Agios Pharmaceuticals, Inc. · NASDAQ:AGIO
Agios Pharmaceuticals — Investor Day (May 2018)
152 slides from Agios Pharmaceuticals's investor day presentation, May 4, 2018
Slide 1: Opening Remarks
Opening Remarks David Schenkein, M.D., Chief Executive Officer Exhibit 99.2
Slide 2: 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 Agios’ plans, strategies and expect
Slide 3: Today's Agenda
Time Speaker 8:00 - 8:15 a.m. Opening Remarks – David Schenkein, M.D., Chief Executive Officer Research 8:15 - 9:00 a.m. Discovery Strategy & Research Portfolio – Scott Biller, Ph.D., Chief Scientific Officer & Kevin Marks, Ph.D., Senior Director, Head of Cancer Biology 9:00 - 9:20 a.m. Q&A Part 1 C
Slide 4: Driven By a Clear Vision and Values
Agios is passionately committed to applying our scientific leadership in the field of cellular metabolism to transform the lives of patients with cancer and rare genetic diseases. Driven By a Clear Vision and Values CANCER METABOLISM METABOLIC IMMUNO-ONCOLOGY RARE GENETIC DISEASES ADJACENT BIOLOGY S
Slide 5: Building One of the Next Great Pharmaceutical Companies
Building One of the Next Great Pharmaceutical Companies Biotech startups Initiated clinical trials One drug approved Two drugs approved Sustainable multiproduct companies
Slide 6: Agios' Scientific Platform Demonstrates Remarkable, Reproducible Productivity
Agios’ Scientific Platform Demonstrates Remarkable, Reproducible Productivity SCIENCE CULTURE DISCOVERY 400+ EMPLOYEES 1 VISION $50-60M INVESTED IN DRUG DISCOVERY ANNUALLY 40+ PEER-REVIEWED PUBLICATIONS IN 4 YEARS SINCE FIRST PATIENT DOSED 2 NDA ACCEPTED 3 ADDITIONAL COMPOUNDS IN CLINICAL DEVELOPMEN
Slide 7: Current Clinical Portfolio Has Potential to Benefit Large Number of Patients
Current Clinical Portfolio Has Potential to Benefit Large Number of Patients ACUTE MYELOID LEUKEMIA CHOLANGIO- CARCINOMA LOW GRADE GLIOMA MTAP-DELETED TUMORS ~10,000 IDHm Patients AML Opportunity ~$2B ~3,000 IDH1m Patients ~9,000 IDH1m Patients >100,000 MTAP Deletion Patients PYRUVATE KINASE DEFICIE
Slide 8: 2018 Key Milestones
2018 Key Milestones Secure approval and commercialize ivosidenib for IDH1m R/R AML in the U.S. Initiate AG-348 PK deficiency pivotal trial ACTIVATE-T; Initiate ACTIVATE Initiate AG-270 Phase 1 dose-escalation trial in MTAP-deleted cancers Initiate AG-348 Phase 2 proof-of-concept trial in thalassemia
Slide 9: 2018 Goals Set Stage for Building Long-Term Value
2018 Goals Set Stage for Building Long-Term Value Secure approval and commercialize ivosidenib for R/R AML in the U.S. Initiate Phase 3 frontline AML trial combining ivosidenib & enasidenib with 7+3 Initiate AG-348 PK deficiency pivotal trial (ACTIVATE-T) Initiate AG-270 Phase 1 dose-escalation tria
Slide 10: Our Pipeline
Our Pipeline CLINICAL PROGRAMS indication Drug discovery Early stage Clinical development Late stage clinical development APPROVED Primary commercial rights IDHIFA® Enasidenib (IDH2m Inhibitor) R/R AML Agios U.S. Co-promotion and Royalty Frontline AML Ivosidenib (IDH1m Inhibitor) R/R AML Frontline A
Slide 11: What You Will Hear and See Today
What You Will Hear and See Today Research engine poised to deliver next wave of development candidates Several new programs highlighted 9 programs currently in advanced drug discovery Robust clinical development plans in place across our early and late-stage programs Ready to launch our 2nd commerci
Slide 12: Discovery Strategy & Research Portfolio
Discovery Strategy & Research Portfolio Scott Biller, Ph.D., Chief Scientific Officer
Slide 13: Evolving the Agios Research Portfolio Into Adjacent Biologic Areas
Evolving the Agios Research Portfolio Into Adjacent Biologic Areas 2009 CANCER METABOLISM 2011 CANCER METABOLISM RARE GENETIC DISEASES 2016 CANCER METABOLISM METABOLIC IMMUNO-ONCOLOGY RARE GENETIC DISEASES Today ADJACENT BIOLOGY SPACE CANCER METABOLISM METABOLIC IMMUNO-ONCOLOGY RARE GENETIC DISEASES
Slide 14: Dysregulated Metabolism and Adjacent Areas of Biology
Dysregulated Metabolism and Adjacent Areas of Biology Agios Research Focus Rare Genetic Diseases Restore defective metabolic pathways in disease cells that cause rare genetic diseases of metabolism Cancer Metabolism Inhibit key enzymes in cancer cell specific metabolic pathways to disrupt tumor cell
Slide 15: Evolving our Technology Platform to a Systems Biology Approach
So Evolving our Technology Platform from our Historic Strength in Metabolism to a Cutting-Edge, Systems Biology Approach Metabolomics + Informatics + Modeling Multi-Omics + Imaging + Data Integration à New Knowledge Deep understanding of biology with a translational focus Single Cell RNA Sequencing
Slide 16: Precision Medicine Program Criteria
Precision Medicine Program Criteria Animal model target validation Genetic and metabolic biomarkers High confidence in druggability High Probability of Success for Agios Drug Discovery Patient selection strategy Robust chemical starting points Proof of therapeutic strategy in vivo
Slide 17: What Differentiates Agios Research Strategy?
