026 Launched additional targeted omnichannel activation Multilingual campaign Addressing diverse needs of the multicultural community Increased Engagement Growing patient engagement across AQVESME DTC digital channels +65% increase in high value actions on DTC website following Level Up Campaign launch Source: Agios data on file. DTC = direct to consumer.
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AQVESME – strong reception from thalassemia community 14Market Research source: Agios data on file, research conducted September 2026. Market research: Physician experience supports broad use across TD and NTD thalassemia …This patient has had an excellent response… he’s trying to get into an exercise routine…he can get through a day of work…it’s clear he feels a real difference - Treating physician on NTDT patient Over six months, tracking consistent Hb increases from 8.1g/dL to 9.1g/dL – gives me confidence about the role of sustained treatment with AQVESME - Treating physician on NTDT patient …no longer needs top-off transfusions before traveling…also very pleased that her ferritin has decreased below 500ng/mL - Treating physician on TDT patient • Reduction in transfusion burden and transfusion visits • Convenient route of administration (oral) • Improvement in quality of life • Increase in hemoglobin levels • Convenient route of administration (oral) • Reduction in fatigue, improvement in quality of life Non-transfusion dependent (NTD)∙ Top drivers of use Transfusion dependent (TD)∙ Top drivers of use
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151. Payne AB, et al. Trends in sickle cell disease-related mortality in the United States, 1979-2017. Annals of Emergency Medicine. 2020; 76 (3S):S28-S36. HCP=health care physician; PDUFA=Prescription Drug User Fee Act. Sickle cell disease – launch-ready ahead of PDUFA date ~75K diagnosed patients 16 years and older ~25K initial launch target focused on actively engaged patients in need of therapy Focused launch opportunity to prioritize speed of adoption Disease education underway and ongoing Hemolysis as a root cause Sickle cell disease launch leverages thalassemia infrastructure in >6x larger addressable launch population (~25k vs ~4k) Dedicated field, medical and patient-support teams hired and trained Established manufacturing and supply chain – staged for day-one availability Priority HCPs targets mapped to focused launch patient population Chronic hemolysis underlying disease driver Progressive organ injury kidney ∙ heart ∙ brain Premature mortality median 43 years old in U.S.1
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16 R&D Highlights Sarah Gheuens, M.D., Ph.D., Chief Medical Officer, Head of R&D
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17 1. Defined as completion of double-blind randomized portion of the trial. EU=European Union; FDA=U.S. Food and Drug Administration; KSA=Kingdom of Saudi Arabia; PAH=phenylalanine hydroxylase; PK=pyruvate kinase; siRNA=small interfering RNA; sNDA=supplemental new drug application; sNDA=supplemental new drug application; SYKi=spleen tyrosine kinase inhibitor; TMPRSS6=transmembrane protease serine 6; UAE=United Arab Emirates; UK=United Kingdom. Focused pipeline advancing leadership in rare hematology PRECLINICAL EARLY-STAGE LATE-STAGE REGULATORY SUBMISSION APPROVAL PhenylketonuriaAG-181 PAH stabilizer Phase 1b ongoing Polycythemia VeraAG-236 siRNA TMPRSS6 Planned Phase 2/3 initiation H2 2026 Mitapivat First-in-class PK activator PYRUKYND® PK Deficiency Sickle Cell Disease Approved U.S., EU, UK Phase 3 completed1 ACTIVATE-Kids/KidsT sNDA under review by FDA; REIGNITE confirmatory trial ongoing; Filed in KSA AQVESME® (U.S.) PYRUKYND® (KSA, UAE, EU) Thalassemia Approved U.S., KSA, UAE, EU Phase 3 ENERGIZE-Kids/KidsT ongoing Immune Thrombocytopenia Cevidoplenib Next-gen SYKi Phase 3 to initiate H1 2028 Continued enrollment in REIGNITE Phase 3 confirmatory trial for mitapivat in sickle cell disease
