Abbvie R&D Deep Dive

AbbVie R&D Deep Dive

March 10, 2020 Forward-Looking Statements and Non-GAAP Financial Information

Some statements in this presentation are, or may be considered, 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 2019 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 available in the appendix to this presentation and on the company’s website at www.abbvieinvestor.com. Evolution of AbbVie R&D Evolution of AbbVie R&D

Mike Severino, M.D., Vice Chairman and President

We have built an innovation-driven R&D organization with outstanding execution and a consistent stream of new medicines that elevate the standard of care and address significant unmet need

Annual R&D Investment (adjusted) 14 Major Approvals Since 2013 Therapeutic Focus Areas $5B +76% Immunology 4 Growth Oncology 6 $2.8B Neuroscience 1 Virology 2 Women's Health 1 2013 2019

Totaled ~$9 billion in 2019

Recently Launched Medicines Current Approved Indications

Psoriasis

Rheumatoid arthritis

CLL and transplant ineligible AML

CLL, MCL, MZL, cGVHD

HCV

Endometriosis

Current Approved Indications Future Disease Areas

• Psoriasis • Psoriatic arthritis • Crohn’s disease • Ulcerative colitis

• Rheumatoid arthritis • Atopic dermatitis • Crohn’s disease • Psoriatic arthritis • Ulcerative colitis • Ankylosing spondylitis • Giant cell arteritis • Non-radiographic Axial SpA

• CLL and transplant • AML (1L fit, r/r) • MCL ineligible AML • MM t(11;14) • MDS

• Endometriosis • Uterine fibroids

New Indications Represent ~$3.2Bn in 2020 Significant Growth Opportunity

Existing Therapies Expanding Anticipated POC Readouts Launching New Assets into Important New Areas from Early-Stage Pipeline

Navitoclax • ABBV-3373 (TNF/steroid ADC) RA Ph2 PsA AD • ABBV-599 (JAK/BTK) RA Ph2 CD HS • Current therapies provide symptom relief, with • Ravagalimab (ABBV-323; CD40) UC Ph2 UC minimal impact on underlying course of the disease • ABBV-157 (RORgt) Ps Ph1 • Teliso-V (cMet ADC) Solid Tumor Ph2

• Compelling POC data illustrate opportunity • ABBV-155 (BCL-xLi ADC) Solid Tumor Ph1 2020 to transform the treatment of myelofibrosis • ABBV-927 (CD40 agonist) Ph1 AD CD • Elezanumab (RGMa) MS Ph2 PsA UC • Potential for accelerated approval in 2022 • ABBV-8E12 (Tau) AD Ph2 AS GCA • VENCLEXTA Solid Tumor Ph1 AxSpA • ABBV-368 (OX40) Ph1 ABBV-951 • ABBV-621 (TRAIL) Ph1 • Innovative, subcutaneous delivery system • ABBV-647 (PTK7 ADC) Ph1 • ABBV-011 (SEZ6 ADC) Ph1 for L-dopa / C-dopa prodrug AML MCL • TNB-383B (CD3-BCMA) Ph1 • Represents a transformational improvement • ABBV-321 (EGFR ADC) Ph1 MM MDS • TTX-030 (CD39) Ph1

Solid Tumors to current treatments for advanced PD • ABBV-151 (GARP+TGF-β1) Ph1 2021 • Potential to significantly broaden addressable patient • ABBV-CX-2029 (CD71) Ph1 • ABBV-599 (JAK/BTK) SLE Ph2 population beyond those treated with DUOPA today • ABBV-2222/ABBV-3067 CF Ph2 1L MCL • Elagolix (GnRH) PCOS Ph2 1L cGvHD • ABBV-467 (MCL-1) Ph1 Veliparib • ABBV-744 (BET) Ph1 FL • Developed to combine with chemo earlier • ABBV-184 (Survivin-CD3) Ph1 • Scripps (DUPA-CD3) Ph1 in treatment paradigm, as well as to expand into • Harpoon (Survivin-CD3) Ph1 non-BRCA deficient tumors • Harpoon (BCMA-CD3) • Calibr (CD19 sCAR-T) Ph1

UF 2022 • BRCA breast and 1L ovarian cancers represent • AL002 (TREM2) AD Ph1 PCOS a several hundred-million-dollar opportunity for • AL003 (CD33) AD Ph1 our oncology franchise

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 7 Our early-stage pipeline will drive additional growth in oncology ONCOLOGY Late-Stage Pipeline First and best-in-class assets in apoptosis that will expand into solid tumors Navitoclax Veliparib Myelofibrosis BRCA Breast Ovarian • Navitoclax, a BCL-XL inhibitor, moving to pivotal studies

• BCL-XL inhibition in solid tumors require higher levels; addressed using ADC modality

• TRAIL and MCL-1 are expressed in solid and heme malignancies Select Early- to Mid-Stage Pipeline

Immuno-oncology ABBV-151 (GARP+TGF-β1) ABBV-744 (BET) TNB-383B* (CD3-BCMA) • Novel assets that restore T-cell killing activity in ABBV-155 (B7H3 BCL-XLi ADC) ABBV-927 (CD40) TTX-030* (CD39) the tumor microenvironment (i.e., GARP, CD39) ABBV-321 (AM1 PBD) ABBV-CX-2029 (CD71) Teliso-V (cMet) ABBV-368 (OX40) ABBV-647 (PTK7) • Superior CD3 bispecific for both heme and ABBV-621 (TRAIL) ABBV-011 (SEZ6) solid tumors

*Partnered assets AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 8 Our leadership in immunology will drive significant indication expansion for existing therapies IMMUNOLOGY Select Early- to Mid-Stage Pipeline SKYRIZI and RINVOQ • ABBV-3373 is a TNF steroid ADC. We believe this technology • Meaningful improvements over the standard of care can serve as a platform to take us into a broad set of diseases, including rheumatoid arthritis, lupus and multiple other TNF- • Indication expansion/adjacencies mediated diseases Next-generation assets: • ABBV-599 is a BTK JAK1 combination being • Novel platforms: Steroid ADCs to drive deeper studied for rheumatoid arthritis and lupus responses without steroid adverse effects • Ravagalimab is a CD40 antagonist being • New mechanisms (i.e., barrier function in IBD) studied in inflammatory bowel disease • Combinations for indications where many pathways are implicated (i.e., lupus) • ABBV-157 is a small molecule (RORγt) in development for psoriasis

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 9 Our neuroscience research focuses on identification of novel disease modifying therapies NEUROSCIENCE Late-Stage Pipeline • ABBV-951 is a non-surgical option to deliver levodopa/carbidopa, • Near-term assets such as ABBV-951 for offering predictable symptom control without the need for surgery. Parkinson’s disease (PD) ABBV-951 is being investigated for the treatment of PD

• Neural protection for MS, SCI and stroke • Discovery focused on disease-modifying Early- to Mid-Stage Pipeline treatments for Alzheimer’s disease (AD) and PD • Elezanumab: mAB RGMa inhibitor being investigated to treat spinal cord injuries and • Beyond the beta amyloid hypothesis multiple sclerosis • Misfolded proteins, such as tau and α-synuclein • Tau: We are pursuing multiple approaches to modify pathogenic tau, including mAB (8E12) in Phase 2, vectorized delivery of mAB and gene knockdown • Genetically validated mechanisms such as neuroinflammation • TREM2 and SIGLEC3/CD33: Genetically validated targets being studied for their potential as disease modifying agents in AD o AL003*: mAB that works by blocking the function of SIGLEC3/CD33 to increase the activity of microglia and treat AD o AL002*: mAB that enhances the activity of TREM2 and is being developed for the treatment of AD • ABBV-0805: A humanized mAB targeting α-synuclein being investigated for the treatment of PD

