Abbvie 2016 R&D Day Presentation

AbbVie R&D Day Chicago, IL | June 3, 2016 Forward-Looking Statements and Non-GAAP Financial Information

Some statements in this presentation may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. This presentation contains GAAP and certain non-GAAP financial measures. Non-GAAP financial measures are adjusted for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in AbbVie’s reconciliation tables. AbbVie’s management believes non-GAAP financial measures provide useful information to investors regarding AbbVie’s results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are provided in AbbVie’s quarterly earnings releases posted on the company’s website at www.abbvieinvestor.com. During the course of this meeting, AbbVie will be presenting information about the uses of AbbVie products and AbbVie compounds in clinical development that have not been approved by the U.S. FDA. AbbVie, in no way, intends to recommend or imply that any AbbVie product or compound in development should be used for unapproved uses, or is safe or effective for uses not approved by the FDA.

Richard Gonzalez AbbVie’s R&D Strategy: Re-Stating Standard of Care

Level of Therapeutic Restatement

Cure or Long-Term, Deep, Durable Early-Stage

Disease Control Pipeline

Statement -

Meaningful Late-Stage

SOC SOC Re Improvement vs. Standard of Care Pipeline

Current Standard of Care

Stage of Pipeline Development

AbbVie Mission

Create an innovation-driven, patient-focused, specialty biopharmaceutical company capable of achieving top-tier performance through outstanding execution and a consistent stream of innovative new medicines

Compelling Patient Differentiated Economic Value Innovative Benefit Clinical Performance Medicines Elevate standard of care and address significant unmet need

Oncology Uniquely positioned with growing leadership position in Hematologic Oncology; Rova-T provides strong foundation for Solid Tumors

Leveraging deep scientific expertise to develop next-generation

Immunology biologics and small molecules that elevate standard of care Core Therapeutic Focus Therapeutic Core Virology Highly competitive next-generation HCV combination that addresses remaining unmet medical need

Developing disease-modifying therapies for Alzheimer's disease,

Focus Neuroscience multiple sclerosis and other neurodegenerative conditions Emerging Emerging

Focused investments in areas that fit our core strengths

Other (i.e., Elagolix, cystic fibrosis collaboration, atrasentan, etc.)

Targeted Targeted Investment

Heightened our level of R&D spend to reflect 1 the meaningful opportunities in our pipeline

Built upon already strong capabilities with the 2 addition of new talent to our R&D organization

Strengthened discovery efforts through collaborations 3 with leading academic and other institutions

Augmented our pipeline through concerted focus on 4 strategic licensing, acquisition and partner activity

De-risked key late-stage programs through numerous 5 positive data readouts

50+ Additional Innovative Early-Stage Near-Term Growth Assets Development Programs Opportunities

• Eight key, late-stage de-risked assets • Robust portfolio of promising • Early-stage development programs • High probability of regulatory programs in areas of high unmet need and commercial success • Have already established strong • Enhanced discovery platforms have • Differentiated profiles proof-of-concept for numerous high potential for continued asset assets generation to drive development • On market today or poised to efforts going forward launch over the next 2-3 years

• Imbruvica • Anticipate key data readouts from • Entering clinic with novel immuno- • Rova-T several programs over next 12-24 oncology and neuroscience assets months to determine next steps • Risankizumab • New discovery platforms, including o Veliparib Calico and Stemcentrx, augment • Venclexta o ABT-414 existing discovery/early development • ABT-494 o Atrasentan efforts, have potential to accelerate • Next-Gen HCV asset generation o Several DVD-Ig programs • Elagolix • Early-stage programs to begin driving o Partnered assets (dual PI3K, IL-6 • Zinbryta growth in mid-2020s and beyond nanobody, etc.)

Asset Details Imbruvica Currently approved for five indications, including recent label update to include 1L CLL; numerous mid- On-market with five approved indications, and late-stage studies underway for range of blood cancers additional indications expected over next several years

Venclexta First-in-class BCL-2 inhibitor recently approved for first indication; mid-to-late-stage development On-market with initial indication, additional ongoing for numerous hematologic malignancies indications expected over next several years

Zinbryta Pivotal data demonstrated significant benefit vs. active comparator; regulatory submissions under 2016 Launch review, decisions expected mid-2016

Next-Gen HCV Mid-stage data indicate combination can deliver cure rates approaching 100% across genotypes; 2017 Launch pivotal data expected 2H16

Rova-T Compelling Phase 1/2 data in relapsed SCLC; Phase 3 underway; potential in a variety of solid tumors 2018 Launch with DLL 3 expression

Elagolix Compelling profile illustrated in two registrational trials; on track for regulatory submission in 2017 2018 Launch

ABT-494 Phase 2 RA trials demonstrated potential for best-in-class profile in TNF-IR and MTX-IR; 2019 Launch comprehensive Phase 3 program now underway

Risankizumab Phase 2 Ps study illustrated potential for best overall profile; Phase 3 currently underway, with 2019 Launch potential to advance in several other immune-mediated conditions

$25-30BN*

>$18BN Imbruvica

Rova-T

Risankizumab

Venclexta

ABT-494

Next-Gen HCV

Elagolix Zinbryta Humira 2020 De-Risked Late-Stage Assets

*Represents nominal peak-year revenue opportunity for eight key near-term growth assets

• Compelling, de-risked late-stage pipeline poised to fuel long-term growth

AbbVie offers top-tier • Early-stage pipeline includes programs with the potential to dramatically re-state standard of care revenue and EPS growth, significant cash • Strong track record of execution flow and strong return of capital to • Attractive return of capital philosophy, balanced between shareholders supporting growth and returning cash to shareholders • Remain committed to delivering on our long-term objectives

• Double-digit EPS growth on average expected through 2020

Michael Severino, M.D. A Number of Important Considerations Guide Our R&D Strategy

Unmet Medical Need

Clinical Novel Translation Biology

Core New Capabilities Technologies

• Grow our strong position in hematologic malignancies Oncology • Establish a foundation in solid tumors • Leverage our experience in immunology to develop next-generation immuno-oncology therapies

• Use core skills in immunology to develop next-generation Immunology therapies that raise the standard in Rheumatology, Dermatology and Gastroenterology

• Capitalize on emerging biology and new technologies Neuroscience to expand into Alzheimer's disease and the neurodegenerative components of multiple sclerosis

• Pursue next-generation regimens that address remaining HCV unmet need

• Bring an important new therapeutic option to women Elagolix with endometriosis and uterine fibroids

Cystic • Explore whether new insights in biology and medicinal Fibrosis chemistry can lead to a transformational therapy

We Are Proud of Our Talent at AbbVie Recent hires or new to role

Tom Hudson, M.D. Brad Shotwell, Ph.D. VP, Oncology Discovery/Early Development Senior Group Leader, Hit to Lead Chemistry Eric Karran, Ph.D. Laura Gasparini, Ph.D. VP, Foundational Neuroscience Center Project Director, Neuroscience Rob Scott, M.D. Albert Lai, Ph.D. CMO and VP, Development Project Director, Oncology Shao-Lee Lin, M.D., Ph.D. Guowei Fang, M.D. VP, Global Therapeutic Areas Head of Discovery, Pharmacyclics and International Development Patrick John Marroum, Ph.D. Laura Gault, M.D., Ph.D. Director, Biopharmaceutics, Clinical Pharmacology Neuroscience, Clinical Development and Pharmacometrics Chris Miller, Ph.D. Phil Hajduk, Ph.D. Director, Genetics & Genomics Research VP, Research Informatics Anthony Slavin, Ph.D. Paul Peloso , M.D. Director, Immunology Biology Group Medical Director, Elagolix, General Medicine TA Susie Jun, M.D., Ph.D. Maureen Kelly, M.D. VP, Oncology Translational Medicine Group Medical Director, Risankizumab, Immunology TA Therese Podrebarac, M.D. Adam Petrich, M.D. VP, Immunology Development Associate Medical Director, Oncology

WEST COAST Oncology Redwood City, CA South San Francisco, CA Sunnyvale, CA

LAKE COUNTY EAST COAST Neuroscience Cambridge, MA Immunology Worcester, MA In addition, AbbVie has an R&D presence around the world

Academic Collaborations Industry Partnerships Acquisitions

Calico

Not a comprehensive list

Portfolio of ~20 programs targeting fundamental biological mechanisms that underlie neurodegeneration, cancer and other diseases Primary of aging causes Integrative of tissue damage damage response

Responses to damage

Adapted from Cell 153, June 6, 2013

R&D Spend ($BN) R&D Spend as % of Sales $4.0 20% $3.5 $3.0 $2.5 $2.0 15% $1.5 $1.0 $0.5 $0.0 10% 2013 2014 2015 2013 2014 2015

Note: Non-GAAP; excluding specified items

Late-Stage NME Success Rates Industry Portrait vs AbbVie 100% 83% (6)

80%

60% Industry Success Rates 44% (2006-2014, error bars (18) represent range of three-year averages) 40% Recent AbbVie Success Rates (2012-present) 20%

0% Phase 2 Phase 3

Source: Pharmaceutical Benchmarking Forum/KMR 2015; industry Portrait defined as combined data from all pharma companies participating in PBF/KMR Benchmarking Forum (xx) Numbers in parenthesis indicate number of phase events (Go/no-go decisions) for ABBV

Phase I Phase II Registrational/Phase III Submitted Recent Approvals

Rova-T: Neuroendocrine Venclexta: AML Rova-T: SCLC Imbruvica: CLL (TN, 65+; EU) Humira: HS (U.S. and EU) Tumors Venclexta: iNHL/DLBCL Venclexta: CLL (Relapsed/Refractory) Venclexta: CLL (R/R, 17P del; EU) Humira: New Formulation SC002: Solid Tumors Venclexta: Multiple Myeloma Venclexta: CLL (Front-line; Unfit) Humira: New Pen Device SC003: Solid Tumors Duvelisib: iNHL (R/R) Imbruvica: Pancreatic Cancer Humira: Uveitis (U.S. and EU) PTK7*: Solid Tumors Duopa: Advanced Parkinson’s Imbruvica: Multiple Myeloma Imbruvica: DLBCL (TN) Zinbryta: Multiple Sclerosis EFNA4*: Solid Tumors Viekira 3QD: HCV (U.S. and EU) Imbruvica: AML Imbruvica: FL (R/R) (U.S. and EU) ABBV-838: Multiple Myeloma Imbruvica: FL (TN) Imbruvica: MCL (TN) Viekira Pak: HCV ABBV-399: Solid Tumors Imbruvica: MZL (R/R) Duvelisib: CLL (R/R) Viekira Pak: RBV-free (GT1b Imbruvica: Graft V Host Elotuzumab: Multiple Myeloma (TN) ABT-165: Solid Tumors cirrhotic) Veliparib: NSCLC (Squamous) ABT-RTA 408: Solid Tumors Technivie: HCV (GT4) Risankizumab: Crohn’s Disease Veliparib: NSCLC (Non-squamous) ABBV-075: Solid Tumors 2-DAA Japan: HCV (GT1b) and Hem Onc Risankizumab: PsA Veliparib: Breast Cancer (Neoadjuvant) ABBV-085: Solid Tumors Risankizumab: Asthma Veliparib: Breast Cancer (BRCA) Imbruvica: CLL (TN, U.S.) ABBV-221: Solid Tumors ABT-122: RA Veliparib: Ovarian Cancer Imbruvica: CLL

Select PipelineAssets Select Imbruvica: Solid Tumors ABT-122: PsA ABT-414: GBM (R/R combo with B/R) ABT-494: Crohn’s Disease Empliciti: Multiple Myeloma ABT-981: Osteoarthritis Risankizumab: Psoriasis (Relapsed/Refractory; U.S. EU) ABT-957: Alzheimer's Oncology ALX-0061: RA ABT-494: RA Venclexta: CLL (R/R 17P del; US) ABBV-8E12: PSP & AD Immunology ABT-555: MS and SCI ABT-RTA 408: FA &MM ABT-493/ABT-530: HCV Neuroscience

HCV/Liver Disease ABBV-974: Cystic Fibrosis Elagolix: Endometriosis Other ABBV-2222: Cystic Fibrosis Elagolix: Uterine Fibroids ABBV-2451: Cystic Fibrosis Atrasentan: Diabetic Nephropathy

• 8 products currently in pivotal development or recently launched • Potential for >20 new drug or new indication approvals by the end of 2020, including seven approvals expected to contribute in 2016 and beyond • Recent data readouts continue to de-risk key assets, increasing our level of confidence in high likelihood of clinical, regulatory and commercial success

Venclexta Imbruvica Rova-T

Elagolix Zinbryta (Endometriosis, Uterine Fibroids)

Next-Generation HCV ABT-494 Risankizumab

2016 2017 2018

(PHOENIX) P3, 1L DLBCL * (DAWN) P2, r/r FL (PCYC-1126e) P3, 1L CLL *  (RESONATE-2) 1L CLL (approval) (ILLUMINATE) P3, 1L CLL/SLL (+G vs CG) * (PCYC-1121) P2, MZL (PCYC-1137) P2/3, Pancreas * (PCYC1127 ) P3, 1L & r/r WM * SHINE) P3, 1L MCL * (PCYC-1138) P2, r/r MM * (SELENE) P3, r/r FL/MZL *  (HELIOS) r/r CLL/SLL (MURANO) P3, r/r CLL (+R) P1, r/r NHL (+BR) (label expansion, +BR) P2, r/r CLL after BRCi P1, r/r MM (CONTRALTO) P2, r/r FL (+R vs BR) P1, AML (+dec, +aza) P1, r/r CLL & SLL (CAVALLI) P2,1L DLBCL (+RCHOP P1, AML (+Ara-C) 17p del CLL (approval)  (+R, +G, +BR) vs RCHOP) P1, r/r CLL & NHL