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181. OLE Hb improvement: increase of ≥1.0 g/dL from baseline in average Hb during any two consecutive OLE visits. Source: ASH 2026 abstracts. eGFR=estimated glomerular filtration rate; Hb=hemoglobin; LVMI=left ventricular mass index; OLE=open-label extension; PKM2=pyruvate kinase muscle isozyme 2; SCD=sickle cell disease. Mitapivat at ASH 2026 – durable Hb benefit and organ improvements targeting key drivers of SCD mortality Durable Hb response and emerging organ data strengthen mitapivat’s sickle cell disease profile RISE UP Phase 3 Open-label extension data Kidney effect independent of Hb response Suggests PKM2-mediated effect beyond anemia correction Heart remodels favorably in Hb responders Left atrial volume also reduced; supports disease-modifying potential Δ eGFR at Wk 52 Mitapivat PBO Hyperfiltrators −14.7 −4.9 Normofiltrators −5.0 −0.6 Mean Δ LVMI, Wk 52 (g/m²) Hb resp. −5.9 Non-resp. +5.8 Placebo +4.6 Mitapivat beyond Hb – emerging kidney and cardiac benefits 115 weeks – longest ongoing Hb response 62.7% achieved OLE Hb improvement1 39.7% of initial non-responders improved Hb benefit lasts – and deepens – with continued mitapivat treatment
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19 1. Hepcidin was not measured after Day 57. 2. Agios data on file 2026 includes feedback from 50 KOLs across U.S., Europe and Asia. Values shown are mean change from baseline from the AG-236 Phase 1 SAD study in healthy participants (NCT07075640; AG-236 n=6 per dose, placebo n=6). Source: ASH 2026 abstract. HV=healthy volunteer; KOL=key opinion leader; PV=polycythemia vera; Q6M=every six months; SD=standard deviation; TSAT=transferrin saturation AG-236 at ASH 2026 – Phase 1 HV data support Phase 2/3 initiation in PV in H2 2026 Mean (SD) change from baseline AG-236 Placebo Durability 1.0 mg/kg 3.0 mg/kg 9.0 mg/kg Hepcidin, µg/L (Day 29) ↑ +18.9 (12.8) ↑ +10.3 (21.8) ↑ +24.1 (11.1) ↓ −1.3 (3.7) Consistent through Day 57 TSAT, % (Day 29) ↓ −18.0 (5.5) ↓ −20.8 (8.4) ↓ −15.3 (5.6) ↓ −6.7 (6.5) Sustained through Month 6 Hematocrit, % (Day 57) ↓ −1.3 (3.0) ↓ −3.5 (2.7) ↓ −2.9 (2.9) ↑ +0.9 (1.8) Sustained through Month 6 Global KOL feedback confirms Q6M control as potential paradigm shift in polycythemia vera2 Full data through month 6 presented at upcoming 2026 American Society of Hematology (ASH) Meeting Effects of AG-236 on serum iron, TSAT, hemoglobin and hematocrit sustained post-dose through Month 61
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20PKU = phenylketonuria; PAH = phenylalanine hydroxylase; Phe = phenylalanine; BID = twice daily; HV = healthy volunteer. AG-181 – preclinical and healthy volunteer data support novel PAH stabilizer mechanism in PKU Phase 1b proof-of-mechanism data in PKU patients expected H2 2026 Preclinical classical/severe PKU (PAHR408W/R408W) mouse model Phase 1 HV data – presented at SSIEM 2026 Exposure Human exposures at Phase 1b doses comfortably within the range of efficacious mouse exposures Safety & tolerability No serious or Grade ≥3 AEs and no discontinuations PK profile Supports BID dosing in ongoing Phase 1b in PKU patients -24 0 0 500 1000 1500 2000 2500 4 8 12 16 20 24 28 32 36 R408W / R408W Hours Post Dose Blood Phe (M) Vehicle group AG-181 30 mg/kg AG-181 100 mg/kg AG-181 300 mg/kg Significant dose responsive reduction in blood Phe levels Achieves clinical target Phe blood level <360 µM at 300 mg/kg without diet modification
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21 CEO Closing Remarks Brian Goff, Chief Executive Officer
