Exhibit 99.1

Agios in 2016

JPMorgan Healthcare Conference

January 11, 2016 David Schenkein, M.D. Chief Executive Officer

 

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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. Such forward-looking statements include those regarding the potential benefits of Agios’ product candidates targeting IDH1/IDH2 or pyruvate kinase-R mutations or other genetic mutations, including AG-221, AG-120, AG-881, AG-348 and AG-519; its plans and timelines for the clinical development of AG-221, AG-120, AG-881, AG-348 and AG-519; its plans regarding future data presentations; its plans regarding its preclinical development activities; and the benefit of its strategic plans and focus. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “potential,” “hope,” “could,” “would” 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 or the various remarks made during this presentation could also be affected by risks and uncertainties relating to a number of other important factors, including: 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 and 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 maintain key collaborations, such as its agreement with Celgene; and general economic and market conditions. These and other risks are described in greater detail under the caption “Risk Factors” included in Agios’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2015, and other filings that Agios may make with the Securities and Exchange Commission in the future.

Any forward-looking statements contained in this presentation or in remarks made during 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, except as required by law.

 

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We Are Driven By a Clear Vision and Values

RARE GENETIC DISORDERS OF METABOLISM CANCER METABOLISM DYSREGULATED METABOLISM

VISION

Agios is passionately committed to the fundamental transformation of patients’ lives through scientific leadership in the field of cancer metabolism and rare genetic disorders of metabolism

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Building a Great Sustainable Biopharmaceutical Company

Building Late-stage Development & Commercial Capabilities

Continuing to Expand Research Platform

5th Agios

Agios IDH Celgene AG-221 AG-348 medicine 2016 Key

Labs Discovery Partnership /AG-120 Proof of entering Priorities

Open Proof of Mechanism clinic; 200th

Concept employee

2009 2009 2010 2014 2014 2015 2016

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Our 2016 Key Priorities: Maturing into a Late-stage Company

Rapid and broad late stage clinical development for IDHm inhibitors

Demonstrate clinical activity of PKR activators in patients

Advance research and initiate preclinical development of next wave research program

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Novel First-in-Class Clinical Portfolio

Early Stage Late Stage

Candidate Indication Primary Commercial Rights

Clinical Development Clinical Development

R/R AML Phase 3

R/R AML Phase 1 Dose Escalation Expansion 5th Cohort

AG-221 Frontline AML (Fit) Phase 1b Combinations

(IDH2m inhibitor) Frontline AML (Unfit) Phase 1/2 Combinations (Q1’16)

MDS/Heme Malig Phase 1 Expansion 2nd Expansion (2016)

Solid Tumors Phase 1 Dose Escalation Agios U.S. Co-promotion and Royalty

Frontline AML Phase 3 (2H’16)

R/R AML Dose Escalation Expansion

AG-120 MDS/Heme Malig Phase 1 Expansion

(IDH1m inhibitor) Frontline AML (Fit) Phase 1b Combinations

Frontline AML (Unfit) Phase 1/2 Combinations (Q1’16) U.S. Rights EX-U.S. Rights

Solid Tumors Phase 1 Dose Escalation Expansion

IHCC Phase 2 (2H’16)

AG-881 R/R AML Phase 1 Dose Escalation

(pan-IDHm inhibitor) Solid Tumors Phase 1 Dose Escalation Joint Worldwide Collaboration

AG-348 PK Deficiency Phase 2 DRIVE PK

(PK (R) Activator)

AG-519 PK Deficiency Phase 1

(PK (R) Activator)

Celgene agios

 

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Today’s Key 2016 Milestone Announcements

IDHm Inhibitors

Complete enrollment in AG-221 and AG-120 expansion arms in 2H Initiate Phase 3 study of AG-120 in frontline AML in 2H

Initiate MDS expansion arm for AG-221

Initiate randomized Phase 2 study of AG-120 in cholangiocarcinoma in 2H

PKR Activators

Present first data from DRIVE PK trial of AG-348 in 1H

Present first data from AG-519 Phase 1 healthy volunteer study in 1H Present new findings from Natural History Study of PK deficiency in 2H

Outline clinical development plans for PKR activators in beta-thalassemia in 2H

Research

Initiate preclinical development activities and publish on a new cancer metabolism program

 

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Cancer Metabolism: IDH

Using a pill once a day to repair a cancer cell

agios

 

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Repairing an IDH Mutant Cancer Cell

DIFFERENTIATION RESTORED BLO

Inhibitor

IDH Epigenetic

“Re-Wiring” Unchecked Cell Proliferation

Isocitrate mIDH 2HG CANCER

Differentiation aKG

HSC Progenitor Progenitor

IDHm Inhibitor

Leukemia Blast Neutrophil

Day 0 Day 15 Day 28

AG-120, EORTC, 2014

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What’s Possible for IDHm Patients

A Roadmap for Speed and Breadth

Goal

Next

Now

All IDHm patients screened and treated with an IDHm inhibitor for the entire course of their disease