What Differentiates Agios Research Strategy? First-in-Class Precision Medicines Internally Highly Integrated Deep Biological Interrogation Externally Hyper- Connected Early Translational Thinking Rapid Clinical Proof of Concept
Slide 18: Agios Preclinical Pipeline
Agios Preclinical Pipeline Program Target Discovery Target Validation Drug Discovery Drug Candidate Oncology Rare Genetic Diseases Metabolic Immuno-Oncology (Celgene Collaboration) Non-Metabolic Target Metabolic Target Metabolic and Non-Metabolic Targets Celgene Collaboration MAT2A Follow-Ons Heme L
Slide 19: Agios Areas of Research Focus
Agios Areas of Research Focus Rare Genetic Diseases Restore defective metabolic pathways in disease cells that cause rare genetic diseases of metabolism Cancer Metabolism Inhibit key enzymes in cancer cell specific metabolic pathways to disrupt tumor cell proliferation & survival Metabolic Immuno-on
Slide 20: Expanding the Playing Field in Rare Genetic Diseases
Expanding the Playing Field in Rare Genetic Diseases (RGD) ~500 Rare Diseases of Metabolism ~5% of Rare Diseases have approved drugs High Medical Need Sources: http://rarediseaseday.us/; https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders; http://150.214.214.5/meta
Slide 21: Rare Genetic Disease Pathogenesis
Rare Genetic Disease Pathogenesis Disrupted metabolic networks DNA Mutated metabolic enzyme Tissue, organ, system Gene therapies Diverse pathophysiology and disease phenotypes Genetic mutation(s) Biochemical defects Toxic or deficient metabolites
Slide 22: The Current Therapeutic Landscape
The Current Therapeutic Landscape Disrupted metabolic networks DNA Mutated metabolic enzyme Tissue, organ, system Gene therapies Emerging, but with delivery hurdles Diet, scavenging, chelation, etc. Palliative care Incompletely addressing disease mechanism, limited beneficial effects Enzyme replacem
Slide 23: Creating a New Wave of Transformational Therapies
Creating a New Wave of Transformational Therapies Understanding and correcting the root cause of the disease Success mostly limited in lysosomal storage disorders Disease-modifying small molecules targeting intracellular pathways leading to transformative outcomes for patients Agios Approach Diverse
Slide 24: Agios RGD Disease Selection Attributes
Agios RGD Disease Selection Attributes Disease Selection Criteria and Differentiated Therapeutic Strategies High Unmet Need Feasible Clinical Path Effective Intervention Strategy
Slide 25: Defining Novel Therapeutic Strategies: Agios' Competitive Advantage
Defining Novel Therapeutic Strategies: Agios’ Competitive Advantage Develop deep insight into mechanism of disease pathophysiology Validate therapeutic strategies in disease models Patient derived cell models and genetically engineered animal models Design small molecule drugs using a combination of
Slide 26: Small Molecule Strategies to Correct Disease Pathology
Small Molecule Strategies to Correct Disease Pathology Metabolite A Metabolite B Metabolite C Enzyme 1 Enzyme 2
Slide 27: Small Molecule Strategies to Correct Disease Pathology
Small Molecule Strategies to Correct Disease Pathology Metabolite A Metabolite B Metabolite C Substrate Reduction: Reduce toxic metabolite B by inhibiting upstream enzyme “Repair” Mutant Enzyme: Activate or stabilize defective protein Enzyme 1 Enzyme 2 ”Bypass” mutant enzyme Activate alternative pat
Slide 28: Phenylketonuria (PKU): Mutations in Phenylalanine Hydroxylase
Phenylketonuria (PKU): Mutations in Phenylalanine Hydroxylase (PAH) PAH fails to process the Phe to Tyr Normal Protein Diet A mixed diet provides your body with Defective PAH enzyme 1. This leads to high levels in the blood which results in neurocognitive defects Increase in Phenylalanine 2. 3. Phe
Slide 29: Phenylketonuria (PKU): Mutations in Phenylalanine Hydroxylase
Phenylketonuria (PKU): Mutations in Phenylalanine Hydroxylase (PAH) PAH fails to process the Phe to Tyr Normal Protein Diet A mixed diet provides your body with Defective PAH enzyme 1. This leads to high levels in the blood which results in neurocognitive defects Increase in Phenylalanine 2. 3. Phe
Slide 30: Therapeutic Strategy: Stabilize Mutant PAH to Rescue Enzyme Activity
Therapeutic Strategy: Stabilize Mutant PAH to Rescue Enzyme Activity Stabilization leads to increase in active protein levels, leading to lower Phe levels different mutations found in PAH Majority result in misfolded protein leading to degradation Agios approach is to stabilize mutant PAH > 900 Sour
Slide 31: Lead Molecule Decreases Blood Phenylalanine in Severe PKU Mouse Model
Agios Lead Molecule Dramatically Decreases Blood Phenylalanine Levels in Severe PKU Mouse Model Blood Phe Concentration Blood Phe concentrations of treated mice normalized 360 Blood Phenylalanine (uM) 120 Severity of disease correlates with extent of phenylalanine elevation Normal Blood Phenylalanin
Slide 32: Lead Molecule Increases PAH Protein Levels in Liver of PKU Mouse
Agios Lead Molecule Increases PAH Protein Levels in the Liver of Severe PKU Mouse Stabilization of mutant PAH protein in knock-in mouse model of severe PKU Blood Phe concentration PAH GAPDH Western blot, 6 hours after final dose Control Compound A WT Blood Phe concentrations of treated mice normaliz
Slide 33: Emerging Portfolio of First-in-Class RGD Programs
Emerging Portfolio of First-in-Class RGD Programs Metabolic Target Program Target Discovery Target Validation Drug Discovery Development Candidate Pyruvate Kinase Activator Follow-Ons Phenylketonuria Erythroid Porphyria Friedreich’s Ataxia Exploratory (Multiple Diseases) Non-Metabolic Target Metabol
Slide 34: Metabolic Immuno-oncology
Metabolic Immuno-oncology Alter immune or cancer cell metabolism to enhance the body’s anti-tumor response Agios Areas of Research Focus Rare Genetic Diseases Restore defective metabolic pathways in disease cells that cause rare genetic diseases of metabolism Cancer Metabolism Inhibit key enzymes in
Slide 35: Agios Metabolic IO Strategy
Agios Metabolic IO Strategy Immunosuppressive Tumor Microenvironment Metabolic Immuno-Oncology (IO) Discover targets with potential for single agent activity Increase response rates by utilizing patient selection strategies Identify mechanism based combination therapies Myeloid-derived suppressor ce
Slide 36: Integrated Metabolomics and Gene Expression Profiling
Integrated Metabolomics and Gene Expression Profiling Source: Agios collaboration with the Artyomov Lab, Washington University St. Louis / Immunity Journal March 2015, Volume 42 Issue 3
