Slide 1: Q2 2023 Financial Results
Q2 2023 Financial Results August 3, 2023 1
Slide 2: Agios conference call participants
Agios conference call participants TOPIC PARTICIPANT Introduction Chris Taylor, Investor Relations and CorpComm Business Update Brian Goff, Chief Executive Officer Sarah Gheuens, M.D., Ph.D., Chief Medical Officer, Research & Development Update Head of Research and Development Commercial Update Tsve
Slide 3: Forward-looking statements
Forward-looking statements This presentation and various remarks we make during this presentation contain 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®
Slide 4: Opening Remarks
>< agios Opening Remarks
Slide 5: Q2 2023 highlights
Q2 2023 highlights Pipeline updates Corporate updates • Completed enrollment of Phase 3 ENERGIZE and • Expanded pipeline through license ENERGIZE-T clinical trials of mitapivat in agreement with Alnylam for novel thalassemia; on track for data readouts in 2024 siRNA for potential treatment of polycy
Slide 6: Preclinical siRNA targeting TMPRSS6 is a potential disease-modifying treatment for PV
Preclinical siRNA targeting TMPRSS6 is a potential disease-modifying treatment for Polycythemia Vera (PV) Agreement combines Agios’ scientific expertise and capabilities in rare hematological diseases with Alnylam’s industry-leading siRNA platform PV is a rare hematological disease with no disease-m
Slide 7: Clinical and regulatory milestones targeted in 2023
Clinical and regulatory milestones targeted in 2023 lay the foundation for transformational data readouts NEW 2023 Pediatric PK Deficiency MILESTONE Thalassemia PYRUKYND® Lower-Risk MDS PYRUKYND® Enroll at least half of patients in the AG-946 (Novel PK Activator) Lower-Risk MDS Complete enrollment o
Slide 8: Clinical
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Slide 9: RISE UP Phase 2: primary efficacy endpoint achieved for both doses
RISE UP Phase 2: primary efficacy endpoint achieved for both doses The Phase 2 portion of the global RISE UP study of mitapivat in sickle cell disease met its primary endpoint of hemoglobin response for both 50 mg BID and 100 mg BID • RISE UP Phase 2 study enrolled 79 patients, with 27 patients on p
Slide 10: RISE UP Phase 3 Study: first patient enrolled expected in Q4 2023
RISE UP Phase 3 Study: first patient enrolled expected in Q4 2023 Phase 3 primary endpoints (1): Hb response, defined as a ≥ 1.0 g/dL increase in average Hb concentration over Weeks 24–52 compared with baseline, and annualized rate of SCPCs Key inclusion criteria Key exclusion criteria • ≥ 16 years
Slide 11: Building a diverse pipeline leveraging our expertise in cellular metabolism
Building a diverse pipeline leveraging our expertise in cellular metabolism EARLY-STAGE LATE-STAGE REGULATORY RESEARCH APPROVAL CLINICAL DEVELOPMENT CLINICAL DEVELOPMENT SUBMISSION Pyruvate Kinase Deficiency US, EU, GB ACTIVATE Kids Enrollment ongoing in both ACTIVATE KidsT Phase 3 studies α- and β-
Slide 12: Strengthening therapeutic breadth in rare disease
Strengthening therapeutic breadth in rare disease Pyruvate kinase deficiency Polycythemia Thalassemia Vera RARE HEMATOLOGICAL DISORDERS Sickle cell Myelodysplastic disease syndrome 12
Slide 13: Polycythemia Vera and TMPRSS6 siRNA mechanism of action
Polycythemia Vera and TMPRSS6 siRNA mechanism of action 1 2 3 Hepcidin is a master regulator PV causes iron deficiency in the Hepcidin is negatively regulated in hepatocytes of iron metabolism. absence of anemia by the membrane protease TMPRSS6 Increased Hepcidin Erythropoietic production activity H
Slide 14: Commercial
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Slide 15: PYRUKYND Q2 2023 performance metrics highlight continued progress
PYRUKYND® Q2 2023 performance metrics highlight continued progress $6.7M net U.S. sales of PYRUKYND® a 20% increase over Q1 2023 147 unique patients completed PYRUKYND® prescription enrollment forms, a 16% increase over Q1 2023 99 patients on PYRUKYND®, which includes new prescriptions and those con
Slide 16: Implementing a comprehensive commercial strategy across the patient journey
Implementing a comprehensive commercial strategy that addresses each stage of the patient journey Awareness and Access and Adherence and Education Initiation Persistency Increase disease Accelerate access by Support adherence awareness and reducing the time and maintain educate on available between