Oncology  P1, 1L GBM P1, r/r MM (VELA) P3, 1L NSCLC SQ (BRIGHTNESS) P3, neo-adjuvant TNBC (+bortez/dex) (VESTA) P3, 1L NSCLC NSQ (BROCADE3) P3, 1-3L BRCA Breast

(INTELLANCE-2) P2, 2L GBM (INTELLANCE-J) P1/2, GBM

ABT-122 ABTABT-981-981 ABT-981 ABBV-599 ABT-494 Anti-TNF-Steroid ADC Risankizumab Anti-TNF/IL-17 ILIL-1-1αα//ββ IL-1 α/β JAK-BTK Phase 1 JAK Phase 1 IL-23 PsA Phase 2 HandHand OA OA Phase Phase 2 2 Knee OA Phase 2 RA Phase 3 Pso Phase 3

ALX-0061 Risankizumab ABT-494 IL-6 IL-23 JAK AD Phase 2 RA Phase 2 CD Phase 2

ABT-308 ABT-494 ABBV-323 ABBV-553 Risankizumab ABT-494 Risankizumab IL-13 CD40 IL-23 Immunology JAK RORgT Phase 1 JAK IL-23 EoE Phase 2 CD Phase 2 Phase 2 PsA Phase 2 UC Phase 2 UC Phase 2

MS: First patient dosed SCI: First patient dosed MS: Initial evidence of biologic activity SCI: Initial evidence of biologic activity

ALZ: First patient dosed PSP: Additional evidence of biologic activity

ALZ: Initial evidence PSP: First opportunity to PSP: Initial evidence of biologic activity demonstrate clinical efficacy

of biologic activity Neuroscience

Commercialization of HCV Next Generation HCV

ENDO: Solstice ENDO: Solstice ENDO: Final ENDO: Regulatory ENDO: Regulatory

6mo data 12mo data data submission approval Elagolix

UF: Phase 3 #1 UF: Phase 3 #2 UF: 12mo 6mo data 6mo data data

Oncology Overview Michael Severino, M.D. Stemcentrx Brian Slingerland Scott Dylla, Ph.D. Oncology Imbruvica Danelle James, M.D., M.S. Venclexta, Veliparib and ABT-414 Gary Gordon, M.D., Ph.D. Discovery and Early Development Thomas Hudson, M.D.

ABT-494 and Risankizumab Shao-Lee Lin, M.D., Ph.D. Immunology Highlights from Immunology Discovery Lisa Olson, Ph.D.

HCV HCV Shao-Lee Lin, M.D., Ph.D.

Elagolix Elagolix Shao-Lee Lin, M.D., Ph.D.

Zinbryta and ABT-555 Laura Gault, M.D., Ph.D. Neuroscience Alzheimer’s Disease and Eric Karran, Ph.D. the Foundational Neuroscience Center

Oncology HCV Neuroscience

Immunology Elagolix Oncology Overview

Michael Severino, M.D. Despite Considerable Progress in Recent Years, Significant Unmet Medical Need Exists in Oncology

Hematologic Malignancies, 2016 Solid Tumors, 2016 U.S. Incidence (000’s) U.S. Incidence (000’s) Pancreas 53 GBM Breast Aggressive 24 249 NHL Indolent 41 NHL NSCLC 32 Colorectal 190 Ovarian 143 CLL 22 19 SCLC 34 Myeloma Prostate 30 AML 181 20 Other Other Melanoma ALL 76 470 CML 8 Renal 7 HL MDS 8 63 9 18

Sources: American Cancer Society, SEER, Kantar Health. • Growing patient population, ~21MM by 2030 – ~ 40% life-time risk of being diagnosed with cancer • ~30% of all patients diagnosed with cancer die within five years • ~80% of patients with metastatic tumors die within five years

1 Grow our strong position in hematologic malignancies

2 Establish a foundation in solid tumors

Leverage our strength in immunology to develop 3 next-generation immuno-oncology therapies

1 Grow our strong position in hematologic malignancies

2 Establish a foundation in solid tumors

Leverage our strength in immunology to develop 3 next-generation immuno-oncology therapies

These agents have the potential to transform the treatment of CLL, MCL and Waldenström’s macroglobulinemia • Monotherapy • Combination with existing therapies • Novel/novel combinations

Clinical data show strong signs of activity across a wide range of other hematologic malignancies

• NHL • NHL Imbruvica • Multiple myeloma Venclexta • Multiple myeloma • GVHD • AML

Our early pipeline provides additional opportunities based on our work in apoptosis and epigenetics

1 Grow our strong position in hematologic malignancies

2 Establish a foundation in solid tumors

Leverage our strength in immunology to develop 3 next-generation immuno-oncology therapies

Our efforts are based on:

Apoptosis Epigenetics

DNA Emerging Damage Areas in Repair Cancer Biology

ADCs with Novel Warheads

AbbVie proprietary warhead

• We are developing novel warheads that leverage our experience in apoptosis, tumor energetics, and other areas • Potent anti-tumor activity demonstrated in a range of tumor models • ADC approach circumvents mechanism-based toxicity of novel warheads in preclinical models • Target Identification • Antibody Engineering • Linker Chemistry

• AbbVie novel ADC Toxin Technology 10 mg/kg, QDx1 • Clinical Translation

Bispecific ADCs Bispecifics Can Direct Cellular Activation

Targets two antigen

• Unique properties of bispecific ADCs can be used • Different formats can be constructed to: for multiple approaches: ̶ Direct protein-protein interactions by ̶ Targeting two epitopes on single cancer target targeting different proteins on the same cell ̶ Targeting two distinct antigens on the same ̶ Activate cells in a specific setting by tumor cell targeting two targets on different cell types ̶ Targeting two antigens on different cells within the tumor microenvironment ‘cis’ Bispecific Shows Enhanced Internalization in Cancer Cells

‘trans’ ‘trans’

Effector Target cells cell Antibody to Antibody to Bispecific to epitope 1 epitope 2 epitopes 1 & 2

1 Grow our strong position in hematologic malignancies

2 Establish a foundation in solid tumors

Leverage our strength in immunology to develop 3 next-generation immuno-oncology therapies

Generation and Regulation of AbbVie Approaches Antitumor Immunity Emerging Areas: Suppressive Tumor Microenvironment e.g., anti-GARP antibodies, CD40 agonists

Emerging Biology: T Cell Agonists & T Cell Activation e.g., OX40 agonists

Disruptive Technologies: T Cell Receptor-based Biologics & Cell-based Therapies e.g., soluble TCR bispecifics

Enabling Collaborations

• Tumor microenvironment blunts the AbbVie’s bispecific platform has the potential immune response to deliver tumor-specific immune activation • Activation of CD40 restores cell- mediated immune responses tumor cell

• However, systemic toxicity has been a TumorMicroenvironment challenge for the clinical development of CD40 agonists tumor antigen CD40

AbbVie CD40 Bispecific antigen antigen presenting presenting Activated cell cell Immune Cell Tumor Cell Tumor dependent Inactive activation

tumor CD40 antigen Minimal Systemic immunity systemic toxicity against tumor

Protein 1 Protein 2

In Vitro Testing of CD40/Tumor Antigen Bispecific Formats >50 bispecific constructs prepared and screened

CD40 Tumor Antigen Binding Binding Domain Domain CD40/tumor antigen Bispecifics Multiple bispecific formats tested…

…but only the ABBV- 428 structure leads to conditional activation

ABBV-428: AbbVie’s lead CD40 Bispecific

Efficacy Toxicity

Preclinical Breast Cancer Model Toxicity

No CD40 Anti-CD40 5mg/kg No treatment Treatment Bispecific 1000 Anti-Tumor Liver Toxicity D7 D14 D21 (ALT) - + - Anti-CD40 500 CD40 Bispecific Systemic Inflammatory

Tumor Volume (mm3) Volume Tumor - + - Response 0 0 5 10 15 20 25 30 35 Days Post Inoculation

Conditional activation of CD40 Bispecific avoids toxicity by bispecific leads to efficacy of systemic CD40 agents Program is on track for human studies in 2016

Preclinical Clinical Commercial Preclinical Phase 1 Phase 2 Phase 3 Marketed

BTK IMBRUVICA CS1 VENCLEXTA BCL-2 EMPLICITI PARP veliparib PI3Kδ/ɣ duvelisib EGFR ADC ABT-414** EGFR ADC ABBV-221 cMet ADC ABBV-399 DVD ABT-165 Epigenetics ABBV-075 ADC ABBV-838 Immuno/ADC ABBV-085 Immuno ABBV-428 Immuno ABBV-927 Immuno ABBV-181 ADC ABBV-176 Hematologic malignancies Apoptosis ABBV-621 Solid tumors Heme & solid Immuno ABBV-368

** Registration-enabling studies

Preclinical Clinical Commercial Preclinical Phase 1 Phase 2 Phase 3 Marketed BTK IMBRUVICA CS1 VENCLEXTA BCL-2 EMPLICITI PARP veliparib PI3Kδ/ɣ duvelisib EGFR ADC ABT-414** DLL-3 ADC Rova-T** EGFR ADC ABBV-221 cMet ADC ABBV-399 DVD ABT-165 Epigenetics ABBV-075 ADC ABBV-838 Immuno/ADC ABBV-085 DLL-3 ADC SC-002 DPEP3 ADC SC-003 EFNA4 ADC Anti-EFNA4-calicheamicin* PTK7 ADC Anti-PTK7-auristatin* Immuno ABBV-428 Immuno ABBV-927 Immuno ABBV-181 ADC ABBV-176 Apoptosis ABBV-621 Hematologic malignancies Immuno ABBV-368 Solid tumors ADC IND-1 Heme & solid ADC IND-2 Stemcentrx ADC IND-3 ADC IND-4 * Partnered with Pfizer (PF06647263, PF06647020) ADC IND-5 ** Registration-enabling studies

Brian Slingerland Scott Dylla, Ph.D. Our Mission

Discover and Develop Cancer Therapies That Cure and Significantly Improve Survival

1. Only stem cells accumulate compounding mutations 2. Only CSC are capable of fueling continued tumor growth

Normal Tissue Tumor Mutations Stem Cell Cancer Stem Cell

Tissue/ Tumor Progenitor Hierarchy

Differentiated cells Tumor progenitors and differentiated tumor cells

1. Only stem cells accumulate compounding mutations 2. Only CSC are capable of fueling continued tumor growth 3. CSC are minimally impacted by current therapeutic regimens

Traditional Approach

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 49 • Founded in 2008 in South San Francisco, CA • Core research platforms for novel target discovery – 706 patient-derived xenograft tumor bank across major cancer subtypes

• Small Cell Lung Cancer (SCLC) • NSCLC Adenocarcinoma subtypes (3) • NSCLC Squamous cell subtypes (2) Patient Tumor PDX • NSCLC Large Cell Neuroendocrine Lung 154 • Carcinoids (typical, atypical) • Serous Colorectal 131 • Papillary Serous Ovarian 88 • Endometroid Pancreatic 80 • MMMT AML 47 • Clear Cell • Mucinous Melanoma 47 • Triple Negative (non-claudin low) • Neuroendocrine Breast 39 • Triple Negative (claudin low) Endometrial 25 • Luminal B Gastric 19 • Luminal A • Her2+ Bladder 19 Lymphoma 17 Kidney 13 Liver (HCC) 11 Other Solid Tumors 16 706

CD46+ 8.0% + . CD46+

Patient Tumor PDX Lung 154 CD46

Colorectal 131 _ Ovarian 88 CD46- . Pancreatic 80 AML 47 Melanoma 47 Breast 39 CD46+ Endometrial 25 Tumorigenic Gastric 19 Bladder 19 Lymphoma 17 Kidney 13 Liver (HCC) 11 Non- Head & Neck 5 CD46- Glioblastoma 3 Tumorigenic Other 8 706

Progenitor

Small Cell Lung Cancer Large Cell NSCLC Squamous NSCLC Triple-Negative Breast Colorectal Gastric Pancreatic Ovarian Melanoma

Dots = 1 of 59 Genes

Color = PDX of interest Bulk Tumor Bulk

Cancer Stem Cells

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 57 • Founded in 2008 in South San Francisco, CA • Core research platforms for novel target discovery – 706 patient-derived xenograft tumor bank across major cancer subtypes – Proteomic and genetic platforms for cancer stem cell and target identification

– Bioinformatics software and IT tools for target discovery and validation • Fully integrated company with 180+ employees – 110+ in target/biomarker discovery and validation – GMP antibody, chemistry and ADC manufacturing on-site (+ process sciences, QC, QA, regulatory) – 5 drugs targeting novel antigens in clinical trials (SCLC, Triple-Negative Breast, Ovarian, NSCLC) – Pipeline of CSC-associated targets in NSCLC, pancreatic, colorectal, gastric, melanoma, AML

Phase 1a Phase 1b Phase 2/3 1. DLL3-PBD ADC Small Cell Lung Cancer (SCLC); Other Neuroendocrine Tumors Rovalpituzumab Tesirine (Rova-T™) 2. PTK7-Auristatin ADC NSCLC, Breast, Ovarian (PF-06647020) 3. EFNA4-Calicheamicin ADC Triple-Negative Breast, Ovarian (PF-06647263)

4. SC-002 (Undisclosed Target) SCLC

5. SC-003 (Undisclosed Target) Ovarian

SCLC & Other Neuroendocrine Cancers Lung Cancer Statistics

Carcinoid 5%

Large Cell NEC 10%

SCLC NSCLC-Adenocarcinoma 15% 40%

NSCLC-Squamous 30%

American Cancer Society

All Lung Cancer SCLC Newly Diagnosed – US, EU, Japan 540,000 81,000 Newly Diagnosed – Worldwide 1,825,000 274,000 5-Year Survival 18% 3%

Rova-T Phase 1 Trial = 74 SCLC Patients

1st Line SCLC: Carbo/Cisplatin + Etoposide 3rd Line SCLC ~70% Response Rate No Approved Drug

92% G3+ Toxicities Tumor Volume Tumor 2nd Line SCLC: Topotecan 7-17% Response Rate Duration of Response 89% G3+ Toxicities ~3 months

Time

Normal Lung Stem Cell

Common Progenitor Cell Borges (1997) Nature 386:852 Li (2012) Am J. Respir Cell Mol Biol 47:768 ASCL1 Notch Kunnimalaiyaan (2007) Oncologist 12:535 Morimoto (2012) Development 139:4365 Committed Progenitor Cells

Mature Mature Epithelial Cell Neuroendocrine Cell

Precancerous Lung Stem Cell

p53-/-

-/- -/- Meuwissen (2003) Cancer Cell 4:181 p53 RB1 Cancer Stem Cell Moreira (2010) Mod Pathol 23:889 (cell of origin) ASCL1 Tumor-Initiating Cells Notch (TICs)

Committed Tumor Progenitor Cell Progenitor Cells

Mature Mature Epithelial Cell Neuroendocrine Tumor Cell

RNA Seq

100

0.1

RPKM_Transcript

0.01

NL Tissues

• Normally expressed during development and localized to Golgi intracellular compartment

• Interacts with and inhibits Notch1 localization to the cell surface

• Mediates DLL1 intracellular retention in concert with LFNG, inhibiting Notch activation in trans

Geffers et al. (2007) J Cell Biol 178:465. Chapman et al. (2011) Human Mol Genetics 20:905. Serth et al. (2015) PLoS ONE 10:e0123776.