Slide 37: Inflammatory and Immunosuppressive Macrophages Have Different Metabolic Programs
Inflammatory and Immunosuppressive Macrophages Have Dramatically Different Metabolic Programs Immunosuppressive Macrophage Inflammatory Macrophage Source: Immunity Journal March 2015, Volume 42 Issue 3 Glucose6P DHAP Pyruvate Citrate AKG Succinate Fumarate Malate Working TCA Cycle UDP-GlcNAc Glutami
Slide 38: Building a Translational Platform to Interrogate the Tumor Microenvironment
Building a Comprehensive Translational Platform to Deeply Interrogate the Tumor Microenvironment Understanding the tumor microenvironment in mouse models and human tumors to: Uncover novel therapeutic mechanisms Discover new strategies for patient stratification Whole Tissue Imaging Single Cell Anal
Slide 39: Building a Translational Platform to Interrogate the Tumor Microenvironment
Building a Comprehensive Translational Platform to Deeply Interrogate the Tumor Microenvironment Treated Tumor Interstitial Fluid Single Cell Analysis Whole Tissue Imaging Vehicle v Glutamine v Lactic acid Plasma TIF Tumor Plasma TIF Tumor Pink = T-Cell metabolite Yellow = B-Cell metabolite Blue = M
Slide 40: Building a Network of Collaborators on Novel Targets and Technologies
Building a Network of Collaborators on Novel Targets and Technologies Ongoing collaborations with 16 leading investigators in immunology and metabolism In vivo immune cell metabolism & T cell exhaustion Identification of cancer-cell intrinsic immunotherapy targets Metabolomic analysis of MCA tumor m
Slide 41: Metabolic Strategies to Activate Immune Cell Killing of Tumor Cells
A Growing Portfolio of Metabolic Strategies to Activate Immune Cell Killing of Tumor Cells Immunosuppressive tumor microenvironment Immunosuppressive Tumor Microenvironment Activation of Tumor Cell Killing by the Immune System Helper T cell Inflammatory dendritic cell Tumor Inflammatory macrophage E
Slide 42: Macrophage Target Inhibitor Shows Immunomodulation and Antitumor Efficacy
Inhibitor of Agios Macrophage Target Shows Predicted Immunomodulation and Antitumor Efficacy Single cell analyses Treated Day 5 T cells Dendritic cells Myeloid derived suppressor cells Tumor Vehicle Day 5 Tumor T cells Myeloid derived suppressor cells Dendritic cells Single cell RNA sequencing of tu
Slide 43: Developing Metabolic Immuno-Oncology Pipeline
Developing Metabolic Immuno-Oncology Pipeline Program Target Discovery Target Validation Drug Discovery Drug Candidate T-cell and Tumor Target Macrophage Target Macrophage Target Tumor Target Metabolic Immuno-Oncology Other Targets (T-cell, Macrophage, Tumor) Metabolic Target Celgene Collaboration
Slide 44: Oncology Research Portfolio
Oncology Research Portfolio Kevin Marks, Ph.D., Senior Director, Head of Cancer Biology
Slide 45: Multiple Paths to Precision Medicines in Oncology
Multiple Paths to Precision Medicines in Oncology Clearly Defined Patient Populations Genetic Target Genetic Context Lineage Target genetically altered Gain-of-function mutations Fusions Amplification Synthetic lethal with an oncogene or tumor suppressor Synthetic lethal with a passenger gene deleti
Slide 46: Directly Drugging Gain-of-Function Mutants Has Yielded Transformative Medicines
Directly drugging gain-of-function (GOF) mutants has yielded transformative medicines But, despite deep sequencing of many tumor types, IDH1/2 remain the only metabolic GOF mutations IDH1/2m Precision Medicine in Cancer Metabolism EGFR WT NSCLC Patients EGFR Mutant NSCLC Patients Source: Zhang, et a
Slide 47: MTAP Deletion Frequency
MTAP Deletion Frequency While Gain-of-Function Driver Mutations Are Scarce, Loss-of-Function Mutations Are Common Sources: Marjon et al Cell Reports. 2016 Apr 19;15(3):574-587; Agios data on file; Illei et al Clinical Cancer Research. 2003 Jun; 9(6):2108-13; MTAP deletion frequencies are from Agios
Slide 48: Deletion of MTAP Makes Cancers Vulnerable to Targeting of MAT2A
A Key Insight: Deletion of MTAP Makes Cancers Vulnerable to Targeting of MAT2A MTAP deletion 1. MTAP enzyme MTA MTR-1P MTAP Chromosome 9p21 deleted in 15% of cancer MTA accumulates MTR-1P MTAP MTAP enzyme is lost 2. Substrate MTA accumulates MTA inhibits PRMT5 PRMT5 SAM Methylation MAT2A 3. Partial
Slide 49: Discovery of First in Class MAT2A Inhibitors
MTAP wt MTAP null Growth Inhibition in Cancer Cells +/- MTAP In vitro biochemical assay Cycloleucine AGI-24512 Cycloleucine Identification of MAT2A Inhibitors MTAP-selective Growth Inhibition % inhibition of MAT2A activity Source: Agios data on file Discovery of First in Class MAT2A Inhibitors and V
Slide 50: Discovery of First in Class MAT2A Inhibitors
MTAP wt MTAP null Growth Inhibition in Cancer Cells +/- MTAP In vitro biochemical assay Cycloleucine AGI-24512 Cycloleucine Identification of MAT2A Inhibitors MTAP-selective Growth Inhibition MTAP-deleted Tumor Xenograft Model MTAP-WT Tumor Xenograft Model MAT2Ai MAT2Ai Tumor volume (mm3) Tumor volu
Slide 51: Preclinical Studies Indicate Potential Across MTAP-Deleted Indications
Preclinical Studies Indicate Potential for Use in Variety of MTAP-Deleted Indications Patient-derived Xenograft (PDX) ‘clinical trial’ Efficacy (%Tumor Growth Inhibition) Patient-Derived Xenograft Models Esophageal (SCC) Model NSCLC (SCC) Model Regressions observed upon single agent AG-270 treatment
Slide 52: Mechanistic Understanding of Pathway Downstream of MAT2A
Emerging Mechanistic Understanding of the Pathway Downstream of MAT2A Source: Data presented at 2018 AACR Conference Gene Expression DNA Replication Genome Integrity RNA splicing concurrent with transcription 1. RNA Pol Splicing Complex Me Me Me Me Splicing complex requires PRMT5 2. PRMT5 SAM Gene E
Slide 53: AG-270 Program Poised for Biomarker-driven Clinical Development
AG-270 Program Is Well Poised for Biomarker-driven Clinical Development Patient Selection Biomarkers Directly assess MTAP-status by IHC MTAP deficient PDAC MTAP positive PDAC 1. Next-gen sequencing for CDKN2A loss 2. Multiple Pharmacodynamic Biomarkers MAT2A inhibition Tumor-selective inhibition of
Slide 54: AG-270 First-in-Human Phase 1 Clinical Trial
AG-270 First-in-Human Phase 1 Clinical Trial Further evaluation of safety, tolerability and clinical activity Randomized Phase 1/2 trials Reduction in circulating concentrations of S-adenosylmethionine (SAM) and elevation of methionine Adequate safety & pharmacokinetics Maximum tolerated dose (MTD)
Slide 55: Systematically Searching for Other MAT2A/MTAP-like Programs