Slide 17: PK activation franchise positioned for meaningful expansion
PK activation franchise positioned for meaningful expansion, with near-term opportunity in thalassemia PYRUKYND® is the first and only disease- modifying treatment approved for adults with PK deficiency ADDITIONAL OPPORTUNITIES Sickle cell disease FOR THE FRANCHISE WITH NOVEL Potential U.S. approval
Slide 18: Agios aims to deliver the first therapy approved for all thalassemia subtypes
Agios aims to deliver the first therapy approved for all thalassemia subtypes Thalassemia (~8k patients US) Alpha Thalassemia Beta Thalassemia Non-Transfusion Transfusion Non-Transfusion Transfusion Dependent Dependent Dependent Dependent Alpha Thalassemia Alpha Thalassemia Beta Thalassemia Beta Tha
Slide 19: Thalassemia and SCD markets concentrated in select geographies
Thalassemia and SCD markets concentrated in select geographies Thalassemia Patients Sickle Cell Disease Patients ~150k PATIENTS ~102k PATIENTS ~70k PATIENTS ~34k PATIENTS ~13k ~8k PATIENTS PATIENTS U.S. EU5 GCC U.S. EU5 GCC GCC: Kingdom of Saudi Arabia, Oman, United Arab Emirates, Qatar, Bahrain, Ku
Slide 20: Financial
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Slide 21: Second quarter 2023 financial results
Second quarter 2023 financial results Three Months Ended Three Months Ended Statement of Operations 6/30/23 6/30/22 PYRUKYND® Net Revenue $6.7M $3.1M Cost of Sales $1.1M $0.4M Research & Development Expense $68.9M $74.5M Selling, General & Administrative Expense $30.4M $28.3M Gain on Sale of Oncolog
Slide 22: Closing Remarks
>< agios Closing Remarks
Slide 23: Potential for two additional PYRUKYND indications by 2026
Potential for two additional PYRUKYND® indications by 2026 2024 2025 2026 Thalassemia Phase 3 ENERGIZE (1H) and ENERGIZE-T Potential approval PYRUKYND® (2H) readouts Pediatric PK Phase 3 ACTIVATE- Deficiency kids and ACTIVATE- Potential approval kidsT readouts PYRUKYND® Sickle Cell Disease Potential
Slide 24: Q&A
Q&A 24
Slide 25: Appendix
>< agios Appendix
Slide 26: Mitapivat significantly increased hemoglobin response rate versus placebo
Treatment with mitapivat demonstrated a statistically significant increase in hemoglobin response rate compared to placebo Placebo Mitapivat 50 mg BID Mitapivat 100 mg BID N=27 N=26 N=26 Hemoglobin responders, n (%) 1 (3.7) 12 (46.2) 13 (50.0) Difference of response rate (Mitapivat-Placebo), % 42.5
Slide 27: Annualized rates of sickle cell pain crises lower in mitapivat arms
Annualized rates of sickle cell pain crises for patients in the mitapivat arms were lower compared to patients in the placebo arm CRC Adjudicated Data Negative Binomial Regression Model Placebo Mitapivat 50 mg BID Mitapivat 100 mg BID N=27 N=26 N=26 Annualized Rate of SCPC 1.71 0.83 0.51 95% CI (0.9
Slide 28: Two global Phase 3 trials of PYRUKYND in thalassemia
Two global, Phase 3, randomized controlled trials of PYRUKYND® in thalassemia encompass broad range of thalassemia patients N = 171 N = 240 2:1 randomization 2:1 randomization 100 mg BID Placebo BID 100 mg BID Placebo BID 24-week core period 48-week core period Open-label extension (up to 5 years) O
Slide 29: Mitapivat development program in pediatric PK deficiency
Mitapivat development program in pediatric PK deficiency to support potential label expansion to those under 18 Not Regularly Transfused PK Deficiency N=30 Regularly Transfused PK Deficiency N=45 Randomize 2:1 Randomize 2:1 Mitapivat Mitapivat Mitapivat Mitapivat OLE OLE placebo placebo 5 years plac
Slide 30: AG-946: Seamless Phase 2a proof-of-concept + Phase 2b trials
Novel PK activator AG-946: Seamless Phase 2a proof-of-concept + Phase 2b trials focused on establishing proof-of-concept and dose selection in LR-MDS Phase Open Label Phase 2a Double Blind, 1:1:1:1 Randomization 2b High N = 20 Open-Label dose Extension High dose AG-946 16 weeks Medium dose Open-Labe
Slide 31: Lead research program aimed to address phenylketonuria (PKU)
Lead research program aimed to address phenylketonuria (PKU) Normal Protein Diet PHENYLKETONURIA (PKU) A mixed diet provides your body Phe 1 • Rare, genetic disease with limited treatment options • Prevalence: total of ~35-40K patients in the U.S. and EU5 • Driven by deficiency of phenylalanine hydr