Solid tumors Frontline AML Combination trials Maintenance MDS

Other hematologic malignancies

Relapsed/ Refractory AML

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Three IDHm Inhibitors Provide Maximum Opportunity

AG-221

Potent, selective, reversible inhibitor of mutant isocitrate dehydrogenase-2 (IDH2) In Phase 3 clinical development Oral, once daily dosing, 100mg

AG -120

Potent, selective, reversible inhibitor of mutant isocitrate dehydrogenase-1 (IDH1) In Phase 2 clinical development Oral, once daily dosing, 500mg

AG-881

Brain-penetrant, pan-IDH mutant inhibitor (IDH1 & IDH2) In Phase 1 clinical development Oral, once daily dosing

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IDH Mutations Occur in Multiple Cancers

AML

MDS

IHCC

Chondro

Other solid tumors

Glioma

~40K New Patients/Year; Mutation Occurs Early and Easily Detected with Genomic Testing

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AG-221 and AG-120 Represent a New Treatment Paradigm in AML

AG-221 AG-120

Median response duration: 5.6 months Median response duration: 6.9 months

CR PR CRI Ongoing Progression/death crp mcr first response bone marrow transplant treatment suration (months) death or Progression transplant

First-in-Class, Oral, Potent, Selective, Reversible Inhibitors

With ~300 patients treated, AG-221 and AG-120 demonstrate favorable safety profiles Impressive single agent complete and partial responses in relapsed/refractory IDHm AML

Neutrophil and platelet improvements observed in non-CR responders and some patients with stable disease

Data Presented at ASH, 12/5-6/15

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Phase 1 Programs Rapidly Defined Single-Agent Profile for IDHm Inhibitors in R/R AML

Phase 1 expansion cohorts designed to demonstrate compelling clinical benefit with registration quality data

AG-221 Expansion Phase 2

Expansion Phase 1 Ongoing Dose Escalation

Four 25-patient Arms Completed R/R AML Completed (n=125 patients)

AG-120 Expansion Phase 1

Dose Escalation Three 25-patient Arms Ongoing Completed 125-patient Arm Ongoing

Expect to Complete Enrollment in Both 125-patient Expansion Arms in 2H’16

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Targeting Multiple Lines of Treatment in IDHm AML and Other Hematologic Malignancies

Relapsed AML Newly Diagnosed (Untreated) AML MDS / Other Heme Malig.

2nd+ Relapse Intensive Non-Intensive Frontline to R/R

Phase 1 AG-221 Expansion

Phase 1 AG-120 Expansion

Phase 3 IDHENTIFY

AG-221 vs SOC

Phase 1 Induction (7+3) + AG-221 or AG-120

Phase 1? 2 VIDAZA® + AG-221 or AG-120

(1Q’16)

Phase 1 AG-221 MDS Expansion Cohort (2016)

Phase 3

AG-120 in Frontline AML

(2H’16)

Ongoing

Planned

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IDH Mutations Occur in Multiple Cancers Glioma IHCC Chondro Aml mds other solid tumors ~40K New Patients/Year; Mutation Occurs Early and Easily Detected with Genomic Testing 16

 

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Encouraging AG-120 Phase 1 Data in Solid Tumors

Solid Tumors Glioma

Other chondrosarcoma cholangiocarcinoma treatment duration (weeks) pr sd pd unk/na ongoing progression/death

AG-120 well tolerated (no MTD) and showed signs of clinical activity Reductions in tumor volume observed in some glioma patients

Favorable PK properties, inhibition of 2HG in tumor and reduction in proliferation markers

Data Presented at AACR-NCI-EORTC, 11/8/15

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Clinical Development Path in IDH1m Solid Tumors Will

Be Data Driven

AG-120

IDH1m inhibition; low CNS penetration

Dose-Escalation Expansion

(Completed) (Ongoing)

Randomized IHCC Phase 2

(2H’16)

IHCC

Chondro sarcoma

Glioma

Other IDHm Solid Tumors

AG-881

Pan-IDHm inhibition; high CNS penetration

AG-881 Phase 1 Dose-Escalation (Ongoing)

Potential Expansion

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Rare Genetic Metabolic Disorders: PKR

Transforming a metabolic disorder with a small molecule

agios

 

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Pyruvate Kinase-R (PKR) Activation Has Broad Potential in Red Cell Disorders Normal Red Cell PEP wtPKR Pyruvate Cellular demand: ATP production meets demand Pyruvate Kinase Deficiency PEP mPKR Pyruvate Cellular demand: Inadequate production: ATP deficiency Other Hemolytic Anemias PEP wtPKR Pyruvate Cellular demand: Increased demand: ATP deficiency 20

 

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PK Deficiency: What We Know Today

Disease Overview Rare genetic disease often

presenting at birth as neonatal

Description jaundice

~2400 diagnosed in U.S. and EU5*

Caused by mutations in PK-LR

Etiology gene coding for Erythrocyte

Pyruvate Kinase

Clinical Lifelong hemolytic anemia and

Presentation associated morbidities

PKR enzyme activity and

Diagnosis genetic testing

Disease Pathophysiology

Red Blood Cell Blood Smear Normal PK Deficiency

* Based on genetic data and diagnosis rate

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Source: Zanella. Blood Rev. 2007; 21(4):217; Blood and Bone Marrow Pathology; Wintrobe’s Clinical Hematology; Physician Interviews; Market Research.