Kume T. (2009) Journal of Angiogenesis Research 1:8

Precancerous Lung Stem Cell

p53-/-

10 8 SCLC -/- -/- LCNEC p53 RB1 Cancer Stem Cell 10 7

ASCL1 10 6 DLL3 Pearson r2= 0.66 Notch

ASCL1 P < 0.0001 10 5 Committed 10 0 Tumor Progenitor Cell Progenitor Cells 10 -1 10 -2 10 5 10 6 10 7 10 8 10 9 DLL3

Mature Mature Epithelial Cell Neuroendocrine Tumor Cell

George J. et al. (2015) Nature 524:47-53.

Precancerous Lung Stem Cell

p53-/-

p53-/- RB1-/- Cancer Stem Cell

ASCL1 DLL3 Notch

Committed Tumor Progenitor Cell Progenitor Cells DLL3 ~80%

Mature Mature Epithelial Cell Neuroendocrine Tumor Cell

2.5 DLL1 SCLC PDX DLL3 Immunohistochemistry 2.0 DLL4 300 1.5

1.0

0.5 200

Absorbance (A450) 0.0 0.001 0.01 0.1 1 10 DLL3 [Ab], (nM)

SCLC SCLC 100

(Inten sity x % C e lls P ositive)

M em branous H-Score

0 Norm Tissues Naive SCLC R/R SCLC Courtesy of Courtesy of Pierre Massion Afshin Dowlati 20µm (Vanderbilt) (Case Western U.) Saunders et al. (2015) Sci Transl Med 302ra136.

= DLL3

Xu and Esko, Nat Chem Biol 2009

= DLL3

Drug-to-Antibody Ratio (DAR) = 2

8 PEG Spacer Val-Ala SC16 Self-Immolating Group

Maleimide Conjugation PBD Dimer Toxin (D6.5)

= DLL3

Rova-T (SC16LD6.5)

= DLL3

Rova-T (SC16LD6.5)

= DLL3

Rova-T (SC16LD6.5)

n = 5 mice/group

300

250

200

150

100

M em branous H -S core Rova-T 0 (1 mg/kg) Naive SCLC

Dosing LU95 n = 7 mice/group IgG 3 Control 1:61 1:62

hIgG1LD6.5 (1 mpk) 2 1:105 Cisplatin + Etoposide (5 mpk x 1 + 8 mpk Qdx3) 1

(% of Tumor)

TIC Frequency

1:13,004 0

C/E Rova-T Naive (1 mpk) IgGLD6.5 SC16LD6.5

Cisplatin/Etoposide Single Agent Rova-T DLL3 2 5 0 (5 mpk x 1, 8 mpk Qdx3) (1 mpk q4d x 3) Expression S C L C L C N E C

%TGI TTP (days) %TGI TTP (days) IHC H-Score 2 0 0

LU102 97% 28 100% > 181 171

e r

LU95 56% 2 100% > 168 104 o 1 5 0

c S

LU117 98% 21 100% > 167 42 -

X 1 0 0

LU149 90% 18 100% > 161 201 D P LU129 87% 52 100% > 159 141 5 0 LU111 84% 22 100% > 140 137 LU37 60% 4 100% > 132 221 0 LU64 78% 12 100% > 119 144 0 5 0 1 0 0 1 5 0 2 0 0 T T P ( d a y s ) LU124 83% 19 88% 47 60 Number of XY Pairs 13 LU73 85% 28 75% 47 56 Pearson r 0.7296 LU80 75% 15 75% 37 9 95% confidence interval 0.2985 to 0.9134 P value (two-tailed) 0.0046 LU86 26% 0 95% 32 42 P value summary ** Is the correlation significant? (alpha=0.05) Yes LU100 100% 63 0% 0 0 R square 0.5323 Avg 78% 22 87% > 107

80 Expression % of SCLC High 71% 60 Intermediate 11% Low 18% 40 Unknown 20

(RECIST) -20

Best Best Response

-40 % Change in Tumor Diameter Tumor in Change %

-60 Presented at ESMO/ECC’15 - Vienna -80

40 • 44% ORR (CR/PR) • 78% CBR (CR/PR/SD)

-20

(RECIST)

Best Best Response -40

-60 % Change in Tumor Diameter Tumor in Change % Presented at ESMO/ECC’15 - Vienna -80 DLL3+ = H-score ≥ 180 on scale of 300 ^3 Pts whose target lesions were noted as SD or better by RECIST had clinical progression

nd 40 2 Line: 44% ORR, 81% CBR (Topotecan = 7-17%) 3rd Line: 45% ORR, 73% CBR (No Approved Drug) 20

- 2 0

(RECIST)

B e st -R 4 e 0 sponse

- 6 0 % Change in Tumor Diameter Tumor in Change % Presented at ESMO/ECC’15 - Vienna - 8 0 DLL3+ = H-score ≥ 180 on scale of 300

Dose #1 Dose #2 Dose #3 0.3 mpk 0.3 mpk 0.3 mpk Residual Tumor Resected 100 (Adrenalectomy)

PR -37% PR PR -51%,

(RECIST) -49% PET Scan SUV Negative 60 PR -54%

% S tarting Tum or D iam eter

40 0 60 120 180 240 300 360 D a y

“Upon pathology review, there are only isolated clusters of viable tumor with an estimated >95% treatment effect.”

Dose #1 Dose #2 Dose #3 0.3 mpk 0.3 mpk 0.3 mpk Residual Tumor Day 556 Resected (3/3/16)

1 0 0 (Adrenalectomy)

a i

8 0

)

o T

S PR

I u

C -37%

T E

PR PR -51%,

R g

( PET Scan

n -49% i t SUV Negative

r 6 0

a t

S PR

% -54%

4 0

0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0 4 2 0 4 8 0 5 4 0 6 0 0

D a y

Doses #1 & 2 0.2 mg/kg Dose #3 0.1 mg/kg Day 665 (4/18/16)

e 1 2 0 m

u PET/CT Scans l

(No abnormal SUV) o

1 0 0

r SD o

) +13%

T m

S 8 0

n R

i 6 0

(

t S

4 0 %

2 0 0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0 4 2 0 4 8 0 5 4 0 6 0 0 6 6 0 7 2 0

D a y

Historical Rova-T (n = 120) DLL3Hi Simos’14 (n = 27) ORR 18% 44% CBR 51% 78% mOS (Mo) 4.7 TBR - Sunday 1 Year OS 12% TBR - Sunday

1st Line SCLC: TRINITY Carbo/Cisplatin + Etoposide 3rd Line SCLC ~70% Response Rate No Approved Drug

91% G3+ Toxicities Tumor Burden Tumor

2nd Line SCLC: Topotecan 17% Response Rate Duration of Response 89% G3+ Toxicities ~ 3 months

Time

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 88 Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 89 28 Sites in the U.S. and Europe Currently Enrolling TRINITY

1st Line SCLC: TRINITY Carbo/Cisplatin + Etoposide 3rd Line SCLC ~70% Response Rate No Approved Drug

91% G3+ Toxicities Tumor Burden Tumor

2nd Line SCLC: Topotecan 17% Response Rate Duration of Response 89% G3+ Toxicities ~ 3 months

Time

Nivo Nivo+Ipi (2L+) (2L+) (n = 80) (n = 47) ORR 13% 31% CBR 29% 53% mOS (Mo) *3.6 *7.8 *Data to be updated Saturday morning (ASCO’16)

BMS, Immuno-Oncology, 201x

Metastatic Melanoma NE Prostate NE Pancreatic

NE Colorectal Medullary Thyroid Glioblastoma

Abstract 11611, Poster Board: #308 – Tumor Biology, Hall A, 1-4 PM, Jun 6th

2016 2017 2018 Purpose 3rd Line DLL3+ SCLC Single-Arm Pivotal (TRINITY) AA in US; CA in EU

All SCLC DLL3 +/- QT; DLL3 agnostic

1st Line SCLC Phase I Pre-pivotal 1L

Basket Study (8 arms) Phase I Indication Expansion

Checkpoint Inhibitor Combo Phase I 1L Rx Selection

1st Line Maintenance SCLC Randomized Phase III Confirmatory

Japan Phase I CA in JP

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 95 Other Clinical & Pipeline Drugs Other Clinical & Pipeline Drugs Clinical Drug #2: αPTK7-Auristatin (PF-06647020) Non-Small Cell Lung, Breast and Ovarian Cancer Preclinical Efficacy with PTK7-ADC

Ovarian OV55

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 98 Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 99 PF-06647020 Is Efficacious as a Single Agent in Humans

Breast cancer ≥ 2.1 mg/kg Data cut-off as of July 31, 2015 Ovarian cancer ≥ 2.1 mg/kg

Tolcher AW et al. ESMO’15 - Vienna

Baseline After 2 cycles PR After 4 cycles CR

• 52 yo woman with advanced ovarian cancer (serous papillary carcinoma) previously treated with multiple lines of chemotherapies including carboplatin/taxol, cisplatin/gemcitabine, carboplatin/pegylated liposomal doxorubicin, and nab paclitaxel (the last immediate therapy) Progressive Disease • Patient received PF-06647020 at 2.1 mg/kg IV, q3w Tolcher AW et al. ESMO’15 - Vienna • The CR was confirmed, and she has been in the study for 6 months

Tolcher AW et al. ESMO’15 - Vienna

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Total n % n % n % n % n % n % Any AEs 5 (25.0) 6 (30.0) 4 (20.0) 0 (0.0) 0 (0.0) 15 (75.0) Fatigue 4 (20.0) 2 (10.0) 1 (5.0) 0 (0.0) 0 (0.0) 7 (35.0) Headache 0 0.0) 6 (30.0) 1 (5.0) 0 (0.0) 0 (0.0) 7 (35.0) Nausea 5 (25.0) 2 (10.0) 0 (0.0) 0 (0.0) 0 (0.0) 7 (35.0) Alopecia 2 (10.0) 3 (15.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (25.0) Vomiting 1 5.0) 4 (20.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (25.0) Chills 3 (15.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (15.0) Diarrhea 2 (10.0) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (15.0) Neutropenia 0 0.0) 1 (5.0) 2 (10.5) 0 (0.0) 0 (0.0) 3 (15.0) Pruritus 2 (10.0) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (15.0) Rash maculo-pap 2 (10.0) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (15.0) Hypomagnesaemia 2 (10.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (10.0) Myalgia 1 (5.0) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (10.0) Data cut-off as of July 31, 2015 Tolcher AW et al. ESMO’15 - Vienna

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 103 Other Clinical & Pipeline Drugs Clinical Drug #3: αEFNA4-Calicheamicin (PF-06647263) Triple-Negative Breast and Ovarian Cancer 90% of TNBC PDX Express and Respond to EFNA4-ADC

PDX-Breast 5 Dosing (High Expresser) %TGI TTP Tumor (Subtype) Vehicle (0.3 mpk) (0.3 mpk) IgG Control ADC BR5 (Basal) 100% 172+ 1.5 mpk Doxorubicin BR31 (Basal) 100% 147 ~90% BR56 (Basal) 98% 63 n = 5 mice/group TNBC BR13 (Bas/Lum) 99% 97 BR22 (Bas/Lum) 90% 43 BR25 (Claudin 27% -- low) BR64 (Claudin EFNA4-ADC 0% -- low) BR17 (Her2+) 0% --

Breast cancer ≥ 0.01 mg/kg QW or 0.05 Q3W Ovarian cancer

Hong DS et al. ASCO 2015 poster

(TNBC)

Hong DS et al. ASCO 2015 poster

LumB Target SCLC TNBC OV MEL NSCLC PA CR GA AML BR

DLL3

PTK7

EFNA4

SC-002

SC-003

SC-004

SC-006

Target 8

Target 9

Target 10

LumB Target SCLC TNBC OV MEL NSCLC PA CR GA AML BR

DLL3

PTK7

EFNA4

SC-002

SC-003

IND #6

IND # 7

IND # 8

IND # 9

IND # 10

Patient #1 Patient #2

Target 1 Target Target 2 Target

Target 1 ADC Target 2 ADC

• 3 of 3 first clinical drugs showing single-agent efficacy at tolerated doses

• All 3 targeting antigens (DLL3, PTK7, EFNA4) never before pursued clinically

• Discovery platform unveiling additional novel targets (ADC, CAR-T/NK/TCR, SM)

