Agios Pharmaceuticals, Inc. · NASDAQ:AGIO
Agios Pharmaceuticals — Investor Presentation (January 2024)
22 slides from Agios Pharmaceuticals's investor presentation, January 2024
Slide 1: Sickle Cell Disease Education and Therapeutic Management
Sickle Cell Disease Education and Therapeutic Management SCD-ALL-0080 / January 2024
Slide 2: Table of Contents
Table of Contents SCD Overview 3 Pathophysiology of SCD 6 Patient Impact 11 Unmet Needs in SCD and Emerging Treatments 17 Summary 21 SCD, sickle cell disease. SCD-ALL-0080 / January 2024
Slide 3: SCD Overview
SCD Overview SCD, sickle cell disease. SCD-ALL-0080 / January 2024
Slide 4: Overview
Overview Morphologic changes Sickle cell disease1,2 HbS polymerization1 (e.g., RBC sickling)1,3 Group of inherited disorders • Drives a cascade of pathologic • Impair normal biorheology • Characterized by mutations in processes involving abnormal • Drives the downstream the β-globin gene, resulting
Slide 5: SCD Is Among the Most Common Inherited Conditions Globally
SCD Is Among the Most Common Inherited Conditions Globally1 ▪ SCD impacts ~100,000 individuals in the ▪ SCD incidence shows a wide range4,*: United States and >7,000,000 individuals ▪ 0.07 per 1000 in nonendemic areas globally1,2 ▪ 10.68 per 1000 in African regions ▪ It is more common in people desc
Slide 6: Pathophysiology of SCD
Pathophysiology of SCD SCD, sickle cell disease. SCD-ALL-0080 / January 2024
Slide 7: Key Pathophysiological Processes in SCD
Key Pathophysiological Processes in SCD ▪ HbS mutation in β-globin chains results in HbS polymerization1,3,4 multiple synergistic pathological processes1,2: Hemolysis ⇀ ⇀ Hb Sickling HbS ↽ ↽ polymer a. HbS polymerization bundles β6 triplet codon GAG ⟶ GTG HbS polymers are rigid and distort RBCs, cau
Slide 8: Polymerization of Deoxygenated HbS Tetramers Leads to RBC Sickling
Polymerization of Deoxygenated HbS Tetramers Leads to RBC Sickling1,2 ▪ The substitution of glutamic acid with valine at the 6th position of the β-globulin polypeptide chain (dbSNP identifier Rs334) drives hemoglobin polymerization in SCD2,3 GAG is replaced GTG hydrophilic Glu by hydrophobic Val G G
Slide 9: Intravascular Hemolysis Contributes to Vasculopathy, Endothelial Dysfunction, and Vaso-Occlusion in SCD
Intravascular Hemolysis Contributes to Vasculopathy, Endothelial Dysfunction, and Vaso-Occlusion in SCD Intravascular hemolysis: Contributes to chronic Vaso-occlusion: Adhesion proteins on the activated endothelium interact vasculopathy, platelet activation, and pulmonary with sickled RBCs, neutroph
Slide 10: Hemolysis Also Activates Danger-Associated Molecular Pattern Signaling and Sterile Inflammation
Hemolysis Also Activates Danger-Associated Molecular Pattern Signaling and Sterile Inflammation Sterile inflammation: Pathogen-free inflammation mediated by free heme and DAMPs 1,2 DAMPs (heme, ATP, HMGB1)1,3,4 ▪ Heme activates TLR4 on endothelial cells and monocyte/ Endothelium3 Macrophages3 Neutro
Slide 11: Patient Impact
Patient Impact SCD-ALL-0080 / January 2024
Slide 12: SCD Is Associated With Increased Mortality
SCD Is Associated With Increased Mortality SCD Has an Annual Global Mortality Burden of 376,000 Individuals All-age total sickle disease mortality rate, males and females, 20211 In the United States, SCD continues to be a source of early mortality among African Americans2 75 40 Reduced overall life
Slide 13: SCD-Associated Vaso-Occlusion Underlies the Phenotypic Features of SCD
SCD-Associated Vaso-Occlusion Underlies the Phenotypic Features of SCD Acute pain Acute chest syndrome Vaso-occlusion Hyposplenism Sickling Osteonecrosis Vaso-occlusion Nephropathy Inflammation Increased VCAM-1 Hypercoagulability and adhesion molecule expression Even after reperfusion, vasculopathy
Slide 14: SCD Is Linked With Pain, Vaso-Occlusion, and Other Comorbidities
SCD Is Linked With Pain, Vaso-Occlusion, and Other Comorbidities In a retrospective longitudinal cohort study of >7500 individuals with SCD, the most prevalent conditions by age were reported as1,*: <18 and 18 to 45 years: 46 to 64 years: Older adults vs. <18 years: Vaso-occlusive pain and Infection
Slide 15: SCD Has a Significant Impact on Patient QOL
SCD Has a Significant Impact on Patient QOL SWAY: A multicountry, cross-sectional survey assessing the impact of SCD on the daily lives of 2145 patients between April and October 20191 ▪ SCD patients reported disruptions in both Emotional and Overall Function domains SCD Patients Reporting Disrupted
Slide 16: Economic Burden in SCD Goes Beyond Patient OOP Costs
Economic Burden in SCD Goes Beyond Patient OOP Costs A retrospective observational study of EHR claims A meta-analysis from 2005 through 2015 estimated the annual and systemic incremental economic burden of SCD at1,*: literature search of publications $10,079 per patient: between 1997 and Outpatient
Slide 17: Unmet Needs in SCD and Emerging Treatments
Unmet Needs in SCD and Emerging Treatments SCD, sickle cell disease. SCD-ALL-0080 / January 2024
Slide 18: SCD Diagnosis May Be Missed in Individuals Not Evaluated by Newborn Screening
SCD Diagnosis May Be Missed in Individuals Not Evaluated by Newborn Screening Insights and Considerations on Patterns of SCD Diagnosis Widespread adoption of newborn screening in the United States and most of Europe allows for the early detection of SCD1-3 Globally, lack of universal newborn screeni
Slide 19: No Approved Disease Modifying SCD Treatment Both Increases Hb Levels And Reduces VOEs
No Approved Disease Modifying SCD Treatment Both Increases Hb Levels And Reduces VOEs1 SCD Treatments Treatment Target and MOA Disease Modifying Transfusions and Transfusion6 • Reduction in HbS-containing RBCs pharmacotherapies2-5 Gene Therapy • Increased HbF synthesis and Restoring faulty or missin
Slide 20: Emerging SCD Treatments Target Various Signaling Pathways
Emerging SCD Treatments Target Various Signaling Pathways Therapeutic Strategy: Therapeutic Strategy: Therapeutic Strategy: Inhibition of HbS Target downstream PK activation1 polymerization2-5 pathways1,6,7 • ATP increase improves RBC • Gene modification to reverse • Inhibition of endothelial cell h
Slide 21: Summary
Summary SCD-ALL-0080 / January 2024
Slide 22: Summary
Summary SCD is a group of inherited disorders In SCD, HbS polymerization drives a cascade characterized by mutations in the β-globin of pathologic processes involving abnormal gene; SCD impacts ~100,000 individuals in RBC function, resulting in endothelial dysfunction, the United States, and >7 mill
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