Retained core capabilities and built additional Decreased the lead optimization time to key competencies in computational biology, first in human cycle time in our discovery immuno-oncology, genetics and genomics and portfolio by approximately 6 months clinical trial simulation 6

Investigated nearly 300 new targets from Expanded our presence in biotech 2014 to 2018 (approximately 60 per year) hubs on the East and West Coasts

Introduced important new modalities in our discovery portfolio, including 60% of our global R&D organization small interfering RNA (siRNA), cell- is new to AbbVie since 2013 based therapies, next-generation iADCs, CD3 bispecifics and gene delivery

North Chicago, IL Ludwigshafen, Germany

East Coast, MA West Coast, CA Tokyo, Japan

Our capabilities will help drive the next phase of our strategy focused on pipeline advancement and driving industry-leading performance

Bioinformatics Genetics and Molecular Modeling Genomics and Medicinal Chemistry

Protein Precision Innovation in Engineering Medicine Clinical Trials

Our support for basic scientific research is attracting leading scientific talent

Thomas Hudson M.D. Jose-Carlos Gutierrez-Ramos, Ph.D. Neil Gallagher, M.D., Ph.D. Senior Vice President, R&D Vice President, Discovery Vice President, Development Chief Scientific Officer Chief Medical Officer

• Led team at MIT that mapped the human genome, • Immunochemist with strong academic track record and • Gynecological oncologist with more than an early milestone of the Human Genome Project diverse senior R&D leadership roles across a range of 15 years of leadership experience at peer biopharma • Foundational work in understanding human genetic biotech start-ups and peer biopharma companies companies developing oncology drugs across all diversity that led to the haplotype map project and • Deep expertise in translating new areas of science into phases of development, including cytotoxics, small genome-wide association study (GWAS) methods to successful drug discovery programs, from inflammasome molecule kinase inhibitors and biologics discover genes involved in common diseases such as and epigenetics to decoding the human immune to enable • Deep expertise in developing oncology drugs in asthma, diabetes, Crohn’s disease and colon cancer a new generation of curative immune medicines hematological malignancies, such as AML and CML • Founder of the International Cancer Genome Consortium, • Founding CEO of two biotech companies (Synlogic, Cogen) • Oversaw the Novartis Oncology development portfolio, a global effort to discover new cancer genes for focused on transformational science, led from academic including Tasigna, Glivec, ABL001, Arzeera and diagnostics and drug development science to clinical stage programs, raised capital and took Odomzo the companies in the public market or M&A, respectively • Foundational work in the role of CD40 signaling in • Teams under his direction discovered and developed cancer cells and the potential therapeutic use of a marketed products Entyvio/Vedolixumab and trimerized CD40 ligand Xeljanz/Tofacitinb; in addition, teams under his management across three companies have produced four Phase III assets and 11 Phase II programs

Heather Maecker, Ph.D. Timothy Radstake, M.D., Ph.D. Eric Karran, Ph.D. Director, Immuno-Oncology Discovery Senior Medical Director Vice President, Discovery Neuroscience Research Genentech, Stanford University UMC Utrecht, Radboud University Alzheimer’s Research UK, Johnson & Johnson

Mohamed Zaki, M.D., Ph.D. Lisa Olson, Ph.D. Tammy Dellovade, Ph.D. Vice President, Global Head Vice President, Discovery, Director, Research Fellow, of Hematology Development Site Head, East Coast In Vivo Pharmacology Celgene, Sanofi University of Illinois at Urbana-Champaign, Merck, University of Virginia University of Chicago Mirella Lazarov, DDS, Ph.D. Head, Companion Diagnostics Center of Excellence Gilead, Stanford University

Genetics & Howard Jacob, Ph.D. Genomics Vice President, Head of Computational Biology Group and the Genomics Research Center Harvard Medical School, Medical College of Wisconsin, The Whitehead Institute

Kyle Holen, M.D. Innovation in Head, Development Design Center Columbia University College of Physicians and Surgeons, Memorial Sloan-Kettering Cancer Clinical Trials Center

Ian McCaffery, Ph.D. Precision Vice President, Precision Medicine Medicine Janssen, Genentech, University of Leeds AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 15 AbbVie R&D Pipeline - 2013 As of January 15, 2013 Select Pipeline Assets and Programs

Phase 1 Phase 2 Registrational / Phase 3 Submitted

■ ABT-493/ABT-530 (NS3/4A / NS5A): HCV ■ BT-061 (CD4): RA ■ VIEKIRA PAK: HCV ■ DUOPA (dopamine receptor): PD (US) ■ ABT-122 (TNF/IL-17): RA ■ BT-061 (CD4): Ps ■ HUMIRA (TNF): HS ■ VENCLEXTA (BCL-2): Lupus ■ GLPG0634 (JAK1)*: RA ■ HUMIRA (TNF): SpA peripheral ■ RINVOQ (JAK1): RA ■ ABT-126 (a7 NNR): AD ■ HUMIRA (TNF): Uveitis ■ ABT-981 (IL-1 a/b): Osteoarthritis ■ ABT-126 (a7 NNR): Schizophrenia ■ Daclizumab (CD25): MS ■ ABT-354 (5-HTG): AD ■ ABT-436 (V1b): MDD ■ ORILISSA* (GnRH): Endometriosis ■ ABT-419 (GlyT1): Schizophrenia ■ ABT-110 (NGF)*: Pain ■ ABT-957 (Calpain): AD ■ Veliparib (PARP): BRCA Breast Cancer ■ VENCLEXTA* (BCL-2): CLL ■ Veliparib (PARP): Lung Cancer ■ ABT-348 (Aurora): Solid/Heme Tumors ■ Veliparib (PARP): Brain Metastasis ■ ABT-414 (EGFR)*: GBM ■ ABT-719 (MCR)*: Acute Kidney Injury ■ ABT-700 (cMet)*: Solid Tumor ■ Atrasentan (ETA): Diabetic Kidney Disease ■ ABT-767 (PARP): Solid Tumor ■ ORILISSA (GnRH): Uterine Fibroids

Oncology

Immunology

Neuroscience

Other

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 16 *Partnered Asset; Partnership Summary Below: Venclexta – Developed by AbbVie and Roche, commercialized by AbbVie and Genentech, a member of the Roche Group; ABT-414 – Developed by AbbVie researchers with components in-licensed from Life Sciences Pharmaceuticals and Seattle Genetics; ABT-700 – Licensed from Pierre Fabre SA, development and commercialization led by AbbVie; GLPG0634 – Discovered, developed and commercialized in a global alliance with Galapagos NV; ABT-110 – Developed in partnership with PanGenetics; ABT-719 – Developed in partnership with Action Pharma and Zealand Pharma; Viekira Pak and Mavyret – In partnership with Enanta; Daclizumab – Developed in partnership with Biogen; Elagolix – Developed in cooperation with Neurocrine Biosciences AbbVie R&D Pipeline - 2020 As of February 7, 2020 Select Pipeline Assets and Programs