Source: Adapted from Beroukhim et al Nature 2010 Datamining of human tumor data CRISPR/shRNA screening platform Custom bioinformatics to identify best target/genotype pairs Prevalent deletions with significant unmet need Systematically Searching for Other MAT2A/MTAP-like Programs Agios’ oncology res
Slide 56: Novel Selective Vulnerability Target for PTEN-mutant Cancers
Internally identified target with robust target validation in vitro and in vivo Next Wave Target Example: Novel Selective Vulnerability Target for PTEN-mutant Cancers PTEN-selective functional genomics (shRNA) screen Successful validation of Target X – dox + dox – dox + dox PTEN wt PTEN -/- days day
Slide 57: Multiple Paths to Precision Medicines in Oncology
Multiple Paths to Precision Medicines in Oncology Clearly Defined Patient Populations Genetic target Genetic context Lineage Target genetically altered gain-of-function mutations fusions Amplification Synthetic lethal with an oncogene or tumor suppressor Synthetic lethal with a passenger gene deleti
Slide 58: Cell Line Screen Reveals Selective AG-636 Sensitivity in Heme Malignancies
Cell line panel screen reveals selective AG-636 sensitivity in heme malignancies A Chemical Biology Screen Revealed an Unexpected Lineage Dependence on DHODH We tested a library of inhibitors of metabolic enzymes vs 100s of cancer cell lines, searching for selective agents DHODH inhibitor AG-636 blo
Slide 59: DHODH Inhibitor AG-636 is Efficacious in AML
DHODH Inhibitor AG-636 is Efficacious in AML lysozyme locus KI 11/12 screen hits Inhibited DHODH Inhibition of DHODH overcomes differentiation blockade in AML… Source: Sykes et al, Cell 2016 …and drives substantial efficacy in vivo Efficacy in MOLM13 AML model AML PDX model Tumor volume (mm3) Tumor
Slide 60: DHODH Inhibitor AG-636 is Efficacious in DLBCL
DHODH Inhibitor AG-636 is Efficacious in DLBCL Aggressive, triple-hit DLBCL PDX model Efficacy in OCILY19 DLBCL model Vehicle 100 mg/kg BID AG-636 Tumor volume (mm3) Tumor volume (mm3) AG-636 is active in wide range of DLBCL cell lines, including subtypes with poor prognosis [DHODHi] required for 50
Slide 61: Agios Preclinical Oncology Pipeline
Agios Preclinical Oncology Pipeline Program Target Discovery Target Validation Drug Discovery Drug Candidate Oncology Non-Metabolic Target Metabolic Target Metabolic and Non-Metabolic Targets Celgene Collaboration MAT2A Follow-Ons Heme Lineage: AG-636 DHODH Genetically Defined Heme Target Geneticall
Slide 62: Agios Preclinical Pipeline
Agios Preclinical Pipeline Program Target Discovery Target Validation Drug Discovery Drug Candidate Oncology Rare Genetic Diseases Metabolic Immuno-Oncology (Celgene Collaboration) Non-Metabolic Target Metabolic Target Metabolic and Non-Metabolic Targets Celgene Collaboration MAT2A Follow-Ons Heme L
Slide 63: = agios
2 = agios
Slide 64: Ivosidenib Clinical Strategy in Acute Myeloid Leukemia
Ivosidenib Clinical Strategy in Acute Myeloid Leukemia Darrin Miles, Vice President, IDH Program Management
Slide 65: IDH Mutations Across Many Tumor Types
IDH Mutations Across Many Tumor Types ACUTE MYELOID LEUKEMIA (AML) ~20% of Patients Have IDH1 OR IDH2 Mutation ~10,000 IDHm Patients CHOLANGIO- CARCINOMA LOW GRADE GLIOMA ~14 % have IDH1 Mutation ~3,000 IDH1m Patients ~80% have IDH1 Mutation ~9,000 IDH1m Patients Patient numbers represent annual U.S
Slide 66: Multiple Opportunities Across IDHm Hematologic and Solid Cancers
Multiple Opportunities Across IDHm Hematologic and Solid Cancers Originating from Agios Research Platform ACUTE MYELOID LEUKEMIA IDH1m Frontline Non-IC Ivosidenib + Aza Phase 3 (AGILE) Ongoing IDH2m R/R IDHIFA® Approved IDHm Frontline IC-Eligible Ivo/Ena + 7+3 Phase 3 Q4 2018 Start IDHm Frontline No
Slide 67: AML Landscape on the Brink of a Therapeutic Tidal Shift
AML Landscape on the Brink of a Therapeutic Tidal Shift ~50K DIAGNOSED ANNUALLY in U.S. & EU 68 MEDIAN AGE OF DIAGNOSIS 20-25% FIVE-YEAR SURVIVAL RATE ~$2B POTENTIAL AS CORNERSTONE OF FUTURE AML THERAPY 4 NEW MEDICINES APPROVED FOR AML IN 2017 ~20% OF PATIENTS HAVE IDH1 OR IDH2 MUTATION (~10K PATIEN
Slide 68: Shifting the Treatment Paradigm for AML with Precision Medicine
Shifting the Treatment Paradigm for AML with Precision Medicine Sources:1) SEER. Cancer Stat Facts: AML 2015. 2) American Cancer Society. AML 2017. 3) Kumar C. Genetic Abnormalities and Challenges in the Treatment of Acute Myeloid Leukemia. Genes Cancer. 2011; 2:95–107 AML O/S: Klepin, et al, JCO, 3
Slide 69: Clinical Development of IDHm Inhibitors Spans All Treatment Lines
Clinical Development of IDHm Inhibitors Spans All Treatment Lines to Become Cornerstone of Treatment ONGOING BROAD IST STRATEGY HOVON 7+3 PHASE 3 PLANNED BROAD IST STRATEGY NON-IC TREATMENT RELAPSED / REFRACTORY TREATMENT INTENSIVE CHEMO (IC) ~60-70% of AML Patients NON-IC TREATMENT ~30-40% of AML P
Slide 70: Ivosidenib Phase 1 R/R AML Data
Ivosidenib Phase 1 R/R AML Data Median OS 8.8 months overall mOS for CR+CRh has not been reached 9.3 months for non-CR+CRh responders 3.9 months for non-responders Median follow-up, 14.8 months Data cutoff: 12May2017. CR, complete remission; CRh, CR with partial hematologic recovery; RBC, red blood
Slide 71: Ivosidenib Phase 1 Response in Untreated AML and MDS
Ivosidenib Phase 1 – Response in Untreated AML and MDS Source: Data from ASH 2017 aUntreated AML patients not eligible for standard of care therapies in expansion Arm 2 and from dose escalation whose starting dose was 500 mg QD bMDS patients in expansion Arm 3 and from dose escalation whose starting
Slide 72: Molecular MRD-Negative CR Associated with Improved Overall Survival
Molecular MRD-Negative CR Associated with Prolonged Duration of CR+CRh and Improved Overall Survival (R/R AML, BMMCs) MC = Mutation Clearance, defined as the inability to detect the mIDH1 variant allele (lower limit of detection for mIDH1 alleles of 0.02–0.04% (2–4×10-4) from ≥1 on-study time point
Slide 73: IDHm Inhibitors in AML Frontline Setting: Phase 1 Combination Data
Potential for IDHm inhibitors in AML Frontline Setting: Encouraging Data from Ongoing Phase 1 Combination Trials Median age 60.5 years 69% (n=22) de novo AML Combination safe & well tolerated CR+ CRi/CRp rate for all patients = 77% (23 of 30) CR+CRi/CRp rate for de novo patients = 91% (19 of 21) Med
Slide 74: Opportunity to Utilize Event-Free Survival as Primary Endpoint
