Agios Pharmaceuticals, Inc. · NASDAQ:AGIO
Agios Pharmaceuticals — Investor Presentation (January 2014)
33 slides from Agios Pharmaceuticals's investor presentation, Jan 13, 2014
Slide 1: January 2014
Exhibit 99.1 The people pictured here are some of the many friends and family of Agios employees affected by cancer. All of us at Agios are passionate about transforming patients lives. This is our vision and what motivates, inspires, and drives us. January 2014 Agios Pharmaceuticals – CONFIDENTIAL
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements This presentation and various remarks we make during this presentation contain forward-looking statements of Agios Pharmaceuticals, Inc. within the meaning of The Private Securities Litigation Reform Act of 1995, including statements regarding Agi
Slide 3: Driven By Clear Corporate Vision and Values
Driven By Clear Corporate Vision and Values VISION Agios is passionately committed to the fundamental transformation of patients’ lives through scientific leadership in the field of cancer metabolism and inborn errors of metabolism
Slide 4: Building a Great Multi-product Company
Building a Great Multi-product Company Disruptive Area of Biology A leader in field of dysregulated cellular metabolism – a Precision Medicine breakthrough area for drug discovery and development Biomarkers for patient selection for every program Agios leadership team is highly accomplished in drug
Slide 5: Agios Leadership
Agios Leadership Management Board of Directors David Schenkein, M.D. David Schenkein, M.D. Chief Executive Officer and Director 20+ yrs experience in hematology and medical oncology Previously, SVP of Clinical Hematology / Oncology at Roche / Genentech and SVP of Clinical Research at Millennium Kevi
Slide 6: Deep Understanding of Metabolic Pathways Drives Development of Transformational Medicines
Deep Understanding of Metabolic Pathways Drives Development of Transformational Medicines High Throughput How many metabolites Mass Spec Analysis Static view exist in a single point at a given moment in Cell time? Culture How quickly are metabolites moving along enzymatic Flux pathways? Biochemistry
Slide 7: Novel First-in-Class Portfolio: Precision Medicine Approach
Novel First-in-Class Portfolio: Precision Medicine Approach Upcoming Est. # of PrimaryCommercial Research Development Milestones Patients Rights Development Programs: AG-221 Ph1 on-going Expansion Multiple (IDH2m inhibitor) Cohorts cancers Late 2014 ~11,000 AG-120 Multiple IND filed FIH studies (IDH
Slide 8: Cancer Metabolism Product
Cancer Metabolism Product New Validated Development Phase 1 Targets Program Candidate Multiple Ascending Dose Study Celgene Program licensed confirms and commits to Split License Co-commercialize License program 1 of 3 Programs 2 of 3 Programs U.S. rights $120mm milestones Celgene option term $120mm
Slide 9: Cancer Metabolism
CANCER METABOLISM AG-221 (IDH2M INHIBITOR) AG-120 (IDH1M INHIBITOR)
Slide 10: Link between Dysregulated Cellular Metabolism and Cancer is a Proven Concept
Link between Dysregulated Cellular Metabolism and Cancer is a Proven Concept 1920s 1970s 2000s HALLMARKS OF CANCER: THE NEXT GENERATION Douglas Hanahan and Robert A. Weinberg Otto Warburg PET Scans Hallmarks of Cancer Normal Warburg tissue Effect Agios Pharmaceuticals – CONFIDENTIAL 10
Slide 11: Metabolome: Untapped Opportunity For Novel Therapeutic Targets
Metabolome: Untapped Opportunity For Novel Therapeutic Targets Metabolome: 50-100 novel targets Mutations in key metabolic enzymes (e.g. IDH) Cancer specific isoforms of metabolic regulating enzymes Dysregulated metabolic pathways within cancer cells Agios Pharmaceuticals – CONFIDENTIAL 11