Phase 1 Phase 2 Registrational / Phase 3 Submitted

■ ABBV-157 (RORgT) ■ SKYRIZI* (IL-23): Atopic Derm ■ RINVOQ (JAK 1): PsA ■ ORILISSA* (GnRH): Uterine Fibroids (US) ■ ABBV-154 (TNF-Steroid ADC) ■ SKYRIZI* (IL-23): HS ■ RINVOQ (JAK 1): CD ■ ABBV-151 (GARP+TGFb1): Solid Tumor ■ ABBV-3373 (TNF-steroid ADC) ■ RINVOQ (JAK 1): Atopic Derm ■ ABBV-155 (BCL-xLi ADC): Solid Tumor ■ ABBV-599 (BTK/JAK): RA ■ RINVOQ (JAK 1): UC ■ ABBV-181 (PD-1): Solid Tumor ■ ABBV-599 (BTK/JAK): SLE ■ RINVOQ (JAK 1): GCA ■ ABBV-321 (EGFR ADC): Solid Tumor ■ Ravagalimab (CD40): UC ■ RINVOQ (JAK 1): AS ■ ABBV-368 (OX40): Solid Tumor ■ IMBRUVICA* (BTK): Solid Tumors ■ RINVOQ (JAK 1): Axial SpA ■ ABT-165 (DLL4/VEGF): Solid Tumor ■ VENCLEXTA* (BCL-2): MDS ■ SKYRIZI* (IL-23): CD ■ ABBV-621 (TRAIL): Solid/Heme Tumor ■ Teliso-V (cMet ADC): NSCLC ■ SKYRIZI * (IL-23): UC Recently Approved ■ ABBV-744 (BET): Heme Tumor ■ ABBV-8E12* (Tau): AD ■ SKYRIZI * (IL-23): PsA ■ RINVOQ: RA (US, EU, JPN) ■ ABBV-927 (CD40): Solid Tumor ■ Elezanumab (RGMa): MS ■ IMBRUVICA* (BTK): 1L cGvHD ■ SKYRIZI*: Ps (US, EU, JPN) ■ ABBV-CX-2029* (CD71): Solid/Heme Tumor ■ ABBV-2222/ABBV-3067 ■ IMBRUVICA* (BTK): 1L FL (CFTR-C1/CFTR-P): Cystic Fibrosis ■ VENCLEXTA*: 1L CLL (US) ■ ABBV-647* (PTK7 ADC): NSCLC ■ IMBRUVICA* (BTK): 1L MCL ■ ELAGOLIX* (GnRH): PCOS ■ IMBRUVICA* + Gazyva: 1L CLL (US) ■ ABBV-011 (SEZ6 ADC): SCLC ■ IMBRUVICA* (BTK): R/R MCL ■ VENCLEXTA* (BCL-2): ALL ■ IMBRUVICA* (BTK): R/R FL/MZL ■ VENCLEXTA* (BCL-2): Solid Tumor ■ IMBRUVICA* (BTK): 1L CLL ■ CCW702* (CD3-PSMA): Prostate Cancer ■ Veliparib (PARP): NSCLC ■ CLBR001/SWI019* (sCAR-T): Heme Tumor ■ Veliparib (PARP): BRCA Breast Cancer ■ TNB-383B* (CD3-BCMA): MM ■ Veliparib (PARP): 1L Ovarian Cancer Oncology ■ TTX-030* (CD39): Solid Tumor ■ VENCLEXTA* (BCL-2): 1L CLL Immunology ■ ABBV-0805* (a-Synuclein): PD ■ VENCLEXTA* (BCL-2): 1L AML ■ AL002* (TREM2): AD ■ VENCLEXTA* (BCL-2): AML Maintenance Neuroscience ■ AL003* (CD33): AD ■ VENCLEXTA* (BCL-2): R/R MM t(11;14) Other ■ ABBV-4083 (TylAMac): Filarial Diseases ■ Navitoclax (BCL-2/BCL-xL): Myelofibrosis ■ ABBV-951 (dopamine receptor): PD ■ ELAGOLIX* + Hormonal Add-Back (GnRH): Endometriosis

We continue to focus on the quality of our medicines, while doubling our early-stage pipeline since 2013, with more than 30 assets currently in late discovery and preclinical development As of February 7, 2020 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 17 *Partnered Asset; Partnership Summary Below: Imbruvica jointly developed and commercialized with Janssen Biotech; Elagolix developed in cooperation with Neurocrine Biosciences; Venclexta developed by AbbVie and Roche, commercialized by AbbVie and Genentech, a member of the Roche Group; Skyrizi developed in cooperation with Boehringer Ingelheim; ABBV-8E12 developed in cooperation with C2N Diagnostics; ABBV-0805 developed in cooperation with BioArctic; CCW702 / CLBR001 / SWI019 developed by Calibr in a first-in-patient trial and AbbVie holds option to license the program; TNB-383B developed by TeneoOne through Phase 1 and AbbVie holds exclusive right to acquire TeneoOne; AL002/AL003 developed by Alector through Phase 2 and AbbVie holds option for additional development and commercialization; TTX-030 developed by Tizona Therapeutics through Phase 1b and AbbVie has option to lead global development and commercialization; ABBV-2029 developed in cooperation with CytomX Therapeutics; ABBV-647 developed in cooperation with Pfizer. Anticipated key pipeline events

2020 2021 Regulatory IMBRUVICA ECOG Approval (1L CLL vs. FCR) IMBRUVICA 1L cGvHD RINVOQ PsA VENCLEXTA 1L CLL (EU) VENCLEXTA 1L AML (EU) RINVOQ AD Approvals Elagolix UF VELIPARIB 1L Ovarian Cancer RINVOQ AS VELIPARIB BRCA Breast Cancer Elagolix + Hormonal Add-Back EM Regulatory IMBRUVICA 1L cGvHD (iNTEGRATE) IMBRUVICA + VENCLEXTA r/r MCL (SYMPATICO) VENCLEXTA 1L AML unfit (EU) IMBRUVICA + VENCLEXTA 1L CLL (CAPTIVATE) Submissions Veliparib 1L Ovarian Cancer IMBRUVICA r/r FL/MZL (SELENE) Veliparib BRCA Breast Cancer ABBV-951 PD RINVOQ PsA SKYRIZI CD RINVOQ AD SKYRIZI PsA RINVOQ AS Navitoclax R/R MF Elagolix + Hormonal Add-Back EM Ph3/Registrational SKYRIZI Ph3 CD induction (MOTIVATE) IMBRUVICA Ph3 1L MCL (SHINE) SKYRIZI Ph3 PsA (KEEPSAKE2) IMBRUVICA Ph3 r/r FL/MZL (SELENE) Data Readouts SKYRIZI Ph3 Ps H2H vs Cosentyx IMBRUVICA + VENCLEXTA Ph3 r/r MCL (SYMPATICO) RINVOQ Ph3 PsA IMBRUVICA + VENCLEXTA Ph3 1L CLL (GLOW) RINVOQ Ph3 Atopic Derm VENCLEXTA + IMBRUVICA Ph3 1L CLL (CLL13) VENCLEXTA Ph3 AML unfit (VIALE-A; VIALE-C) VENCLEXTA Ph3 3L+ MM t(11;14) (CANOVA) IMBRUVICA + Venclexta Ph2 1L CLL (CAPTIVATE) ABBV-951 Ph3 PD IMBRUVICA Ph3 1L cGvHD (iNTEGRATE) Ph3/Registrational VENCLEXTA Ph3 AML fit VENCLEXTA Ph3 r/r MM t(11;14) w/ Darzalex VENCLEXTA Ph3 MDS VENCLEXTA Ph3 Solid Tumors Study Starts Navitoclax Ph3 1L and r/r MF SKYRIZI Ph3 AD SKYRIZI Ph3 UC SKYRIZI Ph3 HS Ravagalimab (ABBV-323; CD40) Ph3 UC Early-Stage ABBV-3373 (TNF/Steroid ADC) RA Ph2 ABBV-927 (CD40 Agonist) Ph1 ABBV-151 (GARP+TGF-β1) Ph1 ABBV-599 (JAK/BTK) RA Ph2 ABBV-368 (OX40) Ph1 ABBV-CX-2029 (CD71) Ph1 Data Readouts Ravagalimab (ABBV-323; CD40) UC Ph2 ABBV-647 (PTK7 ADC) Ph1 ABBV-599 (JAK/BTK) SLE Ph2 ABBV-157 (RORgt) Ps Ph1 ABBV-011 (SEZ6 ADC) Ph1 ABBV-8E12 (Tau) AD Ph2 Teliso-V (cMet ADC) Solid Tumor Ph2 TNB-383B (CD3-BCMA) Ph1 Elezanumab (RGMa) MS Ph2 ABBV-155 (BCL-xLi ADC) Solid Tumor Ph1 ABBV-321 (EGFR ADC) Ph1 ABBV-2222/ABBV-3067 (CFTR- TTX-030 (CD39) Ph1 C1/CFTR-P) CF Ph2 VENCLEXTA Solid Tumor Ph1 Elagolix (GnRH) PCOS Ph2 ABBV-621 (TRAIL) Ph1

Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer

Therapeutic areas Capabilities Vignettes

Immunology Medicinal Molecular • VENCLEXTA Chemistry Modeling • MAVYRET

Oncology

• Computational Genetics & Bioinformatics Genomics Immuno-oncology Virology • Genomics Research Center

Neuroscience Precision Innovation in • Development Medicine Clinical Trials Design Center

ABBV-467 MCL-1 Entering Phase 1

1. Apoptosis is a normal process 2.In cancer, BCL-2 family members 3.Compounds that block BCL-2 family can inhibit apoptosis members can induce apoptosis

Death Signals Death Signals BCL-XL Death Signals BCL-XL

BCL-2 BCL-2 BH3 BH3 BH3 MCL1 MCL1

Cell death Cell death Cell death survival

4. AbbVie scientists pioneered the discovery of BCL-2 family inhibitors and advanced the field of apoptosis for treating both heme and solid tumors

Although we generated preclinical data on which BCL-2 family members are linked to specific tumor types, our current understanding of which inhibitors work best in different indications has come from multiple clinical studies

Target Drug Preclinical insights Clinical insights Additional clinical insights BCL-2 VENCLEXTA Heme CLL, AML, MM (t11:14), Breast

BCL-XL + BCL-2 Navitoclax Heme and solid Myelofibrosis Solid tumor efficacy requires higher doses linked to platelet depletion BCL-XL ABBV-155 Solid Target indications to be ADC modality avoids (ADC with BCL-XL) determined in Phase 1 platelet effects

MCL-1 ABBV-467 Solid and heme Target indications to be determined in Phase 1

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 24 Discovery breakthrough Challenge: BCL-2 family considered “undruggable” given #1: Drugging a protein- the need to disrupt large, hydrophobic and high affinity protein interaction protein-protein interactions

• AbbVie medicinal chemists developed BCL-2 X-ray structure BCL-2 new technology and broke drug discovery rules to identify the first- generation BCL-2 family inhibitors BCL-XL • Our medicinal chemists discovered

Navitoclax, the first orally active “the groove” clinical BCL-2 family inhibitor • BCL-2/BCL-XL inhibitor is clinically active in myelofibrosis Navitoclax: Binds in the groove of BCL-2 and BCL-XL • Generated the first drug to inhibit

O a protein-protein interaction F3C S O H N S H H O N S O O N

O N Next challenge: BCL-2 selectivity N

• BCL-2 and BCL-XL are very similar proteins BCL-2 BCL-XL • Only four residues differ within binding groove of BCL-2 and BCL-XL

D100 E96

D108 A104 M112 R126 S122 L108

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 26 Discovery breakthrough #2: Analyses of the protein structure provided insights into selectivity and potency, leading to the discovery of VENCLEXTA

AbbVie scientists generated unique X-ray crystal structures, leading to structural insights that facilitated discovery of first-in-class BCL-2 selective inhibitors

Navitoclax • Remove “bent-back” BCL-2 and BCL-XL Inhibitor thiophenyl group (BCL-2 X-ray structure) • ↑BCL-2 selectivity, ↓potency

Structure- Based

Design ASP103 • X-ray shows amino acid VENCLEXTA (Trp) sidechain from First-in-Class neighbor BCL-2 protein Selective BCL-2 • Trp sidechain fills P4 Inhibitor pocket – makes BCL-2 selective H-bond with ASP103

O – F C O +O 3 S O N H O H N N S O H H O O N S S O NH BCL-2 Protein O O N O Structures O N N N H Sattler, Science 1997, 275: 983 N

N ABT-263 N ABT-199 (Navitoclax) (VENCLEXTA)

Cl Cl

Insights and innovations leading to the discovery of VENCLEXTA • Generation and full understanding of BCL-2 family member molecular structures • Development of new technologies (SAR by NMR) to enable discovery of protein-protein interaction inhibitors • Recognition of the role of BCL-XL in controlling the survival of circulating platelets • Persistent “art of the possible” medicinal chemistry effort to discovery orally bioavailable, selective BCL-2 inhibitors

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 29 Clinical challenge: The ability to increase potency and decrease resistance mutations was essential to create a two-drug next-generation HCV regimen

NS5A Homodimer Resistance MAVYRET is focused on two mutation protein drug targets, NS3 protease and NS5A, a protein of unknown function, but critical to viral survival Numerous companies had lead compounds at the time we began research on NS5A

NS5A is a symmetrical One key resistance mutation dimer critical for viral appears with all known NS5A life cycle, but of inhibitors at the time unknown function Attempts to discover a compound interacting with the resistance mutation were unsuccessful

Thinking differently, we went beyond established industry standards, abandoning the resistance mutation binding site Our modelers generated compounds that would affect the dimer Since the molecules are symmetrical, we Dimer interface evaluated the dimer interface and found a 90 degree rotation perfect binding site for symmetrical molecules

Based on this model we identified a novel binding pocket

Building into this pocket brought high potency, broad genotype activity and reduced resistance

Success factors: • Our scientists abandoned the resistance mutation binding site • Having atomic resolution protein structure allowed us to use structure- based drug design to model compounds

NS5A component of MAVYRET

MAVYRET is approved as a pan-genotypic 8-week treatment option for most HCV patients, supported by 98 percent cure rates (rates ranged between 92-100 percent)

Generation and Regulation Numerous Collaborations AbbVie Approaches of Antitumor Immunity with Leaders in the Field*

Emerging Areas: Suppressive Tumor Microenvironment e.g., anti-GARP antibodies, CD40 agonists

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

Calico

* Select collaborations

Oncology I-O Immunology

Protein Small Molecule Computational Rational Emerging New Engineering Therapeutics Biology Combinations Biology Technologies

Josue Samayoa David Masica Multidimensionally-defined tumor-immune Sr. Principal Scientist Principal Scientist landscape for HNSCC Ph.D.: University of Ph.D.: Johns Hopkins (based on RNAseq and IHC) California Santa Cruz University

Tolga Turan Tyler McLaughlin Principal Scientist Sr. Scientist Ph.D.: University of Ph.D.: Rice University California Irvine

Kyle Halliwill Zoltan Dezso Principal Scientist Principal Scientist Ph.D.: University of Ph.D.: Notre Dame University California San Francisco

Sarah Kongpachith Xu Shi Sr. Scientist II Sr. Scientist II Ph.D.: Stanford Ph.D.: Virginia Polytechnic Institute and State University

Th1 TCGA- BRCA

Effector

Immune

signaling

functions

regulatory

Chemokines CXCR3/CCR5

CXCL9 IFNG GNLY CD274 CXCL10 TBX21 PRF1 CTLA4 CCL5 CD8 GZMA FOXP3 IL12B GZMB IDO1 CD8 GZMH PDCD1 STAT1 IRF1

Hendrickx et al, Oncoimmunology 2017

TCGA/IGCC/Clinical trial RNA, DNA and methylome datasets

For each tumor type, we imputed: • Cell types • Pathways Drug target/ • Gene expression candidate