• 2016 Milestones

– TRINITY pivotal study initiated

• Continue to ensure rapid enrollment

– Initiate 1st line SCLC induction studies for regimen selection

– Initiate 1st line SCLC maintenance confirmatory study by 4Q’16/1Q’17

– Initiate neuroendocrine basket study

– Initiate checkpoint inhibitor combo studies

Danelle James, M.D., M.S. Despite Efficacy of Current Standard of Care, Unmet Need Remains in CLL and NHL

< 55 years of age at diagnosis 100

P < 0.001 80

60 B-cell NHL New Cases and Deaths, U.S., 2016

40 Surviving (%) Surviving

20 Observed CLL 72,580 Age-matched population 0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

65-74 years of age at diagnosis 20,150 100 P < 0.001 80

60 Incidence Deaths 40

Surviving (%) Surviving Cancer Facts and Figures 2016 20 Observed CLL Age-matched population 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years Shanafelt et al, Cancer, 2010;116:4777-4787

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 114 From Target Validation to Front-line Indication: Rapid Development of the First Inhibitor of Bruton Tyrosine Kinase (BTK), Ibrutinib

1952 Colonel Bruton described a genetic disorder, agammaglobulinemia

1993 2013 2014 2015 BTK gene was cloned Approved for Approved for 2014 Approved for and characterized 2009 First human MCL patients CLL patients Approved for WM patients treated who received who received CLL patients Oct 2015 FDA Approval with at least 1 with deletion in SLL at least 1 sNDA Treatment ibrutinib prior therapy 17p prior therapy Naïve submitted May 2016 2005 2010 2014 2015 2016 2005 2013 2013 2014 Mar 2016 CLL & MCL First synthesis NDA submitted RESONATE™ FDA approval top-line data Dec 2015 of ibrutinib for two R/R B-cell Data published for front-line. published in RESONATE-2 (PCI-32765) malignancy in NEJM Extremely rapid NEJM Data published indications: Jan 2015 development in NEJM MCL & CLL Treon paper on of First-in-Class Three Waldenström’s BTK Inhibitor Breakthrough published in Therapy NEJM Designations Received

RESONATE-2™ UK CLL NCRN iLLUMINATE Alliance 041202 CLL 12

Study PCYC-1115 & ECOG 1912 PCYC-1130

Age ≥ 65 Age ≥ 65 Watch Age < 70 Age ≥ 65 or

Patient Patient & Wait

Population comorbidities

Ibr Ibr Ibr-Ritux or Ibr-obinutuz Ibr vs vs Ibr-Ritux vs vs Regimen Chl FCR vs Chl-obinutuz placebo BR

FCR – fludarabine, cyclophosphamide, rituximab. Ibr – ibrutinib, ritux- rituximab. BR – bendamustine, rituximab. Obinutuz – obinutuzumab. Chl – Chlorambucil

NEJM: Imbruvica Front-Line CLL Data (RESONATE-2)

 NCCN category 1 for key front-line patient segments in addition to all previously treated segments

 Full FDA approval for CLL/SLL (all lines of therapy and all genetic subgroups)

 EMEA review ongoing for first-line indication, positive opinion from CHMP received April 2016

• 91% reduction in risk of progression or death with Imbruvica • 84% reduction in the risk of death compared to chlorambucil – With a median of 28.1 months of follow up and crossover of 41% of chorambucil patients a statistically significant 54% reduction in risk of death for Imbruvica arm

USPI Imbruvica May 2016 NEJM Burger 2016

RESONATE-2™ UK CLL NCRN iLLUMINATE Alliance 041202 CLL 12

Study PCYC-1115 & ECOG 1912 PCYC-1130

Age ≥ 65 Age ≥ 65 Watch Age < 70 Age ≥ 65 or

Patient Patient & Wait

Population comorbidities

Ibr Ibr Ibr-Ritux or Ibr-obinutuz Ibr vs vs Ibr-Ritux vs vs Regimen Chl FCR vs Chl-obinutuz placebo BR

We anticipate data from studies to read out from 2017 - 2019

FCR – fludarabine, cyclophosphamide, rituximab. Ibr – ibrutinib, ritux- rituximab. BR – bendamustine, rituximab. Obinutuz – obinutuzumab. Chl – Chlorambucil

Strong expression of BCL-2 observed throughout Imbruvica treatment

BCL2 2.0 Expression (median fluorescence intensity) P=0.5 100000 100000 1.5

1000010000

fluorescence) fluorescence) 1.0

old old Change

F 2 2

10001000 - 0.5 BCL

100 0.0 100 Screen Baseline 4hrs 24hr Wk1 Wk2 M1 M2 M6 0 4 0 4 0 2 0 4 12 0 2 4 0 4 12 Expression (median Expression Screen Baseline 4hrs24hrs Wk1 Wk2 M1 M2 M3 146A 775 808 146J 327 011 TN / RR n= 20/20 19/20 14/5 *Rawston EHA 2015 *Cervantes-Gomez Clin Can Res. Epub Mar 31, 2015

Leukemia cells from patients treated with Imbruvica are highly sensitive to apoptosis with Venclexta 100 146A 775 595 80 011 Serial samples of CLL cells obtained

V/PI V/PI 728 60 627 before and 2, 4, or 12 weeks after the 226 146J start of Imbruvica showed no 40 327 reduction in BCL-2 protein, and

270 Positive

Annexin 20 sensitivity to Venclexta % % 0 10 15 Venclexta Benda *Cervantes-Gomez Clin Can Res. Epub Mar 31, 2015 nmol/L mol/L

CLL13 –OBVIOUS Study GCLLSG Phase 3 - TN CLL Ibr + Ve + Obinutuz vs. Ve + Obinutuz vs. Ve + Ritux vs. FCR/BR n = 920

CLL13b GCLLSG Phase 2 TN del 17p CLL Ibr + Ve + Obinutuz n = 60

CLARITY Study Phase 2 R/R CLL Ibr + Ve n = 100

PCYC-1142 Phase 2 TN CLL patients <70yrs Ibr + Ve n = 150

OAsIs Study MCL Phase 1 R/R MCL Ibr + Obinutuz + Ve n = 33

AIM Study Phase 2 TN & R/R MCL Ibr + Ve n = 24

FCR – fludarabine, cyclophosphamide, rituximab. Ibr – ibrutinib, ritux- rituximab. BR – bendamustine, rituximab. Obinutuz – obinutuzumab. Ve -Venteoclax

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 120 The Combination of Imbruvica and Venclexta Rapidly Achieves CR in Patients with R/R MCL: Preliminary Results of the Phase 2 AIM Study

ve ramp up Objective: to Determine Complete Response Rate

Patients • Median age: 72 y 8 pts enrolled; 24 planned (53-77); median prior Tx: 2 (1-7); high MIPI Efficacy score: 63% • Response after 4-week ibr induction (n=5 evaluable): 2 PR, 2 SD, 1 PD Safety • Response after 4 mo (n=3 evaluable): 2 CR , 1 PR • Full Venclexta dose (400 mg) reached in all 4 pts who entered ramp-up with no TLS – CR: normalization of PET ± endoscopy, and complete clearance of previous • Most common AEs (all Gr 1-2): nausea marrow involvement, including flow (n=4), diarrhea (2), oral candidiasis (2) cytometry at >10-4 sensitivity

Early experience with Imbruvica + Venclexta shows no unexpected safety signals with promising efficacy

*ASCO abstract 7519, Tam 2016

Molecule & Program / Indication Phase 2 Phase 3 Approved Imbruvica (PCI-32765): Bruton’s tyrosine kinase (BTK) inhibitor for Oncology * Chronic lymphocytic leukemia Small Lymphocytic Lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Multiple myeloma Follicular lymphoma Marginal zone Waldenström’s macroglobulinemia Acute myeloid leukemia Solid Tumor PD1/PDL1 combinations in solid tumor and NHL Imbruvica (PCI-32765): Bruton’s tyrosine kinase (BTK) inhibitor non-Oncology Chronic GVHD

*Janssen Biotech: global partnership

Single Agent Imbruvica Imbruvica + R-CHOP in Treatment-Naïve DLBCL Patients 100 CR 80 PR 100

60 41% ORR 100% 12/29 80 (91% CR, 9% PR) 40 4 non - GCB pts PR 5% 60 (all CR) 20 1/20 14 GCB pts 40 91% CR (86% CR, 14% PR) Proportion of Patients (%) Patients of Proportion 0

ABC DLBCL GCB DLBCL 20 CR Patients (%) Patients

Proportion of of Proportion PR Overall response and depth of response was (%) Patients of Proportion 9% PR significantly better with single-agent ibrutinib 0 in patients with ABC subtype compared to Efficacy Evaluable Patients GCB subtype. (N=22)

de Vos et al. 2013. Younes et al. ASH 2013.

Ongoing Phase 3 study, PHOENIX, evaluating Imbruvica in combination with R-CHOP for the first-line treatment of Non-GCB DLBCL in >800 patients

ABC – activated B-cell. GCB – germinal center B-cell. R-CHOP – rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.

Maximum Tumor Reduction Best Response 100 100 CR PR SD 90 82% 80 70 30% 50 60 50 40 0 30 52% 20 10

-50 0

CR Improvement from Baseline SPD Baseline from Improvement

% % PR N=60 * -100 Fowler ASH 2015 • ORR 82% in all treated *Response recorded in database is SD; unresolved query patients (49 of 60) Abbreviations: CR, complete response; PR, partial response; SD, stable disease; SPD, sum of the products of the greatest perpendicular diameters • Median duration of Imbruvica treatment: 12.55 months

Ongoing pivotal studies in indolent lymphoma to read out 2016–2018

HELIOS CLL/SLL - PFS • HELIOS the first of three Phase 3 studies in the Imbruvica program Imbruvica-BR – Combination data added to Ibrutinib + BR (Median PFS: NR) USPI and approval of SLL May 2016 • SELENE, a fully enrolled Phase 3 study, evaluating Imbruvica+BR vs Placebo + BR (Median PFS: 13.3 mos) placebo-BR in previously treated FL and MZL • SHINE, a fully enrolled Phase 3 study, assessing Imbruvica+BR vs HR: 0.203 (95% CI, 0.15 – 0.28) P < 0.0001 Median follow-up: 17.02 months placebo-BR as first-line therapy for MCL Fraser et al, iwCLL, 2015.

Human Pancreatic Adenocarcinoma Imbruvica Prolongs Survival in Preclinical Models

P = 0.002

Human Spleen Survival Percent Murine Weeks Prominent phospho- BTK in CD20+, CD11b+ and CD64+ (FcγR1) cells infiltrating human PDAC, but p = 0.04 NOT spleen

Murine Percent Survival Percent Murine 126 Gunderson A et al. BTK-dependent immune cell crosstalk drives pancreas cancer. Weeks Cancer Discov, 2015 Daniel Massó-Vallés et al. Cancer Res 2015;75:1675-1681

Three ongoing – enrolling company-sponsored clinical trials evaluating Imbruvica in multiple different solid tumors • Two evaluating Imbruvica in combination with standard of care (chemotherapy or targeted agents) – One randomized and one basket study • One basket study evaluating Imbruvica in combination with checkpoint inhibitor

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 126 Imbruvica, Targeting both B and T Cells Combats the Multifactorial Pathology of cGVHD Leading to Responses in High-Risk Patients

Imbruvica Inhibition: Self-reactive Deposit Within Clinical Data of Imbruvica Antibody Healthy Tissues Complexes & Blood Vessels in high-risk cGVHD Self-reactive B-Cells Best Response per NIH criteria 100% (n=22)

cGVHD 80% immune 55% Tfh Cells 60% Pathology 5% Kill Healthy Cells 40% & Tissues Overproduction of Th17 Cells 20% 50% CR Self-reactive T and PR B-cells from Donor- Drived Bone 0% Marrow Th2 Cells Miklos et. al European Society for Blood and Marrow Transplantation 2016

cGVHD is a common complication of stem cell transplant with substantial morbidity – where there are no approved therapies representing a significant unmet medical need

2016 2017 2018 2019 2020

 (RESONATE-2) 1L CLL (approval)  (Alliance-CTEP) P3, 1L CLL

CLL/SLL  (HELIOS) R/R CLL/SLL  (iLLUMINATE) P3, 1L CLL/SLL (ibr+G vs CG) * (label expansion & (CLL13) P3, 1L CLL (+GVe) SLL approval) +BR)  (PCYC-1126e) P3, 1L CLL *

 (PCYC-1135) PDL1, solid tumor  (RESOLVE) P2/3, Pancreas * Solid Tumor  (PCYC-1128) P1b/2, solid tumor (I+ SOC) *

 (DAWN) P2, R/R FL  (PHOENIX) P3, ibr-RCHOP 1L DLBCL *  (PCYC-1121) P2, MZL  (iNNOVATE) P3, 1L & R/R WM * NHL  (SHINE) P3, 1L MCL *  (SELENE) P3, R/R FL/MZL *

 (iMMERGE) P2, R/R MM ibr +pom* MM  (iMMPACT) P2 ibr+vel R/R MM

cGVHD  (PCYC-1129) cGVHD

* Approximate dates. Timing for some studies will be based on event rates and interim analysis triggers R=Rituxan; G=Gazyva; BR=bendamustine/Rituxan; CG=chlorambucil/Gazyva; GI=Gazyva/Imbruvica; RCHOP=Rituxan, cyclcophosphamide, doxorubicin, vincristine, prednisone; Vel=velcade; Dex=dexamethasone; pom=pomalidomide

Gary Gordon, M.D., Ph.D. AbbVie Has Pioneered the Field of BCL-2 Inhibition

Venclexta Mechanism of Action

• Ability to evade apoptosis (programmed cell death) is a hallmark of cancer • Increased production of BCL-2 proteins is a key mechanism for preventing the apoptotic process from occurring • Venclexta binds selectively to BCL-2 proteins initiating a cascade of events leading to rapid cell death

Restoration of apoptosis through BCL-2 Inhibition

Pro-apoptotic Venclexta BCL-2 protein BCL-2

Apoptosis Cancer Cell Survival initiation

Pro-apoptotic BIM protein BAX

BAK Cancer Cell Death BAX

Activation of caspases Cytochrome c

BCL-2 overexpression allows Venclexta binds selectively to BCL-2, cancer cells to evade apoptosis by freeing pro-apoptotic proteins that initiate sequestering pro-apoptotic proteins. programmed cell death (apoptosis).