Slide 12: Emergence of IDHm Targets validates Agios' approach
Emergence of IDHm Targets validates Agios’ approach Two normal metabolic enzymes (IDH1 and IDH2) mutated in a wide range of cancers Agios makes discovery that IDH mutants create the oncometabolite 2HG 2-hydroxyglutarate (2HG) — Gain of function with a new metabolic pathway 2009 Agios Pharmaceuticals
Slide 13: IDH1m and IDH2m: Two Distinct Genetically Defined Patient Populations
IDH1m and IDH2m: Two Distinct Genetically Defined Patient Populations Product Indication % IDHm Est. # pts.*** Low grade glioma & 2ary GBM** 70% 11,000 Chondrosarcoma >50% 4,600 Acute Myeloid Leukemia (AML) 7.5% 3,600 IDH1m MDS/MPN 5% 2,000 Intrahepatic Cholangiocarcinoma 20% 1,600 (~31,000*) Others
Slide 14: 2-Hydroxyglutarate, an Oncometabolite: A Surrogate for Treatment Effect & Clinical Benefit
2-Hydroxyglutarate, an Oncometabolite: A Surrogate for Treatment Effect & Clinical Benefit SPECIFIC MEASURABLE CAN BE IMAGED Brain Tumor Samples Blood Samples MRI / MRS 2HG *Linda Liau / UCLA Agios Pharmaceuticals – CONFIDENTIAL 14
Slide 15: IDH Mutations and 2-hydroxyglutarate
IDH Mutations and 2-hydroxyglutarate DIFFERENTIATION BLOCKED Epigenetic “Re-Wiring” Unchecked Cell Proliferation Isocitrate 2HG CANCER KG HSC Progenitor Progenitor DIFFERENTIATION RESTORED Inhibitor Isocitrate 2HG Normal Cell Death / HOMEOSTASIS KG Differentiation HSC Progenitor Mature Cell Agios Ph
Slide 16: AG-221 Can Reverse Differentiation Block in Primary Patient Samples
AG-221 Can Reverse Differentiation Block in Primary Patient Samples Agios publication in Science (2013) Lower blast count and higher percentage of differentiated cells in AG-221 treated samples Agios Pharmaceuticals – CONFIDENTIAL 16
Slide 17: AG-221 Induces Dose-Dependent Survival Benefit
AG-221 Induces Dose-Dependent Survival Benefit Compelling in vivo single agent survival benefit in aggressive IDH2m AML model AG-221 treated animals also have: — Lower 2HG level and tumor burden — Dose-dependent increase in markers of differentiation Agios Pharmaceuticals – CONFIDENTIAL 17
Slide 18: AG-221 (IDH2m Inhibitor) Summary
AG-221 (IDH2m Inhibitor) Summary AG-221: Potent & selective inhibitor of IDH2 mutations Profile and — Potent (IC50 = 12nM) and reversible IDH2m inhibitor Status — Once or twice daily oral dosing Phase 1 started in Q3-2013, enrollment on track Clinical Plan Hematologic malignancies MTD Multiple Poten
Slide 19: Acute Myelogenous Leukemia
Acute Myelogenous Leukemia Most common acute leukemia affecting adults - ~15,000 patients diagnosed per year in US - Average age of diagnosis 50-70 Dismal long term survival rate - ~10,000 deaths per year in US - Long term survival varies widely by age and risk factors Goal of therapy is to induce r
Slide 20: AG-120 (IDH1m Inhibitor) Summary
AG-120 (IDH1m Inhibitor) Summary AG-120: Potent & selective inhibitor of IDH1 mutations Profile and — Potent (IC50 = 8nM) and reversible IDH1m inhibitor Status — Once or twice daily oral dosing On track for Phase 1 in early 2014 Clinical Plan Hematologic malignancies MTD Multiple Phase 1 dose escala
Slide 21: IDHm in Chondrosarcoma & Cholangiocarcinoma
IDHm in Chondrosarcoma & Cholangiocarcinoma Chondrosarcoma Cholangiocarcinoma Rare malignant cancer of cartilage & Rare cancer of the bile ducts bone Majority of tumors are incurable Majority of tumors are incurable Chemotherapy & radiation are Surgery followed by chemotherapy standard of care are s
Slide 22: Emergence of IDH Target is a Fundamental Component of Agios' Cancer Metabolism Program