“Improvement in EFS itself represents benefit to patients” FDA ASH 2017 Opportunity to Utilize Event-Free Survival (EFS) as Primary Endpoint Recent FDA/EMA approval of treatment for newly diagnosed de novo AML based on EFS primary Like OS, an EFS endpoint will reflect direct clinical benefit of ivos
Slide 75: HOVON Phase 3 Intergroup Frontline AML Trial with Celgene
HO150 Phase 3 Intergroup Frontline AML Trial in Collaboration with Celgene Planned for Q4 2018 Newly Diagnosed Patients with AML IDH1m (N=~500) Ivosidenib + 7+3 Regimen IDH2m (N=~500) Placebo + 7+3 Regimen Ivosidenib + Chemo HCT Ivosidenib Placebo Enasidenib + 7+3 Regimen Placebo + 7+3 Regimen Enasi
Slide 76: Phase 3 Frontline AGILE Trial
Randomization 1:1 Double Blinded Ivosidenib 500mg (n=196) + VIDAZA® Primary Endpoint OS Interim analyses for futility and superiority Phase 3 Frontline AGILE Ongoing Placebo (n=196) + VIDAZA® Final OS Analyses Secondary Endpoints: CR, CR+CRh, EFS, ORR Global Phase 3 Frontline IC-Ineligible IDH1m AML
Slide 77: Executing a Broad IST Strategy
Trial Design Line Ongoing Venetoclax combination R/R AML; potential frontline* Beat AML master trial (+ VIDAZA®)** Frontline AML Planned Maintenance** Frontline AML post stem cell transplant VYXEOSTM combination R/R AML VYXEOSTM combination Secondary AML Gilteritinib combination** R/R AML; potential
Slide 78: Accepted ASCO Abstracts
Updated data from expansion phase of the Phase 1 study of ivosidenib in IDH1m R/R AML accepted to ASCO Accepted ASCO Abstracts Updated data from the Phase 1/2 combo trial of enasidenib or ivosidenib with VIDAZA® in newly diagnosed AML accepted to ASCO First clinical data from the Phase 1 study of AG
Slide 79: Ivosidenib Commercial Strategy in Acute Myeloid Leukemia
Ivosidenib Commercial Strategy in Acute Myeloid Leukemia Steve Hoerter, Chief Commercial Officer
Slide 80: Building the Agios IDH Commercial Franchise
Building the Agios IDH Commercial Franchise IDHIFA® commercial performance update Scoping the IDH1 AML opportunity Ivosidenib launch preparations
Slide 81: IDHIFA Launch Performance
IDHIFA® Launch Performance Q3 2017 Q4 2017 Q1 2018 Revenues reported by Celgene; 2017 Payer Mix, Agios Estimates
Slide 82: IDHIFA Launch Performance
IDHIFA® Launch Performance Q3 2017 Q4 2017 Q1 2018 Revenues reported by Celgene; 2017 Payer Mix, Agios Estimates 2% Medicaid
Slide 83: IDHIFA Launch Metrics Update
2017 sales $20M (Q4 sales $13M) Early IDHIFA® Success Sales IDHIFA® Launch Metrics Update 2018 Q1 sales $14M IDH2m testing at ~50% as of October Diagnostic Testing IDH2m testing at ~70% as of January Early IDHIFA® Success IDHIFA® Launch Metrics Update Prescriber Base >250 unique prescribers >300 uni
Slide 84: NCCN Treatment Guidelines Address IDHm+ AML
NCCN Treatment Guidelines Address IDHm+ AML Enasidenib is recommended in patients with relapsed/refractory AML and an IDH2 mutation Enasidenib added as an option in the first-line setting in patients who are not candidates for intensive remission induction therapy, or who decline intensive therapy F
Slide 85: Building the Agios IDH Commercial Franchise
Building the Agios IDH Commercial Franchise IDHIFA® commercial performance update Scoping the IDH1 AML opportunity Ivosidenib launch preparations
Slide 86: AML Landscape on the Brink of a Therapeutic Tidal Shift
AML Landscape on the Brink of a Therapeutic Tidal Shift ~50K DIAGNOSED ANNUALLY in U.S. & EU 68 MEDIAN AGE OF DIAGNOSIS 20-25% FIVE-YEAR SURVIVAL RATE ~$2B POTENTIAL AS CORNERSTONE OF FUTURE AML THERAPY 4 NEW MEDICINES APPROVED FOR AML IN 2017 ~20% OF PATIENTS HAVE IDH1 OR IDH2 MUTATION (~10K PATIEN
Slide 87: New Medicines to Treat AML: Great News for Patients
Fit for Intensive Chemotherapy Not Fit for Intensive Chemotherapy Pre-2017 Today & The Future Treatments based on patients eligibility (or not) for intensive chemotherapy Targeted treatments offering personalized approach Unselected treatments that offer improvements over current SoC New Medicines t
Slide 88: How We Taught Ourselves to Pronounce Ivosidenib
How We Taught Ourselves to Pronounce Ivosidenib
Slide 89: How We Taught Ourselves to Pronounce Ivosidenib
How We Taught Ourselves to Pronounce Ivosidenib
Slide 90: U.S. AML Epidemiology and Treatment Approach – IDH1 Opportunity
U.S. AML Epidemiology and Treatment Approach – IDH1 Opportunity Relapsed/Refractory ~50% Initial targeted indication: ~700 to ~1,100 eligible IDH1m patients per year Currently Untreated U.S. Annual Newly Diagnosed AML Patients ~21K (IDH1m is 6-10%: ~1,300-2,100 patients) Intensive Therapy ~60-70% No
Slide 91: Building the Agios IDH Commercial Franchise
Building the Agios IDH Commercial Franchise IDHIFA® commercial performance update Scoping the IDH1 AML opportunity Ivosidenib launch preparations
Slide 92: Strategic Imperatives for the TIBSOVO Launch
Strategic Imperatives for the TIBSOVO® Launch Physicians test for IDH1m TIBSOVO® is recognized as the best option for IDH1m+ R/R AML Patients have access to TIBSOVO®
Slide 93: Sales Team Deployed to Cover Prescriber Base
Sales Team Deployed to Cover Prescriber Base Top Tier AML Centers
Slide 94: Patient Access
Patient Access Our Approach to Patient Access is Multifaceted Patient Services Copay card for commercial patients Patient Assistance Program Commercial insurance coverage interruption Referrals to independent third-parties for additional support Distribution Channel Limited specialty pharmacy networ
Slide 95: Welcome to myAgios Patient Support Services
Welcome to myAgios™ Patient Support Services Home Financial assistance Distribution network Enroll now Resources Important Safety Information | Prescribing Information | Tibsovopro.com I AM A PATIENT OR CAREGIVER I AM A HEALTHCARE PROVIDER Financial assistance programs Network of specialty pharmacy
Slide 96: We are Launch Ready, Thanks to a Great Team
We are Launch Ready, Thanks to a Great Team
Slide 97: IDH1m Inhibition in Solid Tumors
IDH1m Inhibition in Solid Tumors Susan Pandya, M.D., Senior Medical Director
Slide 98: IDH1 Mutation Present in Multiple Solid Tumors
IDH1 Mutation Present in Multiple Solid Tumors Patient numbers represent annual U.S. and EU incidence CHOLANGIOCARCINOMA ~14% have IDH1 mutation ~3,000 IDH1m patients LOW GRADE GLIOMA ~80% have IDH1 mutation ~9,000 IDH1m patients IDH1m R/R Ivosidenib Phase 3 (ClarIDHY) Ongoing IDH1m Ivosidenib & AG-
Slide 99: The Story of IDHm Inhibition in Solid Tumors is Evolving
The Story of IDHm Inhibition in Solid Tumors is Evolving 2012 Nature. ; 483(7390): 474–478. doi:10.1038/nature10860 Reprinted by permission from Macmillan Publishers Ltd: NATURE 513:110-114, copyright 14 2014, Saha et al.