Combination (study name) Indication Ph 1 Ph 2 Ph 3 +Rituxan (MURANO) r/r CLL +Gazyva (CLL14) CLL monotherapy r/r CLL 17p * CLL monotherapy r/r CLL after BCRi * +Rituxan r/r CLL & SLL * +BR r/r CLL & CLL +Gazyva r/r CLL & CLL +Gazyva/Imbruvica (CLL13) (a) 1L CLL +Rituxan vs BR (CONTRALTO) r/r FL +R-CHOP vs R-CHOP (CAVALLI) 1L DLBCL * NHL +BR r/r NHL monotherapy r/r CLL & r/r NHL +Gazyva/polatuzumab DLBCL & FL monotherapy r/r MM * MM +bortezomib/dex r/r MM * +bortezomib/dex (a) r/r MM +dec / +aza (a) AML monotherapy AML AML +dec / +aza AML * +Ara-C AML *

(a) Starting H2:2016. Supported by three breakthrough therapy designations * Data to be presented at ASCO.

(a) Starting H2:2016. Supported by three breakthrough therapy designations

RESPONSE RATES IN RELAPSED CLL • FDA approved for r/r 17p MRD = 55% deletion CLL (bone marrow) MRD = 3% IIT population, N=49 100% (bone marrow & • Active in broader CLL peripheral blood) 86% population 80% 79% 80% 7% • Next anticipated indication: 20% combination with rituximab 60% 47%

• Minimal residual disease 40% 73% (MRD) negativity – no 59%

detectable CLL cells in the 20% 39%

patients’ bone marrow Percentage of patients responding patients of Percentage 0% Venclexta 17pdel (a) Venclexta (b) Venclexta + (c) Rituxan  Objective response rate (ORR)  Complete responses (CR) Davids et al. ASCO 2016 (Abstracts # 7527, 7528). « Next step: Phase 3 in 1L CLL »  Partial responses (PR) Update June 6, 8:00-11:30 (Hall A).

(a) Venclexta package insert. (b) Roberts et al, NEJM 2016. (c) Ma et al. ASH 2015.

BCRi – inhibitor of B-cell receptor signaling pathway. RESPONSES AT 24 WEEKS ON VENCLEXTA AFTER BCRi

 Objective response rate (ORR) • Progression can be rapid  Complete responses (CR)  Partial responses (PR) when B receptor pathway 70% 61% inhibitors fail 60% 8% 50% • Treatment options are 50% limited and prognosis is poor 40% 30% 53% 50% • Alternatives are required to 20% meet this unmet need 10% 0%

Percentage of patients responding patients of Percentage Imbruvica Zydelig / CD20 progression progression (N=38) (N=10)

Stable disease: 26% and 40% in Imbruvica and Zydelig cohorts, Jones et al. ASCO 2016 (Abstract #7519). respectively. Update June 6, 1:15-2:45 (E354b).

O’Brien et al. ASCO 2016 (Abstract #7520) « Next step: Phase 2 readout in 2017 »

Combination (study name) Indication Ph 1 Ph 2 Ph 3 +Rituxan (MURANO) r/r CLL +Gazyva (CLL14) CLL monotherapy r/r CLL 17p monotherapy r/r CLL after BCRi CLL +Rituxan r/r CLL & SLL +BR r/r CLL & CLL +Gazyva r/r CLL & CLL +Gazyva/Imbruvica (CLL13) (a) 1L CLL +Rituxan vs BR (CONTRALTO) r/r FL +R-CHOP vs R-CHOP (CAVALLI) 1L DLBCL * NHL +BR r/r NHL monotherapy r/r CLL & r/r NHL +Gazyva/polatuzumab DLBCL & FL monotherapy r/r MM * MM +bortezomib/dex r/r MM * +bortezomib/dex (a) r/r MM +dec / +aza (a) AML monotherapy AML AML +dec / +aza AML * +Ara-C AML *

(a) Starting H2:2016. Supported by three breakthrough therapy designations

U.S. Epidemiology Disease • Median age at diagnosis: 66 • Multiple subtypes: aggressive (DLBCL, MCL) and indolent (FL, CLL/SLL) 3L+ 25,461 • DLBCL 50% cure; FL median PFS 70 months

2L 41,230 Standard of Care 72,580 • R-CHOP, BR • Rituxan • Imbruvica (MCL) 1L 69,775

Unmet Needs • Curative treatment (FL) Incidence Treated Population • More efficacious therapies for - 20,150 deaths annually - relapsed/refractory aggressive disease (DLBCL)

Sources: American Cancer Society, SEER, Kantar Health.

OBJECTIVE RESPONSES

 Objective response rate (ORR)  Complete responses (CR) 100%  Partial responses (PR) 100%

80% 75% 67% 21% 60%

100% 44% 38% 40% 13% 67% 14% 22% 54% 20% 10% 31% 24% Percentage of patients responding patients of Percentage 12% 0% MZL WM DLBCL FL MCL All patients (N=3) (N=4) (N=41) (N=29) (N=28) (N=106)

Gerecitano et al. ASH 2015. « Next step: Phase 2 readouts (1L DLBCL, CAVALLI* and r/r FL, CONTRALTO) in 2017 » * Zelenz et al. ASCO 2016 (Abstract #7566). Update June 6, 8:00-11:30 (Hall A).

U.S. Epidemiology Disease • Median age at diagnosis: 69 • Five-year survival: 48% 3L+ 13,611 30,330 Standard of Care

2L 9,791 • Velcade/Revlimid/Dex • Pomalyst, Kyprolis • New agents: 1L 18,444 Empliciti, Darzalex, Ninlaro

Unmet Needs

Incidence Treated Population • Curative treatment

- 12,650 deaths annually - • Therapies for relapse/refractory patients

Sources: American Cancer Society, SEER, Kantar Health.

Strong mechanistic rationale for combination of Venclexta with the proteasome inhibitor bortezomib, which is a cornerstone therapy in multiple myeloma

• Overall response rates in r/r MM  CR+sCR 100%  VGPR are superior to historical Velcade 100%   PR data and encouraging compared to novel regimens 34% 80% 71% • Deep responses (VGPR or CR)  Historical 12% in half of these patients 60% benchmark* (ORR) bortez/dex=63% • >80% response rates in patients 24% who received one to three prior 40% 50% lines of therapy 17% 20% 35%  17% 17% CR=complete response; sCR=stringent complete 0% response; VGPR=very good partial response; Bortezomib Bortezomib Bortezomib PR=partial response; bortez/dex=bortezomib, naïve sensitive refractory dexamethasone. (N=6) (N=17) (N=18)

Moreau et al. ASCO 2016 (Abstract #8011). Update June 7, 9:45-11:15 (E354b).

* Bortezomib naïve, sensitive, 1-3 prior treatments « Next step: Phase 3 trial start (r/r MM) in H2:16 » (ENDEAVOR trial. Dimepoulos et al. Lancet Oncol 2016)

Disease U.S. Epidemiology • Median age at diagnosis: 67 • Five-year survival: 27% (<5% in pts 65+ yrs.) 19,950 3L+ 1,945 • No improvements in treatment in 25 yrs.

2L 5,251 Standard of Care • Younger patients, high-dose intensive chemo (cytarabine/anthracycline) • Patients with co-morbidities (low-dose cytarabine, hypomethylators) 1L 15,591 • Stem-cell transplant

Unmet Needs • Stem-cell transplant only curative therapy Incidence Treated Population • Improved options for patients unable to tolerate intensive therapy - 10,430 deaths annually - • Improved survival for relapsed/refractory setting Sources: American Cancer Society, SEER, Kantar Health.

OBJECTIVE RESPONSES

Venclexta +  Objective response Venclexta + rate (ORR) 100% decitabine or LoDAC  CR+CRi azacitadine  Partial responses (PR)

80% 76%

60%

71% 44%

40%

44% Historical benchmarks 20% (CR+CRi)

azacitidne = 28% responding patients of Percentage decitabine = 26% 0% 5% Historical benchmark (N=34) (N=18) (CR+CRi) Dombret et al. Blood 2015. LoDAC = 11% Kantarjian et al. JCO 2012. Pollyea et al. ASCO 2016 (Abstract #7009). Lin et al. ASCO 2016 (Abstract #7007). Update June 4, 3:00-6:00 (Arie Crown Theatre) and June 6, 11:30-12:45 (E354b). Kantarjian et al. JCO 2012. CR = complete remission. CRi = complete remission with incomplete blood count recovery.

« Next step: Phase 3 trial start in H2:2016 »

2016 2017 2018 2019 2020

 Three CLL readouts  • P1, r/r CLL & SLL (+ R) P3, r/r CLL (+R)  • P1, r/r CLL & SLL (+ BR) (MURANO) P3, CLL (+G) CLL (CLL14) • P1, r/r CLL & SLL (+ G)   P3, 1L CLL (+GI) P2, r/r CLL (CLL13) after BRCi   Three NHL readouts NHL P1, r/r CLL & r/r NHL • P2, r/r FL (+R vs BR) (CONTRALTO) • P2,1L DLBCL (+RCHOP vs RCHOP) (CAVALLI) • P1, r/r NHL (+BR)

 MM P1, r/r MM   P3, r/r MM P1, r/r MM (+bortez/dex) (+bortez/dex)

 P1, AML AML (+dec, +aza)   P3, AML P1, AML (+Ara-C) * Approximate dates. Timing for some studies will be based on event rates and interim analysis triggers R=Rituxan; G=Gazyva; BR=bendamustine/Rituxan; GI=Gazyva/Imbruvica; RCHOP=Rituxan, cyclcophosphamide, doxorubicin, vincristine, prednisone; Bortez=bortezomib; Dex=dexamethasone; Dec=decitabine; Aza=azacitidine; Ara-C=cytarabine.

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 143 Veliparib and ABT-414 Veliparib Activity in Phase 2 Trials Provides Evidence for: 1) Monotherapy Efficacy; and 2) Synergy with Chemotherapy

Veliparib has demonstrated single-agent activity Veliparib inhibits PARPs 1 and 2 which are 1 in BRCA-deficient tumors

critical nuclear enzymes for DNA damage repair Population (study) N ORR (%) Recurrent ovarian cancer 50 26 (GOG 0280) Recurrent ovarian cancer 39 40 (CTEP 8282) Recurrent ovarian cancer 32 65 (a) PARP1 (VeliBRCA) (a) RECIST or GCIG CA125 criteria.

DNA Cell Survival damage Overall survival benefit in a pre-specified population 2 of smokers in a randomized trial (n = 95)

PARP1 PARP Inhibitor Cancer Cell Death

Pivotal Phase 3 Trials Follow-on Indications Hypothesis Underway

Genetic Defects + 1-3L BRCA Breast Tumors with HRD DNA-Damaging (BROCADE3) Chemotherapy phenotype e.g., Fanconi anemia Inherited defects related, prostate, in BRCA1/2, impair DNA 1L Ovarian pancreas repair (VELIA)

1L NSCLC SQ (VELA) DNA-Damaging Indications where Chemotherapy (non- platinums or topoisomerase BRCA) 1L NSCLC NonSQ inhibitors are used Reliance on (VESTA) as standard PARP-mediated DNA therapies repair (NER/TLS) TNBC Neo-adjuvant (BRIGHTNESS)

« Readouts anticipated between 2017–2019 »

Glioblastoma (GBM) kills more than 95% of those diagnosed • ABT-414 targets unique epitope exposed upon • Most common primary brain tumor in adults EGFR activation (peak age 55–65 yr) • Activation occurs when either EGFR is amplified or • Grows rapidly and infiltrates tissue has vIII mutation • Chemotherapy has marginal benefit • Selective binding to tumors confirmed in first-in- human and imaging studies ̶ Median survival of ~14 months ̶ 5-year survival rate of <5% • No typical EGFR inhibitor skin rash • Worldwide incidence ~28,000

Zirconium ImmunoPET in a patient with GBM ABT-414 ❶ in blood ❷ ABT-414 ❺ binds EGFR Toxin selectively CANCER expressed kills cell CELL on tumor cell ❹ ❸ Toxin releases ABT-414 from ABT-414 enters cell 4h 72h 120h

Best percent change from baseline in tumor size (target lesion) – monotherapy and combination with TMZ in recurrent GBM and EGFR amplified positive –

11 patients had change in tumor sized between 100–850%.

N=99  ABT-414  ABT-414 + temozolomide (TMZ)

As of March 1, 2016.

• Since the first patient with GBM was treated with ABT-414 (2013), ABT-414 has advanced to international, randomized trials • ABT-414 is now being studied in over 30 countries in both recurrent and front-line settings • Collaborations with recognized, academic cooperative groups (EORTC, RTOG) • Biomarker work will refine the population most likely to benefit (e.g., EGFR amp+)

Ph 1 Ph 2 Ph 3 Anticipated Combination Indication (study name) readouts +temozolomide 1L GBM (INTELLANCE-1) 2019 +temozolomide 2L GBM (INTELLANCE-2) 2017 GBM monotherapy GBM (INTELLANCE-Japan) (a) 2018

+temozolomide GBM 2016

(a) Phase I/II.