We prioritized these targets, both internally and externally Example Phase 1 program MOA Indication(s)

Triple I-O combo CD40, OX40, PD-1 NSCLC Defined paths to the clinic (ABBV-927+368+181)

TNBC, bladder, ABBV-151 GARP/TGF-β Clinical trial populations informed pancreatic, HNSCC by computational analyses (i.e. tumor types where target is “active”) ABBV-368/TLR9 combo OX40, TLR9, PD-1 HNSCC

TTX-030 CD39 Solid tumors Translational studies (biomarker MAVU-104 ENPP1/STING Solid tumors selection based on I-O hypotheses)

• TGF-b plays a role in establishing and driving immunosuppression in the tumor microenvironment by several mechanisms o Suppression of cytotoxic T lymphocytes, T helper 1 cells, natural killer cells and dendritic cells o Enhancing the number and functions of pro-tumor regulatory T-cells, M2-like macrophages, and myeloid-derived suppressor cells (MDSCs)

• GARP is a novel I-O target that is implicated in TGF-β biology • ABBV-151 prevents GARP-mediated TGF-β-1 suppression of T effector cells • ABBV-151 disables T regulatory cells and enables T effector cells

Role of Computational I-O team on ABBV-151 program: • Characterized target biology

• Guided disease indication selection Teffector (ex. cytotoxic T-cell) • Analyzed clinical trial biomarker data

Treg

Immune Presence

TGF-β Signaling

More likely to respond to PD1 treatment Less likely to respond to PD1 treatment

Genetics and genomics; New capabilities: Genetics and genomics; innovation in clinical trials innovation in clinical trials

Howard Jacob, Ph.D., Vice President and Head, Genomics Research Center

Kyle Holen, M.D., Head, Development Design Center

Howard Jacob, Ph.D., Vice President and Head of the Genomics Research Center

Target Lead Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Registration Launch Stage: Discovery Discovery • In medicine, knowledge % Success 63% 61% 64% 57% 56% 44% 60% 83% is estimated to be Overall doubling every 18 1.8% months Discovery Development • There must be a 24.5% 7% better understanding Figure1, Attrition Across the Pipeline.1 of pathobiology in these data

• How can knowledge Estimated Rate of Knowledge Doubling be doubling and pharma’s success rate staying constant? • There must be better ways to treat disease and manage healthcare with data

Nature Reviews Drug Discovery June 2016, Vol 15. pg. 379

The Genomics Research Center (GRC) Massive data sets from: Since 2016, we have invested in Six functional teams people, technology, and cohorts Supports all therapeutic areas • Real-world data (~350M claims) • Epigenetics Connects across R&D totaling over $100M to date • Large cohorts • Imaging

TA Disease AbbVie is acquiring over Biology o 10% of Finland • Wearables 1 million genomes o ~1% of Ireland • Longitudinal data Genomics is now impacting: o 500,000 UK biobank • EHRs: 150 million (globally) Best Therapies • Discovery in three core therapeutic o 30,000 cancer patients • Whole genome CRISPR screens TA Trans. TA Clinical areas Sciences Dev. in cell lines, iPCS from patients, • Whole genome sequencing and in vivo models • Development in all areas • Single-cell transcriptomics

• Process sciences to improve our Human CHO cells ability to make biologics genetics

Functional Pharmaco- • Governance starting in March 2020 genomics genomics • Today, we are working from the single patient with • Corporate Strategy: What deep phenotyping and molecular fingerprinting to indications, what targets, national level healthcare data what companies • Creating the need to re-think our data strategy and Bio-informatics Genome biology • Commercial: We are testing if pipeline Omics can be used to identify the Genomic technology best drug • Doubled the number of clinically validated targets IT Infrastructure (IR)

Oncology

Stratify Patients

Immunology Target ID and Confirmation

Population cohorts for new indications, New Indications, TNF example target ID and confirmation

Using >500,000 genomes to evaluate large numbers of targets in silico Increase accuracy and reduce time to identify

In vivo Syngeneic Tumor Cell Microglia Alzheimer IBD Target Discovery IO CRISPR Screens Disease Target Discovery

Immunology Oncology Neuroscience •Overview: Integrated genomics and •Overview: In vivo CRISPR screens •Overview: Human AD vs Mouse APP genomics approach to IBD target using multiple syngeneic tumor models transgenic – select targets from man and discovery (genome-wide CRISPR to identify tumor cell targets under back-translate screens, genome-wide association study immune surveillance •Outcome: sNuc/cell-Seq enables use of and clinical expression profiling) •Outcome: Feasibility demonstrated for archived human AD brains, major •Outcome: 3 new targets entering MC38 colon cancer model regulatory pathways identified immunology discovery pipeline •Status: Multiple new screens planned •Status: Target validation ongoing •Status: Additional target validation efforts for 2020; additional model development Static ongoing with human primary macrophage in progress and in vivo approaches

Disease Associated Mouse Transgenic Microglia with amyloid plaques

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 49 Innovation projects and new initiatives Epigenetics Image-based morphological CHOmics: SUPERCHO CRISPR screening profiling (cell painting) expression platform in single cells

• Identify functional target (gene/s) of • Multiple cellular features imaged • Collaboration with Process Science team • Link genotype to molecular phenotype sequence variant nominated from FinnGen simultaneously using fluorescent dyes at ABC (Operations S&T) at high throughput by mapping enhancers, promoters (ChIP- seq) and generation of 3D DNA interactions • Cellular signatures derived via automated • Leverage ‘omics platforms to improve • Utilize the conventional CRISPR/Cas9 with Hi-C,PLAC-seq feature extraction and machine-learning biologics product quality, yield, loss-of-function (LoF) screen assisted image analysis manufacture process • Deconvolute the genome-wide association • Couple with single-cell RNA-Seq study (GWAS) hits in patients with IBD by • Clustering of signatures to categorize • CHO lipase KO to support risankizumab (scRNA-Seq) utilizing ATAC-seq, Hi-C, PLAC-seq, phenotypically similar genetic or chemical production completed in 2019; unbiased Gene Transcriptome Molecular proteomics, and RNA-seq data from gut perturbations epigenetic characterizations, additional Perturbation Measurement Phenotype tissue samples in healthy individuals, gene editing and screening projects non-inflamed individuals, and in line for 2020 inflamed individuals

Deep mutational scanning Lenti-MPRA Linking non-coding Coordination center to (MITE-seq) variant to gene develop animal models

• Implement saturation mutagenesis approach • Functionalization of GWAS non-coding • Implement 3C (chromosome conformation • Utilizing knock-in, knock-out, CRISPR/Cas, to comprehensively assess the effect variants using lentivirus based massively capture) methods to link non-coding variants BAC transgenesis etc. 13 genetically of nonsynonymous mutations on BCL-2 parallel reporter assay (Lenti-MPRA) in (IBD GWAS) to their target genes in modified strains were delivered and 9 new and its role in development of resistance disease-relevant cells disease-relevant cell system one were started in 2019 to VENCLEXTA • POC with 225 SNPs in IBD overlapping with • Confirm/discover findings as it correlates H3K27Ac PLAC-seq data in Caco-2 cells, with novel mutations arising in the clinic 38 SNPs from PANTS anti-TNFα response/ non-response in Chr12 and 45 SNPs from FinnGen IBD GWAS Chr7 TNRC18 locus CLL patient mutation

Right biology Right target Right molecule Right dose Right patients

Target Target Lead Preclinical Lead Phase I and II Pivotal Discovery Validation Generation Optimization Development Trials