Slide 100: The Story of IDHm Inhibition in Solid Tumors is Evolving
The Story of IDHm Inhibition in Solid Tumors is Evolving 2012 2013 - 2014 Nature. ; 483(7390): 474–478. doi:10.1038/nature10860 Reprinted by permission from Macmillan Publishers Ltd: NATURE 513:110-114, copyright 14 2014, Saha et al.
Slide 101: The Story of IDHm Inhibition in Solid Tumors is Evolving
The Story of IDHm Inhibition in Solid Tumors is Evolving 2012 2013 - 2014 2014 - Present Nature. ; 483(7390): 474–478. doi:10.1038/nature10860 Reprinted by permission from Macmillan Publishers Ltd: NATURE 513:110-114, copyright 14 2014, Saha et al.
Slide 102: Opportunity for an IDH1m Inhibitor in Solid Tumors
Opportunity for an IDH1m Inhibitor in Solid Tumors Frequency of IDH1 mutation in a variety of solid tumors + unmet need in these indications = opportunity to make a difference in the treatment paradigm for these patients Active clinical development plans in cholangiocarcinoma & glioma Understanding
Slide 103: Cholangiocarcinoma
Cholangiocarcinoma Maeve Lowery, M.B., B.Ch., B.A.O., Trinity College Dublin
Slide 104: Cholangiocarcinoma a Devastating Disease with No Approved Targeted Therapies
Increase in laboratory tests: Cholangiocarcinoma a Devastating Disease with No Approved Targeted Therapies Alkalane phosphastase GGT Total (direct) bilirubin AST/ALT CA 19-9 (elevated in ~65% cholangiocarcinoma) Sources: http://www.alltohealth.com; www.uptodate.com; https://gi.jhsps.org Symptoms: Ab
Slide 105: Cholangiocarcinoma a Devastating Disease with No Approved Targeted Therapies
Sources: CDC National Program of Cancer Registries (NPCR); Epiphany Partners Epic Oncology; Decision Resources; Market Research; Borger DR et al. Oncologist 2012;17:72-9.; Kipp BR et al. Hum Pathol 2012;43:1552-8.; Goyal L et al. Oncologist 2015;20:1019-27. Cholangiocarcinoma a Devastating Disease w
Slide 106: Genetic Alterations in Biliary Tract Cancer
Genetic Alterations in Biliary Tract Cancer GB specific ICC specific Biliary duct common ICC and ECC shared ECC specific EGFR, ERBB3, PTEN, ARID2, MLL2, MLL3, TERT promoter mutation APOBEC signature TP53, BRCA1, BRCA2, PIK3CA mutation Poor-prognosis subtype with high immune checkpoint activity PRKAC
Slide 107: Current Treatments are Limited to Chemotherapy-Based Regimens
Current Treatments are Limited to Chemotherapy-Based Regimens Phase 3 ABC-02 Gemcitabine and Cisplatin – standard of care for newly diagnosed metastatic disease OS – 11.7 months Gem/Cis vs. 8 months for Gem alone PFS – 8 months for Gem/Cis vs. 5 months for Gem alone OS PFS Source: Valle J. N Engl J
Slide 108: Outcomes with Second Line Chemotherapy Remain Poor
Outcomes with Second Line Chemotherapy Remain Poor and Highlight Need for Novel Treatments • Median PFS range is 2-3 months and PFS6 is 10-25% • No available historic placebo PFS benchmark OS mOS – approx. 7 mo PFS mPFS – 2-3 mo Sources: T. Walter et al. / European Journal of Cancer 49 (2013) 329-33
Slide 109: Durable Disease Control with Ivosidenib in Heavily Pre-treated Population
Durable Disease Control with Ivosidenib in a Heavily Pre-treated Population Source: Data from ASCO 2017 61% disease control rate (PR + SD) 0 10 20 30 40 50 60 70 80 90 100 Treatment duration (wk) PR SD PD NA First response Ongoing Radiographic progression On-treatment death
Slide 110: Durable Disease Control with Ivosidenib in Phase 1
Durable Disease Control with Ivosidenib in a Phase 1 Heavily Pre-treated Population 38.5% OF PATIENTS PROGRESSION FREE AND ALIVE AT SIX MONTHS ENCOURAGING DATA SHOWN W/ IVOSIDENIB Ivosidenib well-tolerated in heavily pre-treated population (most common drug-related AEs: fatigue, nausea & vomiting) M
Slide 111: Radiographic Changes in a Patient with a PR on Ivosidenib
Radiographic Changes in a Patient with a PR on Ivosidenib Data from ASCO 2017 Computed tomography scans of a 66-year-old woman with intrahepatic CC previously treated with neoadjuvant cisplatin + gemcitabine who then received AG-120 Source: Data from ASCO 2017
Slide 112: Ivosidenib Promotes Morphologic Changes to Cholangiolar Patterns
Ivosidenib Promotes Morphologic Changes to Cholangiolar Patterns Data from CCF 2018 Sources: 1. Liau JY et al. Mod Pathol 2014;27:1163-73, 2. Komuta M et al. Hepatology 2012;55:1876-88. 3. Komuta M et al. Hepatology 2008;47:1544-56, 4. V. Deshpande, unpublished data, 2017. ‘Normal’ cholangiolar patt
Slide 113: Registration-Enabling Phase 3 Cholangiocarcinoma Study
2:1 Double Blind Randomization (n=186) Ivosidenib Arm 500mg Registration-Enabling Phase 3 Cholangiocarcinoma Study Ongoing Placebo Arm Primary Endpoint: PFS Crossover at time of progression Secondary Endpoints: OS, ORR, safety, QoL Global Phase 3 Previously Treated Advanced IDH1m Cholangiocarcinoma
Slide 114: Clinical Development in Glioma
Clinical Development in Glioma Susan Pandya, M.D., Senior Medical Director
Slide 115: Low Grade Glioma: High Unmet Need
Low Grade Glioma (LGG): High Unmet Need Not Adequately Addressed by Chemotherapy or Radiation Sources: Semin Radiat Oncol 25:219-224; NATURE REVIEWS | NEUROLOGY, APRIL 2016 | VOLUME 12, 204-2016 Mean age of diagnosis of 41 ~80% of LGG patients present with seizure as initial symptom and up to 90% of
Slide 116: IDHm Glioma Is a Distinct Disease
IDHm Glioma Is a Distinct Disease Source: N Engl J Med 2015;372:2481-98
Slide 117: Low Grade Glioma: High Unmet Need
Sources: CDC National Program of Cancer Registries (NPCR); SEER. Cancer Stat Facts; Market research; CBTRUS (Central Brain Tumor Registry in the US); Neurosurg Focus. 2015 Jan; 38(1): E6. Low Grade Glioma: High Unmet Need Not Adequately Addressed by Chemotherapy or Radiation ~11K DIAGNOSED ANNUALLY