EORTC – European Organization for Research and Treatment of Cancer. RTOG – Radiation Therapy Oncology Group.

2016 2017 2018 2019 2020

 (RESONATE-2) 1L CLL (approval)  • (Alliance-CTEP) P3, 1L CLL  • (iMMPACT) P2 ibr+vel R/R MM  (HELIOS) r/r CLL/SLL • (PHOENIX) P3, 1L DLBCL * (label expansion, +BR) • (ILLUMINATE) P3, 1L CLL/SLL (+G vs CG) *  Imbruvica • (PCYC1127 ) P3, 1L & r/r WM *  • (PCYC-1129) cGVHD (CLL13) P3, 1L CLL (+GVe) • (DAWN) P2, r/r FL  • (PCYC-1121) P2, MZL • (PCYC-1126e) P3, 1L CLL * • SHINE) P3, 1L MCL * • (PCYC-1137) P2/3, Pancreas * • (SELENE) P3, r/r FL/MZL * • (PCYC-1138) P2, r/r MM *   17p del CLL (approval) • (MURANO) P3, r/r CLL (+R)  • P2, r/r CLL after BRCi  (CLL13) P3, 1L CLL (+GI)  • (CONTRALTO) P2, r/r FL (+R vs BR) (CLL14) P3, CLL (+G) Venclexta • P1, r/r CLL & SLL • (CAVALLI) P2,1L DLBCL (+RCHOP vs RCHOP) (+R, +G, +BR) • P1, r/r NHL (+BR)  • P1, r/r CLL & NHL • P1, r/r MM P3, AML  • P1, r/r MM • P1, AML (+dec, +aza) P3, r/r MM (+bortez/dex) (+bortez/dex) • P1, AML (+Ara-C)

 • (VELA) P3, 1L NSCLC SQ veliparib • (VESTA) P3, 1L NSCLC NSQ  • (BRIGHTNESS) P3, neo-adjuvant TNBC (VELIA) P3, 1L Ovarian • (BROCADE3) P3, 1-3L BRCA Breast  (INTELLANCE-2) P2, 2L GBM  ABT-414  P1, 1L GBM (INTELLANCE-J) P1/2, GBM  (INTELLANCE-1) P3, 1L GBM R=Rituxan; G=Gazyva; BR=bendamustine/Rituxan; CG=chlorambucil/Gazyva; GI=Gazyva/Imbruvica; RCHOP=Rituxan, cyclcophosphamide, doxorubicin, vincristine, prednisone; Bortez=bortezomib; Dex=dexamethasone; Dec=decitabine; Aza=azacitidine; Ara-C=cytarabine. * Interim data

Thomas Hudson, M.D. Background

“In the U.S., one in two men and one in three women will get cancer in their lifetime; one out of four Americans will die from cancer.” - American Cancer Society

In his State of the Union Address, President Obama invited Vice President Joe Biden to champion and spearhead a national effort – a “moonshot” in the fight against cancer.

“I know that we can help solidify a genuine global commitment to end cancer as we know it today — and inspire a new generation of scientists to pursue new discoveries and the bounds of human endeavor.” - U.S. Vice President Joe Biden

Human Genome Project

2003 2007 2013

1990 1995 2000 2004 2005

Thomas Hudson, M.D. Chair, ICGC Executive and International Scientific Steering Committees Cancer Is a Disease of the Genome

Every tumor is different

Every cancer patient is different

• Collect ~500 tumor/normal pairs from each of 50 different major cancer types

• Comprehensive genome analysis of 25,000 cancer genomes, transcriptomes and methylomes

• Make the data available to the research community and public

Identify genome changes

…GATTATTCCAGGTAT… …GATTATTGCAGGTAT… …GATTATTGCAGGTAT…

• The study of cancer genomes offered the potential to identify hundreds of new targets for better diagnoses and drug development

• No cancer genome had been sequenced

• Sequencing 25,000 cancer genomes was deemed an ambitious goal!

• Next generation technologies were on the horizon

• The spectrum of cancers across the world varies greatly

• The founders of ICGC realized the importance of coordination, standardization and need for uniform quality measures to enable the merging of datasets and increasing power to detect new cancer biomarkers and targets

Release 18 55 ICGC projects

14,000 ICGC Data Portal Cumulative Donor Count for Member Projects Release 17 Release 16

12,000 Release 15 Release 14

Release 11 10,000 Release 13

Release 10 Release 12 Number of of Number Donors 8000 Release 9

6000

Release 8 4000

2000

Release 18 55 ICGC projects

14,000 ICGC Data Portal Cumulative Donor Count for Member Projects Release 17 Release 16

12,000 Release 15 Release 14 Cancer pathways Release 11 New biomarkers 10,000 Release 13 New targeted drugs

Release 10 Release 12 Number of of Number Donors New diagnostic tools 8000 Release 9 Precision medicine

6000

Release 8 4000

2000

805 PERSPECTIVES citations

Nature 464, 993-998 (15 April 2010)

Seminal publications reporting new cancer genes and pathways in Nature, Nature Genetics, Science, Cell, etc.

Oncogene inhibition

Pathway inhibition Oncogenes

Cancer genomes as Immuno- DNA damage predictive modulation biomarkers Inhibition of CAR T cells DNA repair DNA Neo- Cancer Instability antigens vaccines

Thomas Hudson, M.D. President and Scientific Director, OICR OICR: An Academic Biotech

The Ontario Institute for Cancer Research (OICR) is a translational research institute headquartered in downtown Toronto’s Discovery District, with an Ontario-wide mandate and global reach

Ontario investments since 2006: $750 M

Other sources (federal, charities, private sector): $540 M

Mission: Partner with the Ontario oncology community to accelerate the development and implementation of clinically important knowledge, products, services and policies to improve cancer prevention, detection, diagnosis and treatment and enable patients in Ontario and worldwide to live longer and better lives.

Translational Research Priorities 1 2 3 THERAPEUTIC CLINICAL POPULATION INNOVATION IMPACT HEALTH

Research areas build on Ontario strengths: Small molecules, biologics, stem cells, imaging, genomics, informatics and bio-computing, pathology, clinical trials and health outcomes.

#1 of 103 for research excellence and impact in Canada

These are size-independent indicators from SCImago institutions rankings 2014

425 1,700 32 colon cancer deaths/year investigators, clinician outstanding scientists/ potentially averted due to scientists, research staff and clinician researchers have been attracted to Ontario improved participation in trainees supported by OICR colon cancer screening research across Ontario

Dr. John Bell OICR Program Director, Immuno- and Bio-therapies (ORBiT) Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute Professor, Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa

Innovative concept of associating tumour vaccine (MAGE-A3) and oncolytic virus (Maraba)

Dr. Brian Lichty • Assay development • Manufacturing • Toxicology (NHP) Phase 1/2 Trial POC • Regulatory (CTA) • Clinical operations 2015-16

2012-2014

Constant interactions between translation teams and basic/science discovery teams Dr. David Stojdl

Build on experience with ICGC, OICR and moonshots • Inspire individuals and groups to think BIG! • Stimulate creative thinking and risk taking • Intensify the interactions between discovery teams and clinician researchers to accelerate translation and make new discoveries • Capitalize on new technologies and new biology

What will be my priorities? • Continue to grow the existing AbbVie Pipeline • Build critical mass in immuno-oncology – Unlock the potential of different types of immune cells – Explore interactions between cancer genome signatures and immune response

Bring long-term benefits to individuals and society

Oncology HCV Neuroscience

Immunology Elagolix Immunology

Shao-Lee Lin, M.D., Ph.D. Development

Lisa Olson, Ph.D. Discovery AbbVie Immunology: A Promise that Extends into the Future

Currently being used to treat more than 975,000 patients in 13 indications worldwide.

20 new molecules PIPELINE being evaluated across 14 disease states.

195 active immunology studies in more than 50 countries.

Rheumatology Dermatology Gastroenterology

Achieve deep response Achieve full clearance Improve remission rates and remission with durable response and achieve mucosal healing Oral agent

Rheumatology Dermatology Gastroenterology

JAK IL-23 IL-23 JAK IL-23 Phase 3 in Phase 2 in Phase 3 in Phase 2 in Phase 2 in RA PsA Psoriasis Crohn’s Crohn’s

ABT-494 has potential Risankizumab has for best efficacy, potential for best ABT-494 and particularly in the most efficacy and most risankizumab both have difficult to treat RA convenient dosing in potential in IBD patients psoriasis

JAK1 inhibition blocks JAK3 inhibition affects cells signaling driving JAK2 inhibition that monitor for tumors rheumatoid arthritis leads to anemia Mechanism of ActionMechanism andof infections Action disease process IL6 IL2 IL-2,4,7,9,15,21 Jak3 inhibition leading to blockade of IL6 Jak3 inhibition leadingEpo to blockade of IL2 Epo IL2 signaling may account for much of IL2 signaling may account for much of CP-690,550’s efficacy Jak1CPJak1-690,550’s efficacy P P P P Erythropoetin promotes erythroid Jak11 ErythropoetinJak13 promotesJak22erythroidJak22 Jak11 Jak33 Jak22 Jak22 P P P P P P P P P differentiation via Jak2 -blockade of P differentiation via Jak2 -blockade of P P P P P which likely accounts for anemia, CP- which likely accounts for anemia, CP- 690,550’s major toxicity 690,550’s major toxicity

However Jak3 participates in multiple Crp However Jak3IFNG participates in multiple IFNG receptor complexes complicating receptor complexesCrp complicating Hb Hb interpretation of interpretation of pharmacodynamic/efficacy pharmacodynamic/efficacy relationships MoleculerelationshipsJAK1 Potency JAK1/JAK2 Selectivity JAK1/JAK3 Selectivity

Although Jak3 deficient humans are ABT-Although494 8.5Jak3 nM deficientIC50 humans74 X are 19 X SCID, pharmacological blockade of SCID, pharmacological blockade of Jak3 is effective against RA apparently Jak3 is effectiveNot for Promotionalagainst Use RA apparentlyR&D Day | June 3, 2016 | Company Confidential © 2016 178 without profound immunosuppression without profound immunosuppression Potential for Best-in-Class Efficacy Among JAK1 Selective Agents

Efficacy of ABT-494 relative to other JAK1 inhibitors based on model-based meta analysis

ACR20 ACR50 ACR70

40 40 40 ABT-494 12 mg BID

ABT-494 6 mg BID

Filgotinib 200 mg/Day 30 30 30 Filgotinib 100 mg QD

Baricitinib 4 mg QD

Baricitinib 2 mg QD 20 20 20

BaricitinibABT-494 Phase2 mg QD 3 Dose Equivalents 10 10 10 15 mg QD = 6 mg BID

30 mg QD = 12 mg BID

0 0 0 Difference from Placebo in Percentage of Subjects Achieving ACR Response *Meta analysis across all clinical trials in RA to date for these agents

ACR20 ACR50 ACR70

40 40 40 ABT-494 12 mg BID (BALANCE I; Phase 2)

ABT-494 12 mg BID (BALANCE I; Phase 2) 30 30 30 Baricitinib 4 mg QD (BEACON; Phase 3)

Baricitinib 2 mg QD 20 20 20 (BEACON; Phase 3)

10 10 10

0 0 0 Placebo-corrected Percent of Responders (Data from cross-study comparison)

MTX-naïve MTX-IR csDMARD-IR MTX-IR Biologic-IR Biologic-IR Type of Mono Combo Combo Mono Combo Combo Therapy Background ̶ MTX csDMARDs ̶ csDMARDs csDMARDs Active MTX Adalimumab Placebo MTX Placebo Abatacept Comparator Duration of 48 weeks 48 weeks 12 weeks 14 weeks 24 weeks 12 weeks Period 1

Supports use earlier Supports use after first in therapy biologic failure

Rapid Phase 2-to-Phase 3 transition for RA. Three months from ‘go’ decision to first subject dosed in Phase 3.