Leverage doubling of knowledge and manage knowledge half-life

• We can start our discovery pipeline with knowledge from human data o Real world data o EHR data or clinical trial data o Omics data o Molecular fingerprints • The ability to gene edit in the cell, tissue and animal has changed our discovery platform • Reduce our failure rates and accelerate the pipeline by using human data most of the time • Increase the effectiveness of our treatments • Move into new indications faster • Produce better biologics faster • Help physicians and patients use our medications

Becoming the best knowledge-based biopharma company

Kyle Holen, M.D., Head, Development Design Center

Growing AbbVie’s growing pipeline Pipeline demands efficiency and innovation

Drive The entire portfolio must have Consistency access to innovative tools and cross-therapeutic learning

Exceptional Big Data allows for predictive Tools analytics and machine learning: the future of AbbVie’s success

People Bring experts together as partners to drive the latest technology for optimal clinical output

Technology Process Leverage predictive Establish a common analytics and real-world approach to clinical data to strengthen trial design and optimize clinical decisions

We are consistently finding ways to leverage data and tools in combination to provide a more robust dataset for decision making

Custom code Site metrics Custom scripts allows us to combine study, site How quickly do they recruit? and investigator metrics. Start-up times? Retention? Is data quality an issue? NIH Study metrics New tools DQS What is the status of the trial? Are there new tool and data Does it share similar details to sources AbbVie should the proposed study? Who is consider? Where are the gaps in the sponsor? our collective knowledge? How will this fit into our toolbox?

Investigators TriNetX Patients Is the investigator still active? Do they have Who are the patients? How AbbVie experience? many exist? Where are they Are they gaining or located? How does this losing influence? relate to trial feasibility?

Accelerating Study Predicting Study Finding Patients Pre-diagnosis In Silico Control Arms Enrollment By Better Participants Who Drop-out Site Selection • We analyzed more than • By analyzing millions of patient • We used more than 4 million • We can predict patient placebo 11,000 patients with millions medical records, we can identify data fields from 10-15 responses in our clinical trials of data to better understand patterns of health care sources to better predict by using machine learning to factors associated with engagement that can predict highest performing sites develop outcome algorithms dropping out of a study a diagnosis • These models outperform • These algorithms can be used • Solving industry wide problem • These patients can then be historic performance by to predict how our patients of high drop out rates by using offered our clinical trial, or 5-7 months would have responded a risk score analysis perhaps an AbbVie treatment would they have not received that would benefit them our drugs

This machine learning model lead to a ~5 month acceleration of the clinical program

This machine learning model showed consistent improvements over using historical performance data

• The DDC worked with the study team for ABBV-621 (eftozanermin alfa or “Eftoza“) where time to proof of concept was critical • Analytical insights from the DDC were utilized to accelerate the study design and find the patients

Tokens Abbvie Design and Execution Direct-to-Patient Trials Personal identifiable information encrypted to create a unique code that can be used for anonymized research Platform (ADEPt) Gathering the building The first company in the industry Forecasting and trial blocks for virtual studies to utilize tokens for a 360 view simulation tool of participants in our trials

Patient Burden In Silico Controls Tech-Enabled Medicine “Bookshelf” Development

Developing a tool to measure Creating algorithms to Developing novel digital patient burden in our studies predict disease outcomes endpoints for our studies

Expansion of the pipeline Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer

Phase 1 Phase 2 Registrational / Phase 3 Submitted

We continue to focus on the quality of our medicines, while doubling our early-stage pipeline since 2013, with more than 30 assets currently in late discovery and preclinical development As of February 7, 2020 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 62 *Partnered Asset; Partnership Summary Below: Imbruvica jointly developed and commercialized with Janssen Biotech; Elagolix developed in cooperation with Neurocrine Biosciences; Venclexta developed by AbbVie and Roche, commercialized by AbbVie and Genentech, a member of the Roche Group; Skyrizi developed in cooperation with Boehringer Ingelheim; ABBV-8E12 developed in cooperation with C2N Diagnostics; ABBV-0805 developed in cooperation with BioArctic; CCW702 / CLBR001 / SWI019 developed by Calibr in a first-in-patient trial and AbbVie holds option to license the program; TNB-383B developed by TeneoOne through Phase 1 and AbbVie holds exclusive right to acquire TeneoOne; AL002/AL003 developed by Alector through Phase 2 and AbbVie holds option for additional development and commercialization; TTX-030 developed by Tizona Therapeutics through Phase 1b and AbbVie has option to lead global development and commercialization; ABBV-2029 developed in cooperation with CytomX Therapeutics; ABBV-647 developed in cooperation with Pfizer. AbbVie’s early target and preclinical portfolio snapshot As of February 7, 2020

Therapeutic Early Target Portfolio Late Discovery Portfolio Area Exploratory Hit Generation Lead Generation Lead Optimization Candidate Nomination &Selection Pre-Clinical ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●●● ●●●●● ●●● ●●●●●●●● ●●●●● ●●●● Immunology ●●●●●●●● ●●●●●●●● ● ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●●●● ●●●●●●●●●● ●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●● Oncology ●●●●●●●● ●● ●●●●●●●● ●●●●● ●●●●● ●●●●●●●● ●●●●● ●●●● Neuroscience ●●●●●●●● ●● ●●●●●●●● ●●●●●● ●● ●●●●● ●● ●● Calico

●● ●●●● Other ●

Proof of Concept (POC)1 Read-Out

2020 2021 2022

927 TNB- 011 321 621 CD40 184 467 CCW702* HPN-217* 383B* agonist Oncology 155 Teliso-V

CX- TTX- CLBR001 151 368 647* 189* 744 2029* 030* /SWI019*

599 Ravagalimab 599 Immunology 157 3373 CD40 RA SLE antag

Elezanumab Elezanumab Neuroscience MS Stroke, SCI 8E12* AL002* AL003*

2222/ Other 1882 3067

1. POC date corresponds to interim data readout; Only pipeline assets that have not already achieved POC represented *Partnered Asset: ABBV-647 developed in cooperation with Pfizer; ABBV-CX-2029 developed in cooperation with CytomX Therapeutics; TNB-383B developed by TeneoOne through Phase 1 and AbbVie holds exclusive right to acquire TeneoOne; TTX-030 developed by Tizona Therapeutics through Phase 1b and AbbVie has option to lead global development and commercialization; ABBV-189 developed in cooperation with Harpoon Therapeutics; CCW702 / CLBR001 / SWI019 developed by Calibr in a first-in-patient trial and AbbVie holds option to license the program; HPN-217 developed by Harpoon Therapeutics through Ph 1/2 and AbbVie has option to license worldwide exclusive rights; ABBV-8E12 developed in cooperation with C2N Diagnostics; AL002/AL003 developed by Alector through Phase 2 and AbbVie holds option for additional development and commercialization

Neil Gallagher, M.D., Ph.D., Chief Medical Officer and Vice President of Development Oncology

5-year Overall Survival (%) Opportunity 6 Pancreatic 9 9 HCC 18 19 • Improve survival NSCLC 23 27 Stomach 32 33 Ovarian 47 51 MCL 59 63 MCC 63 • Improve survival, especially for patients 65 in later lines/later stages of disease CRC 65 65 Cervical 66 68 ALL 68 75 Bladder 77 • Improve survival for sub-populations 83 HL 87 with high unmet need (e.g., metastatic 88 stage, TNBC in breast) Breast 90 92 • Improve safety, tolerability, QoL Prostate 98

Source: SEER (based on patients into 2015), STS = Soft Tissue Sarcoma; MCC = Merkel cell carcinoma

2 9 20+ 100+ approved oncology breakthrough investigational AbbVie sponsored products worldwide designations by compounds in clinical trials in the FDA to date the clinic 50 countries