Slide 118: Current Treatment Paradigm for IDHm Gliomas
Current Treatment Paradigm for IDHm Gliomas IDH-mutant 1p/19q non-codeleted (ATRX mutant, TP53 mutant) WHO grade II WHO grade III WHO grade II WHO grade III WHO grade IV Watch and wait Radiotherapy PCV (or temozolomide plus radiotherapy temozolomide) Watch and wait Radiotherapy temozolomide (or radi
Slide 119: Durable Stable Disease Signal with Ivosidenib Phase 1 Data
4 8 12 16 20 24 28 32 Treatment duration (mos) 0 Durable Stable Disease Signal with Ivosidenib Phase 1 Data Median treatment duration: 16 mos (range 1.4, 27.1) 63% of patients treated for > 1 yr Source: Data presented at SNO 2017 MR SD PD First response Ongoing Progression Ivosidenib well tolerated
Slide 120: Ivosidenib Phase 1 Data – Reduction in Tumor Growth Rate
Oligodendroglioma 1p19q co-del Biopsy 2007 Temozolomide 2007-2008 No Radiation AG-120 Start 10/2015 H1 MRI: 10/2014 Remains on treatment (18 mos @ cutoff) Best RANO response: SD Ivosidenib Phase 1 Data – Reduction in Tumor Growth Rate Historical 1 Screening On-treatment H1 = historical pre-treatment
Slide 121: Ivosidenib Phase 1 Data – Reduction in Tumor Growth Rate
Ivosidenib Phase 1 Data – Reduction in Tumor Growth Rate Historical 1 - Historical 2 - Screening - Pre-treatment changes On-treatment changes Screening - - AG-120_ late cycle - AG-120_ early cycle Source: Data presented at SNO 2017
Slide 122: Ongoing Phase 1 Perioperative Study with Ivosidenib and AG-881
Evaluate evidence of target engagement showing 2-HG suppression in brain tumor tissue IDH1m Low Grade Glioma Patients Eligible for Resection Active Arm: Ivosidenib or AG-881 Control Arm: N=5 N=~45 Ongoing Phase 1 Perioperative Study with Ivosidenib and AG-881 Evaluating Evidence of Target Engagement
Slide 123: Next Steps in Glioma
Next Steps in Glioma Finalize Decision on Pivotal Path by Year End AG-881 Phase 1 Safety + preliminary efficacy accepted at ASCO 2018 Ivosidenib Phase 1 Robust dataset from SNO 2017 + longer follow-up Ivosidenib + AG-881 Data from Perioperative study Regulatory Feedback in 2018 + + +
Slide 124: PKR Activation & PK Deficiency
PKR Activation & PK Deficiency Chris Bowden, M.D., Chief Medical Officer
Slide 125: PK Activation Represents Opportunities Across Hemolytic Anemias
Inadequate production: ATP deficiency Pyruvate Kinase Deficiency PEP Pyruvate mPKR Proof of concept achieved Cellular demand: ATP production meets demand Normal Red Cell Cellular demand: PEP Pyruvate wtPKR PK Activation Represents Opportunities Across Hemolytic Anemias Increased demand: ATP deficien
Slide 126: Opportunity for AG-348 to be First Disease-Modifying Treatment for PK Deficiency
Opportunity for AG-348 to be the First Disease-Modifying Treatment for PK Deficiency ~3-8K IN U.S. & EU MOST PATIENTS ARE NOT REGULARLY TRANSFUSED 0 APPROVED TARGETED THERAPIES 3.4 g/dL MEAN MAXIMUM HEMOGLOBIN INCREASE WITH AG-3481 PATIENTS ARE BORN WITH DISEASE AND LIVE TO ADULTHOOD TRANSFUSIONS PR
Slide 127: PK Deficiency Carries Lifelong Burden
Infants Jaundice, severe anemia, exchange transfusions Toddlers, Children Splenectomy leading to increased infection risk, antibiotic prophylaxis Adults Iron overload leading to liver cirrhosis, cardiac and endocrine issues PK Deficiency Carries Lifelong Burden
Slide 128: Global Patient Finding Efforts
Global Patient Finding Efforts 2015 2016 2017
Slide 129: Boston Children's Natural History Study
Boston Children’s Natural History Study Initiated in 2014, 278 patients enrolled in 30 sites (North America & EU) Understanding symptoms and complications of the disease: Transfusion burden Incidence & timing of splenectomy Prevalence & treatment of iron overload Identifying patients & treatment cen
Slide 130: PK Deficiency: Burden of Disease is Extensive
PK Deficiency: Burden of Disease is Extensive IRON OVERLOAD (47%) CHOLELITHIASIS (45%) CHOLECYSTECTOMY (40%) SPLENECTOMY (59%) THROMBOSIS (Overall, 7%) (Post-splenectomy, 11%) OSTEOPENIA/ BONE FRACTURES (17%) APLASTIC CRISIS (14%) Grace et al. Blood, prepublished online March 16, 2018 Baseline and R
Slide 131: Mutations Cause a Range of Defective PKR Proteins
Over 300 Mutations Cause a Range of Defective PKR Proteins Sources: R van Wijk, Blood 2005; Bianchi P et al. poster, 2017 ASH Annual Meeting Mutations in PKR have been described in PK deficiency, belonging to one of two categories: Missense mutations cause a single amino acid change in the protein –
Slide 132: PEAK Registry Enrolling Patients
PEAK Registry Enrolling Patients * This list is not exhaustive, and may change Natural History Study countries Potential additional countries for registry* Primary objective is to develop greater understanding of the longitudinal clinical implications of pyruvate kinase deficiency, including: Natura
Slide 133: Physician Opinion of Disease Severity is Highly Variable
Hematologists specializing in benign heme diseases are most familiar Physician Opinion of Disease Severity is Highly Variable and a Function of Patient Experience PK deficiency patients are characterized by the overall disease burden Anemia Iron overload, splenectomy, cholelithiasis Reduced stress r
Slide 134: Living with PK Deficiency
Living with PK deficiency Patients Describe a Constellation of Signs and Symptoms That Challenge Their Efforts to “Be Normal” “I know more about my disease than my hematologist.” Anxiety about keeping disease private from employers Strong desire to participate in advocacy efforts & trials Physical b
Slide 135: Agios PRO Tool Integrates Patient Perspective into Disease Burden