 

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PKR Activation Represents Therapeutic Approach to

Treating PK Deficiency

2,3-DPG

pyruvate Glucose atp

AG-348 AG-519

Patient A (R510Q/G511R)

Pkr activity (relative to dmso) 2-3 dpg (relative to dmso) atp (relative to dmso) 24 hrs

Wt vs pkd atp levels rbcs treated with ag-348 24hrs wt control pkd patient log [ag-348 (m)]

AG-348 300 mg q12hr

R

-

PK by Optional

Screening RandomizationStratified genotype 3rd Arm

AG-348 50 mg q12hr

AG-348

L) Dosing period

m Placebo g/ 200 15 mg q12hr

ATP m ( n

i tion 60 mg q12hr a 120 mg q24hr hange 100 120 mg q12hr

c entr e c

lu t con 360 mg q12hr s o 700 mg q12hr

b od 0

A lo Mean + SD b

0 5 10 15 20

Time (day)

Phase 1 NHV, ASH 2014

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AG-348 Global Phase 2 DRIVE PK Study

Open and Enrolling

Transfusion-independent PK-deficient adults n=25 in each arm

Screening

Randomization

Stratified by PK-R genotype

AG-348

300 mg q12hr

Optional 3rd

Arm

AG-348

50 mg q12hr

6-month

dosing

PK

period

PD

Primary endpoints

Safety and tolerability

Secondary endpoints

PK of AG-348

PD response: ATP, 2,3-DPG

Indicators of clinical activity: hemoglobin, hematocrit, reticulocyte count, and other hematologic parameters.

First Data Expected 1H’16

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AG-519 Healthy Volunteer Study Open and Enrolling

AG-519

Potent, highly selective and orally bioavailable PKR activator Differentiated chemical structure versus AG-348 No activity against the aromatase enzyme AG-519 has similar activity in vitro, in vivo and ex vivo (patient samples) relative to AG-348

One protocol, two steps, healthy volunteers

Step 1: Integrated SAD/MAD

4 dose-ascending cohorts: 8 subjects per cohort (n=32) Placebo controlled (6A, 2P)

Step 2: Bioavailability and Food Effect Study

First Data Expected 1H’16

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AG-519 Provides Optionality for Clinical Development

AG-348 Healthy Volunteer Studies (Completed)

AG-348 DRIVE PK PK Deficiency (Ongoing)

AG-519 Healthy Volunteer Studies

(Q1’16)

Efficacy Safety PK

PD

Pivotal Trials:

Adults

Adolescents

Children Beta-thalassemia Studies (Planned)

Clinical Data From Both Trials Available in 1H’16 Will Determine Late-stage Development Path

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Research

Initiating the development of a new research program

 

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Novel First-in-Class Research Portfolio

Target Validation Compound Optimization

Target C

Two Cancer Metabolism

Multiple Other Oncology Targets

Wave

Rare Genetic

Multiple RGD Targets

Metabolic Disorders

Cancer Metabolism Multiple

Oncology Three Targets

Wave Rare Genetic Multiple RGD

Metabolic Disorders Targets

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Prevalent Deletions of MTAP Create Sensitivity to a Novel Pathway With Multiple Therapeutic Targets

Deletion of metabolic gene adjacent to tumor suppressor p16/p14

chr9p21 MTAP p16/p14

genetic selection markers ~75,000 new patients/year in U.S. with MTAP deletion across many indications

% mtap homozygous deletion (primary tumors)

Bladder melanoma brain lung pancreas breast esophageal carcinoma head & neck squamous kidney renal papillary colon adenocarcinoma dlbcl all mcl cml- balst crisis

MTAP-deleted Tumors Constitute a Large, Genetically Defined Patient Population

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Prevalent Deletions of MTAP Create Sensitivity to a Novel Pathway With Multiple Therapeutic Targets

Upstream metabolite MTA accumulates when MTAP is deleted

MTA

(MTAP substrate)

Vulnerable pathway

with multiple

Therapeutic targets

Target 1

Target 2

Target 3

Druggable by Agios inhibitors with precision medicine approach

Target MTAP- Inhibitor

deleted Tumor Xenograft Model

MTAP-WT Target

Tumor Inhibitor

Xenograft Model

Agios Has Developed Potent and Orally-bioavailable Inhibitors of an MTAP-selective Target

Fold change in mtap-deleted cells metabolites mtap selectivity score mtap-deleted tumor xenograft model mtap-wt tumor xenograft model vechicle target inhibitor days post implant s.e.m

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Key Takeaways

Focus on Strategic Priorities and Execution:

Continue rapid, broad late-stage clinical development for our

IDHm inhibitors

Demonstrate clinical activity of our wholly owned, PKR activators in patients

Advance research and initiate preclinical development of a new research program

Building a great sustainable biopharmaceutical company

Passionate in our vision to change patients’ lives

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