Additional 300+ IIS ongoing

Apoptosis I-O Tumor Targeting

Cancer cells often lose their ability to I-O therapies seek to overcome the Tumor cells can be distinguished from undergo apoptosis, thereby promoting ability of tumor cells to evade elimination normal cells by way of protein antigens tumor cell survival by the immune system on their cell surface

A 20+ year commitment to apoptosis AbbVie scientists are investigating AbbVie scientists have developed novel research led AbbVie scientists novel approaches to manipulate the systems to uncover tumor selective to the discovery and approval of immune system antigens for both solid tumors and VENCLEXTA – validating apoptosis hematologic malignancies as a compelling, new approach to For example, we are using cutting-edge genomics technologies to understand treating cancer We are using novel biologics (drug how tumors suppress immune responses conjugates, CD3 bispecific) and We are now exploring other forms and to develop new I-O agents next-generation engineered T-cells of cell death as next-generation to target tumor antigens and avoid anticancer agents killing normal cells

Preclinical Phase 1 / Phase 2 Phase 3 / Registrational Submitted / Launched

■ ABBV-467 ■ ABBV-744 ■ VENCLEXTA (1L CLL, 1L AML, ■ VENCLEXTA (1L CLL US) AML maintenance, R/R MM ■ TNB-383B ■ IMBRUVICA + Gazyva (1L t(11;14), MDS) ■ CLBR001/SWI019 CLL US)

■ IMBRUVICA (1L CLL, R/R FL/MZL, Heme Heme tumors ■ HPN-217 R/R MCL, 1L MCL, 1L FL) ■ Navitoclax (Myelofibrosis)

■ ABBV-184 ■ ABBV-621

■ VENCLEXTA (ALL, solid tumors) Both ■ ABBV-CX-2029

■ ABBV-637 ■ Teliso-V ■ Veliparib (1L ovarian, BRCA ■ ABBV-CLS-579 ■ ABBV-927 breast, NSCLC)

Solid ■ ABBV-189 ■ ABBV-321 tumors ■ ABBV-647 ■ CCW702 ■ ABBV-368 ■ ABBV-155 MOA ■ ABBV-151 I-O ■ ABBV-011 Apoptosis ■ ABBV-181 Tumor Targeting ■ ABBV-165 ■ TTX-030

Myelofibrosis (MF): a malignant, life-threatening bone marrow disorder Constitutive • MF disrupts production of blood cells by JAK/STAT extensive scarring in the bone marrow • This leads to severe anemia, weakness, fatigue, and splenomegaly (spleen enlargement) Inflammatory • In MF, certain mutations (e.g., V617F) cytokines result in sustained signaling of the • Fatigue JAK/STAT pathway leading to increased • Cachexia cell division and growth • Pain • Thrombosis • The only approved class of therapies • Infection (JAK inhibitors) offers symptom relief, • Acute Leukemia with minimal impact on underlying Splenomegaly and transformation pancytopenia course of the disease Bone Marrow Fibrosis • Encouraging early indications of reduction in allelic burden

• JAK/STAT activating mutations drive Driving proliferation and an anti-apoptotic effect lesion via MCL-1 up-regulation JAK2 V617F ruxolitinib • JAK2 inhibitor ruxolitinib (Jakafi) + reduces JAK/STAT signaling navitoclax proliferation STAT3 • Combining navitoclax with ruxolitinib induces apoptosis in MPN cells, including malignant stem cells Pro-survival MCL-1 BCL-XL BCL-2

Eradication of myeloproliferative neoplasms (MPN) cells and malignant Pro-death BAK BAX BIM stem cells may enable spleen normalization, remodeling of fibrotic bone marrow and improvement of hematologic parameters Apoptosis

BCL-XL levels are elevated Dual BCL-2/BCL-XL inhibitors (ABT-263 and ABT-737) in cells with acquired synergize with JAK2 inhibitor (JAKi-I) to kill resistance to JAK2 inhibitors JAK2 V617F cell lines (SET-2 and HEL) and PV patient samples

Cell lines PV Patient Sample

TG-Res: resistant to JAK2 inhibitor (TG101209) Rux-Res: resistant to ruxolitinib

• SVR35 best on study: 43% (13/30)

• SVR35 at week 24: 30% (9/30) • 53% (16/30) of patients resolved palpable splenomegaly during study treatment • 25% (8/32) of patients demonstrated reduction in bone marrow fibrosis (local assessment) o 13% (4/32) with 1 grade reduction o 13% (4/32) with 2 grade reduction

Data cut: November 18, 2019. Percentages calculated on the basis of efficacy analysis set (N=30). Baseline is defined as the last non-missing observation collected on or prior to the date of the first dose of any component of study treatment. *Denotes patients with high molecular risk (defined by the presence of mutations within ASXL1, EZH2, IDH1/2, SRSF2, U2AF1).

Program MOA Indication(s) Opportunity Stage

• Best-in-class ABBV-621 TRAIL agonist 2L Mutant KRAS CRC • Phase 1 – expansion and combos pro-apoptotic agent

• First-in-class ADC BCL-XL SCLC, NSCLC and ABBV-155 delivering BCL-XL • Phase 1 – expansion and combos Inhibitor breast cancer as cargo

• Best-in-class ABBV-467 MCL-1 Inhibitor R/R AML combination with • Entering Phase 1 VENCLEXTA

• Focus on targets that complement VENCLEXTA and IMBRUVICA resistance mechanisms Discovery • Pursue exploratory targets in under-explored forms of regulated cell death (e.g., necroptosis, ferroptosis)

BCL-XL Inhibitor BCL-XL inhibition induces apoptosis X-ray structure • We used structure-based design to discover first-in-class highly potent, selective BCL-XL inhibitors • Pre-clinical efficacy in solid tumors • In clinical studies with navitoclax, we observed platelet decreases at doses that are sub-optimal for treating solid tumors ADC technology used to deliver BCL-XL inhibitors to tumors • Generation of novel enabling linkers allowed for first-ever ADCs possessing BCL-2 family inhibitor warheads • ADCs show preclinical efficacy in mouse models of human lung Structure-Based cancer, with no platelet effect Design ABBV-155 is a First-in-Class BCL-XL inhibitor ADC • Currently in Phase 1 for solid tumors that express B7H3, which is expressed at high levels on many tumor cells but not platelets Novel Linker • Differentiated safety vs cytotoxic ADCs in monkeys Modified Antibody BCL-XL Inhibitor

Subject with KRAS CRC with • Novel TRAIL agonist with a pair of trimerized MT receptor binding domains that optimize clustering confirmed PR, sustained for 200+ days after 3 prior lines of therapy of TRAIL receptors independent of Fc engagement, ABBV-621 resulting in apoptotic cell death 127-mm baseline target

• Phase 1 study in multiple tumor types, dose

optimization in pancreatic cancer and KRASMT CRC baseline baseline change (%) • Encouraging preliminary monotherapy activity - (including PRs) in KRASMT CRC (see panel at right)

triggered expansion in 2L setting in combination best post with FOLFIRI

• cPOC study initiated Q4 2019; targeting interim analysis for early cPOC declaration by end of 2021

• Anchor potential for AbbVie through ongoing study in CRC as well as potential expansion into myeloma based on encouraging preclinical combination data

-1 1.E+12 Tumor load (#p*s ) ABT-199 50 mg/kg, QDx21 • MCL-1 is widely expressed in heme vehicle vehicle Day 31 MCL-1 and solid tumors; allows cancer cells 1.E+11

to evade apoptosis 1.E+10 A-1726694 Restoration of apoptosis through MCL-1 inhibition 12.5 mg/kg, Q7Dx3 • Mechanistic synergy between BCL-2 1.E+09 B C ABT-199 MCL-1 + ABT-199 MCL-1 inhibitor and MCL-1 inhibition across broad 1.E+08 BCL-2 + MCL1i array of MM, AML and NHL 1.E+07