Agios PRO Tool Integrates Patient Perspective into Disease Burden Assesses signs & symptoms and the impact on patients reported outcomes Signs & Symptoms Physical limitations Appearance Daily life Social impacts Emotional impacts Fatigue / tiredness Lack of / low energy Exhaustion Weakness Dizziness
Slide 136: AG-348 Clinical Development Plan
AG-348 Clinical Development Plan
Slide 137: Robust Hemoglobin Increases with AG-348 in DRIVE PK
The baseline value is the average of all central assessments within the screening period (42 days prior to Day 1) Maximum Hb increases observed by genotype Source: Data presented at 2017 ASH Annual Meeting AG-348 continues to be well tolerated Measurements of hormone levels in men at doses ≤50 mg BI
Slide 138: AG-348 ACTIVATE Trial for Non-Regularly Transfused Patients
AG-348 ACTIVATE Trial for Non-Regularly Transfused Patients Screening Randomized, Double-Blind, Placebo Controlled N=~80 Extension Placebo patients cross-over to AG-348 Placebo 5 mg 50 mg 20 mg 1:1 Randomization Optimized AG-348 Dose “Optimized” Placebo Primary Efficacy Endpoint: Proportion of patie
Slide 139: AG-348 ACTIVATE-T Trial for Regularly Transfused Patients
AG-348 ACTIVATE-T Trial for Regularly Transfused Patients Retrospective Collection of Transfusion History Primary Endpoint: Reduction in transfusion burden over a 6 month period compared to the patient’s transfusion history Trial Initiation & Screening Individualized Dose Optimization (Part 1) Optim
Slide 140: PK Activation Represents Opportunities Across Hemolytic Anemias
Inadequate production: ATP deficiency Pyruvate Kinase Deficiency PEP Pyruvate mPKR Proof of concept achieved Cellular demand: ATP production meets demand Normal Red Cell Cellular demand: PEP Pyruvate wtPKR PK Activation Represents Opportunities Across Hemolytic Anemias Increased demand: ATP deficien
Slide 141: AG-348 Improves Red Cell Parameters in Beta-thalassemia Mouse Model
Treatment with AG-348 for up to 2 months shows sustained improvement in hematological parameters Sharp reduction in circulating immature red cells suggests amelioration of ineffective erythropoiesis ~50% increase in lifespan of peripheral RBCs Hemoglobin Reticulocytes ATP AG-348 Improves Red Cell Pa
Slide 142: Thalassemia Phase 2 Proof-of-Concept in Non-Transfusion Dependent Adults
Thalassemia Phase 2 Proof-of-Concept in Non-Transfusion Dependent Adults 50 mg BID 100 mg BID Screening AG-348 Core Treatment Period (N= ~20) 4 weeks 8 weeks ≤ 6 weeks 12 weeks Interim Analysis Extension Treatment or Follow-Up Visit Open-label trial in ~20 patients with hemoglobin < 9.0. Primary end
Slide 143: 2,3-DPG Regulates Hemoglobin Oxygenation in Sickle Cell Disease
2,3-DPG Regulates Hemoglobin Oxygenation in Sickle Cell Disease Sickle cells (SS) have higher 2,3-DPG compared to normal (AA) Sources: Journal of clinical sleep medicine JCSM, 3. 313-5; L J Clin Invest. 1970 Apr; 49(4): 806–812 Decreased O2 affinity can contribute to sickling in SCD Same affinity fo
Slide 144: Therapeutic Hypothesis for AG-348: Modulation of 2,3-DPG and ATP
Therapeutic Hypothesis for AG-348: Modulation of 2,3-DPG and ATP Levels Will Reduce HbS Polymerization Activation of WT PKR in healthy volunteer clinical studies shows ~50% reduction in 2,3-DPG C DPG depletion shifts T to R -DPG +DPG Mean blood concentration-time profiles of 2,3-DPG following multip
Slide 145: Defining the Potential for PKR Activation in Hemolytic Anemias
Defining the Potential for PKR Activation in Hemolytic Anemias Pyruvate Kinase Deficiency Pivotal program underway for global registration PEAK registry and Natural History Study will further define disease burden Life Cycle Expansion Phase 2 proof-of-concept in Thalassemia to start 4Q’18 Planning f
Slide 146: Financial Overview & Q1 2018 Financial Results
Financial Overview & Q1 2018 Financial Results Andrew Hirsch, Chief Financial Officer & Head of Corporate Development
Slide 147: Agios Approach to Drug Discovery and Development Drives Shareholder Value
Agios Approach to Drug Discovery and Development Drives Shareholder Value Discovery Research 6 INDs in 8 years 7th planned for Q4 2018 Discover new cancer or rare genetic disease targets or develop new biological insight to known pathway Rapidly validate the biology pre-clinically Develop small mole
Slide 148: Capital Formation and Investment Approach
Capital Formation and Investment Approach Clinical Portfolio Investment Profit from Commercialized Products External Funding $50-60M Annual Research Discovery Investment 6 INDs in 8 years 7th IND planned for Q4 2018 9 programs in late preclinical development IDHIFA NDA Approval <4 years from 1st pat
Slide 149: Shareholder Value Creation Since IPO
87.94 39.85 $83.77 $18.00 57.6M 31.0M $4.8B $0.6B Shareholder Value Creation Since IPO At IPO (July 2013) Today (May 1, 2018) Market Capitalization +700% Share Count +85% ($1.5 billion raised) Share Price +365% XBI Performance +120% $ $
Slide 150: Clinical Development Decisions Driven By Our Vision and Values
Not likely to pursue clinical investment Aggressive investment and development No clinical investment Measured investment and development Clinical Development Decisions Driven By Our Vision and Values Transform the lives of Patients = Unmet Need/Market Opportunity Scientific Leadership = Assessment
Slide 151: First Quarter Financial Results
First Quarter Financial Results Balance Sheet March 31, 2018 December 31, 2017 Variance Cash, Cash Equivalents and Marketable Securities $995M $568M $427M Total Assets $1,040M $614M $426M Statement of Operations Three Months Ended March 31, 2018 Three Months Ended March 31, 2017 Variance Collaborati
Slide 152: = agios
2 = agios