Tofacitinib Filgotinib Baricitinib ABT-494

RA Phase III

PsA Phase IIb/III Rheum

AS Phase II

Atopic Phase II

Dermatitis Derm

CD Phase II

Gastro UC Phase II

= Ongoing program = Planned study

Risankizumab licensed from

risankizumab Risankizumab IL-12 IL-23IL-23 p19 IL-17 IL-22 p35 p40p19 p40 p40 TNFα IL-21 Psoriasis

IL-12Rβ1 IL-23R NFAT Crohn’s disease pSTAT3 IRF4

IL-12Rβ1IL-12Rβ2 IL12Rβ1 P STAT3IL23R P P STAT3 P

TH1 pathway TH17 pathway

Psoriatic arthritis

Risankizumab recognizes an epitope on IL-23p19

• Inhibits binding of IL-23 to its receptor Singh S et al. mAbs 2015;7:778 Patel M et al. Dermatol Ther 2012;2:16 • Binding is highly specific for the p19 subunit Sofen H et al. J Allergy Clin Immunol 2014;133:1032 Mahtur A et al. J Immunol 2007;178:4901 • No direct impact on TH1 pathway Muranski P & Restifo NP. Blood 2013;121:2402

• Expected PASI90 efficacy above anti-IL-12/23, IL-17s and other IL-23s after 12 weeks • Dosing has potential to be the most patient friendly at once every 3 months • Potential for durability above IL-12/23 and IL-17s at one year

Comparison of PASI 90 Scores at 12 wks* Comparison of PASI 100 Scores at 12 wks*

100 100

90 90 Q12W 80 80 Q2W 70 70

60 Q4W 60 Q12W* Q8W Q12W 50 Q2W 50 Q12W Q2W 40 40 Q8W 30 30 Q4W Q12W Q12W* 20 20 Q2W 10 10

0 0

PASI90 and PASI100 data from multiple studies, including: Humira (CHAMPION), Stelara (ave PHOENIX 1+2), Cosentyx (ave ERASURE/ FIXTURE, 300 mg), Ixekizumab (UNCOVER2/3), Tildrakizumab (ClinicalTrials.gov), Guselkumab (NEJM 2015), BI655066 (EADV2015). *Tildrakizumab data at 16wks

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 185 Risankizumab Has Demonstrated Encouraging Phase 2 Data in Crohn’s Disease Clinical Remission (CDAI<150, placebo adjusted, Bio-IR)

Adalimumab week 12 19

Vedolizumab week 10 15 Phase 3 Phase Ustekinumab week 8 14

anti-IL6 Week 12 16

Risankizumab week 12 22

Phase 2 Phase Filgotinib week 10 8

Medi2070 week 8 12

0 5 10 Percent 15 20 25 Data from multiple studies, including: Adalimumab: EXTEND, data on file; Vedolizumab: GEMINI 3; Ustekinumab: UNITI-1; anti-IL6: ANDANTE; Risankizumab: DDW 2016; Filgotinib: ECCO 2016; Medi2010: ECCO 2015 Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 186 Risankizumab Phase 3 Psoriasis Program Includes Two Head-to-Head Studies Versus Stelara

N Trial Name Trial Description Primary Endpoint 500 Phase 3 head-to-head, placebo-controlled study of the efficacy and safety of Risankizumab compared with ustekinumab for moderate-to-severe psoriasis sPGA0/1 @ wk 16 PASI 90 @ wk 16

500 Phase 3 head-to-head, placebo-controlled study of the efficacy and safety of Risankizumab compared with ustekinumab for moderate-to-severe psoriasis sPGA0/1 @ wk 16 PASI 90 @ wk 16

500 Phase 3 placebo-controlled, withdrawal and retreatment study of the efficacy and safety of Risankizumab for moderate-to-severe psoriasis sPGA 0/1 @ wk 16 PASI 90 @ wk 16 600 Phase 3 Risankizumab Compared to Active Comparator (adalimumab) in patients with moderate-to-severe chronic plaque psoriasis sPGA0/1 @ wk 16 PASI 90 @ wk 16

Open-label extension enrolling subjects from all of the Phase 3 Phase 3 LIMMitless efficacy studies completers

Source: www.clinicaltrials.gov

Guselkumab Tildrakizumab LY3074828 MedI2070 Risankizumab

PsA Phase 2 Rheum

Psoriasis Phase 3 Derm

CD Phase 2

Gastro UC Phase 2

= Ongoing program = Planned study

Anticipated News Flow 2Q 2016 3Q 2016 4Q 2016 2017 2018

ABT-494 JAK RA Phase 3 ABT-122 ALX-0061 ABT-981 ABT-981 TNF/IL-17 IL-6 IL-1a/b IL-1a/b RHEUM PsA Phase 2 RA Phase 2 Hand OA Phase 2 Knee OA Phase 2 Risankizumab IL-23 PsA Phase 2

ABT-494 Risankizumab DERM JAK AD Phase 2 IL-23 Pso Phase 3

ABT-494 ABT-494 JAK JAK CD Phase 2 UC Phase 2 ABT-308 ABBV-323

GASTRO IL-13 CD40 EoE Phase 2 Risankizumab Phase 2 Risankizumab IL-23 IL-23 CD Phase 2 UC Phase 2

Rheumatology Dermatology Gastroenterology

JAK IL-23 IL-23 JAK IL-23 Phase 3 in Phase 2 in Phase 3 in Phase 2 in Phase 2 in RA PsA Psoriasis Crohn’s Crohn’s

Our goal is to achieve Developing an oral Unmet need in deep remission. agent with high efficacy. remission and mucosal healing.

Anti-TNF JAK-BTK Anti-TNF Steroid Combo RORgT Steroid ADC ADC

TargetedTargeted Release Release of ofNovel Novel Steroid Steroid Blue = LysoTracker Red = Anti-TNF

Resolution of Disease with a Single Dose Anti-TNF ADC Demonstrates Comparable Efficacy in Mouse Arthritis Model to High Dose Steroid Without Side Effects

1.1

1.0 Single Dose 0.9 Inflammation 0.8 Vehicle 0.7 SM steroid Improvement 0.6

0.5 Anti-TNF mAb 0.4 Bone Pituitary

0.3

0.2

0.1

0.0 Worsening

Change in Paw Swelling (delta mm) Paw in Swelling (delta Change -0.1 Anti-TNF-Steroid ADC 0 7 14 21 28 35 42 49 Days of Disease

Remarkable efficacy with just a single dose of anti-TNF Steroid ADC

Lack of unwanted steroid side effects

Hypothesis: Combining inhibitors of JAK1 and BTK will confer additive efficacy in autoimmune disease

Paw swelling in rat collagen-induced Myeloid arthritis model T-lymphocyte B lymphocyte

+ Combo efficacy

JAK BTK

Fixed Dose JAK BTK JAK Combo BTK Therapy

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 193 Oral Small Molecule for Moderate-to-Severe Psoriasis RORgt Inverse Agonists Target the Clinically Validated IL17/IL23 Pathway

RORgt essential for production of IL-17 Th-17 lymphocyte Differentiation Effector function

RORgt IL-17A

IL-17F Activated TH17 T cell cell RORgt inverse agonist

RORgt inhibition significantly decreased inflammation and 20 ns reduced the frequency of IL17-producing cells **** ****

15 Veh + Veh IL-23 + Veh IL-23 + RORgti

% IL17-producing cells IL17-producing %  99% 0 Veh IL-23 IL-23 + RORgti

Anticipated News Flow 2Q 2016 3Q 2016 4Q 2016 2017 2018

ABT-494 JAK RA Phase 3 ABT-122 ALX-0061 ABT-981 ABT-981 ABBV-599 Anti-TNF-Steroid TNF/IL-17 IL-6 IL-1a/b IL-1a/b JAK-BTK Phase 1 ADC Phase I RHEUM PsA Phase 2 RA Phase 2 Hand OA Phase 2 Knee OA Phase 2 Risankizumab IL-23 PsA Phase 2

ABT-494 JAK AD Phase 2 Risankizumab DERM IL-23 ABBV-553 Pso Phase 3 RORgT Phase 1

ABT-494 ABT-494 JAK JAK CD Phase 2 UC Phase 2 ABT-308 ABBV-323

GASTRO IL-13 CD40 EoE Phase 2 Risankizumab Phase 2 Risankizumab IL-23 IL-23 CD Phase 2 UC Phase 2

Shao-Lee Lin, M.D., Ph.D. HCV

Oncology HCV Neuroscience

Immunology Elagolix Advancing the Next Generation of HCV Cure

Current therapies Unmet Need: AbbVie’s Next Gen: • >1 million • >100 million patients remain* patients cured Once-daily oral combo • Cure rates >95% • Pan-genotypic • Resistance associated variants ABT-530 for many NS5A inhibitor genotypes • Difficult to treat populations • Shorter treatment durations + ABT-493 NS3/4a protease inhibitor

* WHO assessment (many are undiagnosed)

ABT-530

NA NA

NA: Data not available Source: AbbVie data on file

ABT-493 300mg + ABT-493 300mg + ABT-530 120mg + ABT-530 120mg Ribavirin 800mg

SVR12, n (%) 90.1 (20/22) 86.3% (19/22) Breakthrough 0 1 Relapse 1 0 Other 1* 2**

mITT SVR12, n (%) 95.2% (20/21) 95% (19/20)

* 1 LTFU, ** 1 death from CA after UD RNA at PTW 8 and 1LTFU

Baseline Resistance-Associated Variants 82% patients with RAVs at NS3 and/or NS5A 32% with both NS3 and NS5A RAVs detected 24% with double- or triple-NS5A RAVs

Duration SVR (non-virologic failures

GT/ F stage Treatment History 12 1

- (weeks) excluded) Treatment naïve and experienced 8 100% Treatment naïve and

1/ F0-F3 experienced 12 100% 1 and MAGELLAN and 1 - First-generation DAA experienced 12 95% treatment failures Treatment naïve and

1/ F4 experienced 12 96%

SUREVEYOR 2 - Treatment naïve and experienced 12 100% 2/ F0-F3 Treatment naïve and

experienced 8 100% SUREVEYOR

Treatment naïve and a

experienced 12 97%

2 - 3/ F0-F3 Treatment naïve 8 100% GT3 non-cirrhotic

Experienced 12 92% SUREVEYOR GT3 compensated Treatment naïve 12 b

1 3/ F4 100% - cirrhotic

Treatment naïve and

4-6/ F0-F3 experienced 12 100% SUREVEYOR a. SVR12 in TN patients was 100%; b. Screening of GT3 cirrhotic PR-exp. was stopped prematurely (FDA recommendation); only 4 GT3 cirrhotic PR- experienced (not included in the table) were randomized and their duration was extended to 16 weeks, 1 out of these 4 patients relapse. DAA = Direct Acting Antivirals

Duration SVR (non-virologic failures

GT/ F stage Treatment History 12 1

- (weeks) excluded) Treatment naïve and experienced 8 100% Treatment naïve and

1/ F0-F3 experienced 12 100%

1 and MAGELLAN and 1 - DAA experienced 12 95% Treatment naïve and

1/ F4 experienced 12 96%

SUREVEYOR 2 - Treatment naïve and experienced 12 100% 2/ F0-F3 Treatment naïve and

experienced 8 100% SUREVEYOR

Treatment naïve and a

experienced 12 97%

2 - 3/ F0-F3 Treatment naïve 8 100%

Experienced 12 92% SUREVEYOR Treatment naïve 12 b

1 3/ F4 100% -

Treatment naïve and 8wk regimen being 4-6/ F0-F3 12 100%

experienced tested in Phase 3 SUREVEYOR a. SVR12 in TN patients was 100%; b. Screening of GT3 cirrhotic PR-exp. was stopped prematurely (FDA recommendation); only 4 GT3 cirrhotic PR- experienced (not included in the table) were randomized and their duration was extended to 16 weeks, 1 out of these 4 patients relapse. DAA = Direct Acting Antivirals

ENDURANCE MAGELLAN EXPEDITION SURVEYOR

DAA naïve Special populations Non-cirrhotic DAA experienced Difficult to treat GT1, GT2, GT4-6 Pan-genotypic Cirrhotic and GT3 cirrhotic Cirrhotic HIV co-infection Non-cirrhotic 8wks in GT2, GT4-6 Renal impairment Tx as short as 8wks

Next Gen commercialization expected in 2017

Oncology HCV Neuroscience

Immunology Elagolix Elagolix Profile

Attributes and Mechanism of Action Female HPG Axis • Orally active • Gonadotropin releasing hormone (GnRH) antagonist • Dose dependent suppression of estrogen and progesterone • Rapid onset of action and readily reversible when therapy stopped • Potential for management of hormonally-mediated conditions, such as endometriosis and uterine fibroids

Endometriosis Abnormal growth of endometrial tissue • Tissue that lines the uterus grows outside of the uterus • Tissue is responsive to estrogen

Epidemiology • Endometriosis affects an estimated 176 million women worldwide.1

Symptoms: • Menstrual pain (Dysmenorrhea) • Chronic non-menstrual pelvic pain • Infertility

1 The World Endometriosis Research Foundation: Facts about Endometriosis.

Laparoscopic Surgery GnRH agonists

High • Invasive • Complete hormonal • High recurrence suppression • Adhesions ELAGOLIX

Efficacy EAP on Efficacy Analgesics OCPs: low efficacy Depo-Provera: Low side effects

Less “Invasiveness” More

Unmet • Oral agent • Laparoscopy not required to • Rapid reversibility initiate treatment Need • Significant pain reduction • Long-term efficacy

Violet Petal Solstice Responder Rates Responder Rates * * * * 76.9 80 75.8 75.3 80 72.4 70 70 60 60 * 46.4* * * 46.2 50 42.1 50 43.4 40 40 30 30 22.7 25.4 19.6 23.1 20 20 10 10 0 0 Month 3 Month 6 Month 3 Month 6 PBO (n=373) PBO (n=353) E150 QD (n=248) E150 QD (n=221) E200 BID (n=244) E200 BID (n=225) PBO (n=372) PBO (n=355) E150 QD (n=247) E150 QD (n=221) E200 BID (n=243) *P vs. PBO: <0.001 E200 BID (n=225) *P vs. PBO: <0.001

Violet Petal Solstice Responder Rates Responder Rates * * 70 62.1 70 * 62.2 * 57.8 60 * 54.5 60 *** ** 50.4 ** 49.8 51.6 50 45.7 50 40.6 40 36.5 34.9 40 36.5 30 30 20 20 10 10 0 0 Month 3 Month 6 Month 3 Month 6 PBO (n=373) PBO (n=353) E150 QD (n=248) E150 QD (n=221) E200 BID (n=244) E200 BID (n=225) PBO (n=372) PBO (n=355) *P vs. PBO: <0.001; *P vs. PBO: <0.001; E150 QD (n=247) **P vs. PBO: <0.01; E150 QD (n=221) **P vs. PBO: <0.01; E200 BID (n=243) ***P vs. PBO: 0.003 E200 BID (n=225) ***P vs. PBO: 0.003

Violet Petal Solstice Lupron 1 1 1 0.53 0.49 0.5 0.5 0.5 0 0 0

-0.5 -0.32 -0.5 -0.5 -0.3 -1 ** -1 -0.71 -1 -1.5 -1.5 * -1.5 -2 -2 -2 -2.5 -2.5 -2.5 -2.45 -3 -2.64 -3 -3 * -3.5 * -3.5 -3.5 -3.2 * PBO PBO Lupron