Emergence of IDH Target is a Fundamental Component of Agios’ Cancer Metabolism Program Two normal metabolic enzymes (IDH1 and IDH2) mutated in cancers — Gain of function with a new metabolic pathway — Agios discovered that IDH mutants create the oncometabolite 2HG 2HG Agios elucidated the mechanism
Slide 23: Inborn Errors of Metabolism
INBORN ERRORS OF METABOLISM AG-348 (PYRUVATE KINASE DEFICIENCY)
Slide 24: Agios Approach to Inborn Errors of Metabolism
Agios Approach to Inborn Errors of Metabolism ERT –Traditional Agios Approach – Transformative Potential to Correct Therapeutic Approach Metabolic Pathway Defects with Small Molecules Vast majority of IEMs lack Re-activate mutant enzyme therapeutic options: Enzyme 2 Enzyme Replacement (activated) Th
Slide 25: Pyruvate Kinase (PK) Deficiency: Rare Hematological IEM Without Therapy
Pyruvate Kinase (PK) Deficiency: Rare Hematological IEM Without Therapy Autosomal recessive disorder Blood smear in PKD characterized by chronic hemolytic anemia Rare genetic disease - Estimated 1,000-3,000 in USA Poor prognosis - Presents in infancy or childhood with severe hemolytic anemia and jau
Slide 26: Therapeutic Approach to Treating PK Deficiency
Therapeutic Approach to Treating PK Deficiency Glycolysis is the only source of energy (ATP) for red blood cells PKR enzyme catalyzes the final step in glycolysis in red blood cells In PK Deficiency, low PKR activity leads to low ATP levels and high rate of hemolysis in red blood cells Agios has dev
Slide 27: Agios Activators Show Early Efficacy in Ex-Vivo Patient Samples
Agios Activators Show Early Efficacy in Ex-Vivo Patient Samples AG-348 improves kinetic defect of AG-348 corrects ATP deficit in patient mutant enzymes red blood cells (R486W / G341A) Compound heterozygous patients have 3-10% residual activity - Parents each carry one mutation, clinically normal wit
Slide 28: AG-348 Summary
AG-348 Summary AG-348: Potent & selective activator of PK-(R) mutations — Reversible and orally bioavailable Profile and — Once or twice daily oral dosing Status — IND activities substantially completed, clinical trials to initiate in mid-2014 — Natural history study being launched by Agios & invest
Slide 29: Financial Overview
>= agios FINANCIAL OVERVIEW < INB . Et METABOLI CANCER DYSREeae METABOLI METABOL|sj,
Slide 30: Financial Summary ($ in thousands)
Financial Summary ($ in thousands) Financial support has been strong from investors — Raised $385M in 3+ years — Celgene Collaboration has provided $141M of non-dilutive funding — Significant ongoing financial commitment, including R&D funding, payments to extend agreement, milestones and royalties
Slide 31: Potential Timeline & Milestones
Potential Timeline & Milestones 2H 2013 2014 2015 2016 2017 FIH IDH2(1) Proof of Concept Cancer – Multiple Indications Late Development IEM – D-2HG Aciduria (1) FIH IDH1 Proof of Concept Cancer – Multiple Indications Late Development (1) FIH PKR Proof of Concept IEM – Pyruvate Kinase Deficiency Late
Slide 32: Building a Great Biopharmaceutical Company
Building a Great Biopharmaceutical Company Drive to Anticipated Fast Start and Build the Clinic milestones 2009-2012 2013-2014 2014 Labs open in January AG-221 in Phase 1 trial AG-221 initiating 2009 expansion cohorts and Potential for 2 more novel presenting dose escalation Major breakthrough on da
Slide 33: Hire great people, think big, have fun, follow the science and do what's right for patients
“Hire great people, think big, have fun, follow the science and do what’s right for patients” 33
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