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22EU=European Union; KSA=Kingdom of Saudi Arabia; PAH=phenylalanine hydroxylase; PDUFA=Prescription Drug User Fee Act; PKU=phenylketonuria; sNDA=supplemental New Drug Application; SYK=spleen tyrosine kinase; TMPRSS6i=transmembrane serine protease 6 inhibitor; UAE=United Arab Emirates; U.S.=United States. Agios – focused rare hematology company entering next phase of growth First medicine approved for broad thalassemia population Strong anti-hemolytic profile with emerging organ-health data Next-gen SYK inhibitor, improved tolerability may drive durability TMPRSS6i designed for sustained hepcidin control, extended dosing PAH enzyme stabilizer, potential for durable Phe control AQVESME /PYRUKYND® approved U.S., EU, KSA, UAE Cevidoplenib Phase 3 planned for H1 2028 AG-236 Phase 2/3 trial initiating in H2 2026 AG-181 proof-of-mechanism data in PKU patients H2 2026 Thalassemia Sickle Cell Disease Immune Thrombocytopenia Polycythemia Vera Phenylketonuria Focused rare hematology pipeline Strategic optionality – broader rare disease Record Q3 revenue driven by thalassemia – launch-ready in sickle-cell disease – well capitalized to execute Mitapivat sNDA – PDUFA Feb. 1, 2027; in labeling discussions; launch-ready
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23 Q&A Session
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24 Appendix
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25Q6M=every six months; Q26W=every 26 weeks; Q13W=every 13 weeks. APPENDIX – AG-236 Phase 2/3 trial is operationally seamless Advancing AG-236 through operationally seamless Phase 2/3 strategy to optimize therapeutic window and support rapid progression toward registration Addressing broad target population Includes patients requiring frequent phlebotomy and those on stable cytoreductive therapy Efficient registrational strategy Operationally seamless Phase 2/3 design AG-236 – potential chronic disease differentiation Sustained hepcidin and iron regulation | Potential for Q6M dosing | No titration required
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26 Preclinical: mitapivat (1200 ppm chow) vs standard chow in hemin-challenged Berkeley SCD mice; fibrosis score 0.17 vs 1.17; inner medulla iron deposition score 0.75 vs 1.70 (male mice). ESTIMATE: exploratory analysis of n=5 patients with paired urine samples, baseline vs 1–2 years, markers normalized to urinary creatinine; NAG/creatinine increased 40.2%. 1. Nguyen T, et al. Blood. 2024;144(Suppl 1):1107. 2. Kuppens GZL, et al. Haematologica. 2026;111(8):2792-2796. eGFR = estimated glomerular filtration rate; IST = investigator-sponsored trial; KIM-1 = kidney injury molecule-1; NAG = N-acetyl-β-D-glucosaminidase; SCD = sickle cell disease. APPENDIX – Existing published data supporting the role of PKM2 activation on measures related to organ health Preclinical – SCD nephropathy mouse model¹ Mitapivat in hemin-challenged Berkeley SCD mice ↓85% interstitial fibrosis score (p≤0.002) ↓56% inner medulla iron deposition (p=0.014) Fewer protein casts and lower nephropathy severity vs control¹ ESTIMATE IST – 3-year renal outcomes² Phase 2 open-label study in patients with SCD ↓50.7% nephrin/ creatinine ↓99.8% urinary Hb/ creatinine ↓92.0% KIM-1/ creatinine eGFR >90 mL/min/1.73m² maintained in all patients² First human renal biomarker findings directionally consistent with preclinical kidney models
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27 APPENDIX – AG-181 preclinical data PAH = phenylalanine hydroxylase; Phe = phenylalanine; Tyr = tyrosine; BH4 = tetrahydrobiopterin; WT = wild type. Proprietary R408W model recapitulates severe PKU AG-181 stabilizes PAH-R408W protein in cells AG-181 increases Phe-to-Tyr activity in cells • 95% reduction in liver PAH protein vs. WT, confirming the destabilizing effect of R408W • Blood and brain Phe >20x WT, similar to untreated R408W patients • Lighter coat color: high Phe interferes with Tyr → melanin Untreated AG-181 (10 µM) Fold increase in PAH-R408W protein vs. untreated Phenylalanine hydroxylase (PAH) gene