E150 QD E150 QD Lupron + add-back

E200 BID E200 BID

• Limited BMD decrease at Elagolix 150 mg QD Lupron approved • Higher BMD decrease at 200 mg BID for 6mo use – Options for bone protection are under evaluation, including hormonal add-back therapy *P vs. PBO: <0.001 • Lupron 3.75 mg IM dosed monthly, is approved for 6 months when **P vs. PBO: 0.002

used without hormonal add-back therapy BMD measured in Lumbar Spine

Uterine Fibroids Benign uterine tumors • One or multiple tumors • Tumors are estrogen and progesterone responsive • Resolve after menopause

Epidemiology • Estimated that the lifetime incidence in pre-menopausal women is 50–80%

Symptoms: • Heavy menstrual bleeding, often with anemia • Bulk symptoms (e.g., pelvic pressure, urinary frequency, etc.) • Early pregnancy loss and infertility

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 211 Elagolix Has the Potential to Provide a Continuously Effective Treatment for Heavy Menstrual Bleeding (HMB) Associated with Uterine Fibroids (UF)

Hysterectomy GnRH agonists • Fertility loss

High • Surgical risk • Pre-op short term use • No approved add-back Myomectomy

ELAGOLIX • High recurrence Efficacy HMB on Efficacy OCPs, Progestins • Short-term use

Low • Limited Efficacy

Less “Invasiveness” More

Unmet • Long-term efficacy without surgery Need

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 212 Elagolix Demonstrated Marked Efficacy in Uterine Fibroids in Ph2b Add-back Therapy Is Effective in Preventing Loss of Bone Density

Heavy Menstrual Bleeding Bone Mineral Density

* 100 91.9 1 0.78 85.5 90 0.5 * 79 80 0 70 -0.12 -0.5 60 ** 50 -1

40(HMB) Responders -1.5 26.6 30 -2 20 -2.5 10 of Percent -3 0

PBO (n=64) E300 BID E300 BID + E300 BID + BMD Spinal in Baseline from Change -3.5 (n=62) LDA (n=62) add-back -3.59 (n=62) -4 * Placebo E Alone E + add-back

E = Elagolix 300 mg BID *P vs. PBO: <0.001; Add-back = standard dose Activella (E2 1.0 mg/ NETA 0.5 mg) QD **P vs. PBO: 0.148

2010 2014 2015 2016 2017 2018 2019 2020

Violet Petal Violet Petal 6mo data 12mo data Final data

Solstice Solstice 6mo data 12mo data

Regulatory Regulatory ENDOMETRIOSIS Elagolix submission approval licensed from Neurocrine Biosciences Phase 3 #1 12mo Final 6mo data data data

Phase 3 #2 Regulatory Regulatory

6mo data submission approval UTERINE UTERINE FIBROIDS

Oncology HCV Neuroscience

Immunology Elagolix Zinbryta and ABT-555

Laura Gault, M.D., Ph.D. Development Eric Karran, Ph.D. Discovery AbbVie Neuroscience: Providing Novel and Effective Treatments for Neurodegenerative Disorders

Parkinson’s Disease Multiple Sclerosis Alzheimer’s Disease Symptomatic Treatments Immunomodulation, Disease Modification Disease Modification Neuroprotection, Neuroregeneration

• Less invasive, efficacious • Higher efficacy and • Maintain function symptomatic treatments manageable safety • Identify appropriate • Halt disease progression • Improve function time to initiate treatment

Parkinson’s Disease Multiple Sclerosis Alzheimer’s Disease

Duodopa/Duopa: Zinbryta: ABBV-8E12: Levodopa-Carbidopa Anti-CD25 mAb Anti-tau mAb Intestinal Gel • Partnered with Biogen • Phase 1 • Marketed worldwide • Demonstrated reduction in • Targets tau pathology • Improves function relapse and disability progression • Initial antibody development in Holtzman lab at Washington ABT-555: RGMa mAb University • Phase 1 • Extensive preclinical evidence of neuroprotection and regeneration • Based on biology pioneered at AbbVie*

* Demicheva et al., 2015, Cell Reports 10:1-12

MS progression over time 1. Inflammation 2. Demyelination 3. Axonal loss 4. Atrophy

Time since onset of disease

Inflammation in the CNS

Regeneration Neurodegeneration

MS = Multiple Sclerosis CNS = Central Nervous System

Inflammation Demyelination Neuronal Loss

Platform agents such as interferons Drugs that promote remyelination or reduce the number of inflammatory neuronal regeneration will be an important relapses component of the future treatment paradigm

AbbVie is committed to meeting all the needs of patients with MS: • Zinbryta will provide a novel immunomodulatory treatment option for patients • ABT-555 under evaluation for neuroprotective and neuroregenerative effects

• Age of onset in the 30s, with unpredictable severity and progression

• Relapses often occur on initial therapies, prompting switch to another medication

• Drug efficacy/safety profiles inform the right choice for each patient

• New treatments with novel mechanisms of action are needed to provide additional individualized treatment options

ZINBRYTA • Humanized IgG1 mAb that binds specifically to the α-subunit of the IL-2 CD25 interleukin-2 receptor (CD25, α IL-2Rα) • Novel biology – selectively blocks β γ high affinity IL-2 receptor signaling: CD122 CD132 – Specifically inhibits activated effector T cells – Expands immunoregulatory IL-2R CD56brightNK cells – Decreases regulatory T (Treg) cells – Immunomodulatory effects without broad immune cell depletion

Bielekova B, et al. Proc Natl Acad Sci U S A. 2006;103:5941-5946. Bielekova B. Neurotherapeutics. 2013;10:55-67.

SELECT STUDY DECIDE STUDY

0.50 0.46 0.50

54% 50% 0.395 0.40 0.40 45% reduction reduction, reduction, P<0.0001* P=0.0002* p<0.0001 0.30 0.30 0.23 0.21 0.216 0.20 0.20

0.10 0.10

Annualized relapse rate Annualized relapse rate

0.00 0.00 Placebo Zinbryta Zinbryta IFN Beta-1a Zinbryta (n=196) 150mg 300mg (n=922) 150mg (n=201) (n=203) (n=919)

Zinbryta 150 mg demonstrated a 54% reduction in Zinbryta 150 mg demonstrated a 45% reduction in annualized relapse rate v placebo over 52 weeks annualized relapse rate v IFN beta-1a at 2-3 years

12 week confirmed disability progression 12 week confirmed disability progression

13% (placebo) v 6% (Zinbryta), p = 0.02 14% (IFN beta-1a) v 12% (Zinbryta), p = 0.16

Gold et al., Lancet 2013 (SELECT); Kappos et al., NEJM, 2015 (DECIDE)

• Overall exposure in clinical trials is approximately 4,100 patient years – 2,133 MS patients treated with Zinbryta, for up to six years

• Warnings include: Hepatic injury, immune mediated disorders, acute hypersensitivity, infections, depression and suicide

• The most common adverse reactions (incidence ≥5% and ≥2% higher incidence than comparator) were: Nasopharyngitis, upper respiratory tract infection, influenza, dermatitis/rash, oropharyngeal pain, bronchitis, eczema, lymphadenopathy, depression, pharyngitis, and increased alanine aminotransferase (ALT)

• Zinbryta risks and side effects are generally manageable, including a REMS program with monthly monitoring

Increased efficacy (v IFN beta-1a) with a unique mechanism of action and convenient administration

• Novel mechanism of action that inhibits activated T-cells, while major immune cell subsets (T, B, NK) remained within normal ranges • Zinbryta has shown superior, sustained efficacy versus IFN beta-1a (a standard first line therapy) • Zinbryta risks and side effects are generally manageable, including a REMS program with monthly monitoring • Monthly, self-administered subcutaneous dosing

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 225 A Fundamental Abnormality in MS and Spinal Cord Injury is Increased RGMa; Neutralizing RGMa Is a Way to Allow Nerves to Regenerate

ABT-555 ABT-555 ActivatedRGMa MicrogliaRGMa T-Cell Macrophage

RGMa expression in MS promotes degeneration ABT-555 blocks the effects of RGMa enabling and inhibits axon regrowth and remyelination axonal regeneration and remyelination

Not for Promotional Use R&D Day | June 3, 2016 | Company Confidential © 2016 226 Anti-RGMa mAbs Demonstrated Neuroprotective and Neuroregenerative Effects in Preclinical Models of Neuroinflammatory Injury

Targeted Optic Nerve Model Targeted Spinal EAE Model

Control Ab Anti-RGMA Ab Treatment

• Inflammatory cytokines injected into • Injection of inflammatory cytokines into rat optic nerve spinal cord • Rats treated systemically with anti-RGMa • Anti-RGMa antibody administered after injury at antibody showed increased growth of weekly intervals improved recovery nerve fibers into inflammatory lesion

Control Ab Anti-RGMa Ab Normal retina Injury Model

• Preclinical experiment in rats that recapitulates aspects of optic neuritis

• Treatment with anti-RGMa antibody preserved approximately 80% of axons compared to only 10% in control antibody treatment group

• Anti-RGMa antibody treatment prevents degeneration of the retinal fiber layer measured by optical coherence tomography (OCT)

First patient dosed Initial evidence of biologic activity Multiple Sclerosis

2016 2017 2018

Spinal Cord Injury Patient first dosed Initial evidence of biologic activity

• 115 million AD patients by 2050 • Cost of care in the US was $225 billion in 2015; will be $1.1 trillion by 2050 • Therapeutic options for AD are limited; progress lags well behind successes in oncology, inflammation, metabolic diseases and cardiology

15-20 years

Plaques Tau Aβ peptide Tangles

 Amyloid plaques - do not correlate with death of neurons or clinical symptoms

 Tau tangles - do correlate with death of neurons and clinical symptoms

15-20 years

Biochemical phase Cellular phase Clinical phase

2010 2016

Karch and Goate Biol.Psych 77:43-51 (2015)

2010 2016

Growing understanding of the underlying pathobiology Primarily Aβ Increased approaches target diversity

http://memory.ucsf.edu/research/studies/eoad

2010 2016

Growing understanding of the underlying pathobiology Primarily Aβ Increased approaches target diversity

Availability of biomarkers Trials frequently omit Amyloid imaging broadly biomarkers of target available, tau imaging engagement & efficacy emerging, CSF biomarkers

Liu-Siefert et al Alz Dem Trans Cli In 1:111-121 (2015)

2010 2016

Growing understanding of the underlying pathobiology Primarily Aβ Increased approaches target diversity

Availability of biomarkers Trials frequently omit Amyloid imaging broadly biomarkers of target available, tau imaging engagement & efficacy emerging, CSF biomarkers

Novel clinical trial designs Mild to moderate patients MCI/presymptomatic patients

• To gain a fundamental understanding of disease processes and targets. • To execute the highest caliber science internally and with world-class academic researchers and biotechs. • To populate the AbbVie Neuroscience portfolio with innovative drug targets. • Three focus areas: – Tau pathobiology spreading through the brain – Neuroinflammation: Microglial biology informed by new genetic findings – Autophagy: Why can’t brain cells clear abnormal, toxic protein aggregates?

Rare causal mutations

Dementia C < A

Familial Sporadic D = B AD AD All causal mutations increase the probability of amyloid depositing in the brain. This is consistent with amyloid triggering the D B disease process, rather than driving it. Normal Karran et al Nat Rev Drug Dis 10:698-712 (2011)

20 C 40 Age/Years 60 A 80 Age of Age of Death Death onset onset

Ab Tau pathology Phase III pathology trials

Sporadic AD – Familial AD onset AD delayed

Causal mutation

Ab therapeutic

0 40 60 80 100 120 Age/Years Clinical Clinical Clinical symptoms symptoms symptoms Karran et al Nat Rev Drug Dis 10:698-712 (2011)

Normal

Alzheimer’s Disease

Brunden et al Nat Rev Drug Disc 8:783-793 (2009)

Normal

Alzheimer’s Disease

Brunden et al Nat Rev Drug Disc 8:783-793 (2009)

• Tau pathology correlates spatially with symptomatology • Amyloid does not

Ossenkoppele et al Brain 139: 1551-1567 (2016)

Braak stages I-II III-IV V-VI

Braak & Braak Acta Neu 82:239-259 (1991)

Therapeutic intervention

Wischik et al Em Drugs & Targets For AD 1:210-232 (2010)

Misfolded Seeds Anti-tau antibody

Monomers

Process 2 repeated. Tau 3 1 pathology is ABBV 8E12 antibody spread along prevents misfolded Misfolded tau “seeds” neuronal seeds from being released into pathways and taken up by synapses and taken networks downstream neurons up by 2⁰ neurons. – pathology is Serve as templates ameliorated that seed further aggregation in downstream neuron

In-licensed from C2N in March 2015

Anti-tau antibody inhibits tau seeding in vitro Anti-tau antibody reduces tau aggregates in vivo (P301S) tau transgenic mouse

Yanamandra et al Neuron 80:402-414 (2013)

First Initial evidence patient dosed of biologic activity Alzheimer’s Disease 2015 2016 2017 2018

Progressive Supranuclear Palsy First patient dosed Initial evidence Additional evidence First opportunity to of biologic activity of biologic activity demonstrate clinical efficacy

• The inauguration of the Foundational Neuroscience Center in Cambridge exemplifies AbbVie’s commitment to finding effective disease-modifying therapies for Alzheimer’s disease. • The FNC will grow over the next two years and deliver new therapeutic targets to the neuroscience portfolio. • Neuroscience is developing a suite of anti-tau antibodies to augment our first clinical candidate ABBV 8E12.