A-1726694 Apoptosis 1.E+06 initiation + ABT-199 A D E • In vivo efficacy observed across 1.E+05 multiple preclinical models, both 0 10 20 30 40 50 MCL-1 BIM Period after inoculation (days) Pro-apoptotic BAX as monotherapy, and in combination proteins Preclinical Docetaxel-Resistant BAK with VENCLEXTA Cancer Cell Death BAX NSCLC Model (H1650-DTXr) Activation • IND approved Q4 2019, of caspases on target for FSFD Q1 2020 Cytochrome c • Anchor potential for AbbVie through MCL-1 inhibitor binds to MCL-1, freeing pro-apoptotic proteins that initiate key cPOC combination studies in MM programmed cell death (apoptosis). and AML

Program MOA Indication(s) Opportunity Next Data Milestone

Anti-cMET ADC First-in-class ADC targeting Teliso-V NSCLC • 2020: Go/No go registration trial decision Warhead: auristatin cMET

Anti-PTK7 ADC First-in-class ADC targeting ABBV-647 Ovarian, NSCLC Warhead: auristatin PTK7 • Phase 1: Ongoing • EOY 2021: If warranted by clinical data, cPOC early declaration Anti-SEZ6 ADC First-in-class ADC targeting ABBV-011 SCLC Warhead: calicheamicin SEZ6

First-in-class ADC SCLC, NSCLC ABBV-155 BCL-XL Inhibitor delivering BCL-XL • Phase 1 – expansion and combos and breast cancer as cargo

ADC strategy to focus on targets with higher tumor cell expression using warheads with intrinsic tolerability and novel Discovery mechanisms

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 78 Leverage strengths in ADCs, novel target identification and engineering of biologics to develop therapies that profoundly impact tumor cell fate

Example: Teliso-V Example: ABBV-647

Teliso-V is a cMET-targeted ADC ABBV-647 is a PTK7-targeted ADC • Expressed in many tumor types: NSCLC, gastroesophageal • Expressed in many tumor types: Ovarian, adenocarcinoma, papillary renal cell carcinoma, ovarian, NSCLC,TNBC, others melanoma, etc. • Safety: Manageable side effects in Phase 1 • Safety: Well-tolerated in patients who have received multiple prior lines of therapy • Efficacy: Promising Phase 1 clinical activity in heavily treated patients • Efficacy: Promising Phase 1 clinical activity in monotherapy and combo with erlotinib in patients with an EGFR mutation • Potential for cPOC by EOY 2021: • Potential for cPOC by 2020 o As monotherapy in NSCLC and/or ovarian o As monotherapy in NSCLC o Many lifecycle management options (e.g., I-O combos) o Potential combination strategy with osimertinib in EGFR- mutant NSCLC

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 79 We have a growing I-O 1. Modulation of Tumor Microenvironment pipeline Program MOA Indication(s) Triple I-O combo CD40, OX40, PD-1 NSCLC Pursuing two broad areas in I-O (ABBV-927+368+181) TNBC, bladder, ABBV-151 GARP/TGF-b pancreatic, HNSCC

ABBV-368/TLR9 combo OX40, TLR9, PD-1 HNSCC TTX-030 CD39 Solid tumors MAVU-104 ENPP1/STING Solid tumors

2. Use Immune Cells as Antitumor Weapons Program MOA Indication(s) ABBV-184 TCR Peptide-CD3 NSCLC T-cell redirection ABBV-189 TCR Peptide-CD3 NSCLC T-cell redirection TNB-383B BCMA-CD3 R/R multiple myeloma T-cell redirection HPN-217 BCMA-CD3 R/R multiple myeloma T-cell redirection sCAR-T Multiple targets Multiple Next-gen cell therapy

• ABBV-151 targets GARP/TGF-β a key immune- suppressive pathway activated in tumors

• Helps disrupt suppressive tumor microenvironment – thought to profoundly enhance antitumor activity of PD-1

• Compelling/robust pre-clinical data

• Phase 1 in combination with ABBV-181 in multiple solid tumors: TNBC, pancreatic, bladder, HCC, HNSCC

• First patient was dosed in 1Q19: 47 days post IND clearance

Why CD3 bispecifics can lead to transformative efficacy comparable to that seen from cell therapies but without the accompanied complexity

Goals Develop a world class CD3 platform that enables first-in-class or best-in-class CD3 bispecifics to cPOC every year starting 2021 targeting both heme and solid tumors

Liabilities Current generation CD3 bispecifics are limited to a restricted number of targets, efficacy only in heme malignancies, short half-life and inherent safety issues (cytokine release syndrome)

AbbVie CD3 Bispecific

CD3 tumor Tumor CD3 Binding Antigen antigen Domain Binding Domain

Tumor Cell Immune Cell Redirected Cell Killing

Optimizing platforms for clinical success Balancing validated vs less validated targets & tumors

Immune Cell 1 Immune Cell Type 2 3 Half-life 4 Targets 5 Tumor Type Binding Affinity

T-cell High Longer Clinically validated Clinically validated ABBV-184 ABBV-184 ABBV-184 BCMA, CD38 Heme malignancies ABBV-189 ABBV-189 ABBV-189 TNB-383B HPN217 HPN217

Novel targets, novel Solid tumors TriNKETTM TNB-383B technologies (TCRs) NK Cells Low Shorter More novel More novel

Preclinical Phase 1 / Phase 2 Phase 3 / Registrational Submitted / Launched

■ ABBV-467 ■ ABBV-744 ■ VENCLEXTA (1L CLL, 1L AML, ■ VENCLEXTA (1L CLL US) AML maintenance, R/R MM ■ TNB-383B ■ IMBRUVICA + Gazyva (1L t(11;14), MDS) ■ CLBR001/SWI019 CLL US)

■ IMBRUVICA (1L CLL, R/R FL/MZL, Heme Heme tumors ■ HPN-217 R/R MCL, 1L MCL, 1L FL) ■ Navitoclax (Myelofibrosis)

■ ABBV-184 ■ ABBV-621

■ VENCLEXTA (ALL, solid tumors) Both ■ ABBV-CX-2029

■ ABBV-637 ■ Teliso-V ■ Veliparib (1L ovarian, BRCA ■ ABBV-CLS-579 ■ ABBV-927 breast, NSCLC)

Solid ■ ABBV-189 ■ ABBV-321 tumors ■ ABBV-647 ■ CCW702 ■ ABBV-368 ■ ABBV-155 MOA ■ ABBV-151 I-O ■ ABBV-011 Apoptosis ■ ABBV-181 Tumor Targeting ■ ABBV-165 ■ TTX-030

Lisa Olson, Ph.D., Vice President Immunology Discovery

Immunology

3 11 94 17 approved disease areas ongoing clinical candidates in our immunology currently studied in trials in over 50 late discovery products worldwide clinical trials countries portfolio

We stand on a strong foundation and are building our future beyond one brand with groundbreaking new medicines

Clinical goals: Scientific goals:

Rheumatology: Rheumatoid arthritis and lupus • Molecular understanding of disease pathology • Identification of new pathways and targets from a Achieve durable remission and halt disease progression convergence of molecular data and clinical response • Patient stratification becoming a reality Dermatology: Psoriasis and atopic dermatitis Achieve clear skin with durable response with an oral agent Technological goals: Precise immunomodulation Gastroenterology: Crohn’s disease and ulcerative colitis Specifically targeting immune dysfunction to deliver greater clinical Improve clinical remission rates and induce efficacy and improved safety mucosal healing

Fibrosis: Scleroderma, IPF Achieve transformational efficacy by stopping fibrosis and reversing established extracellular matrix Antibody-Drug Targeted Local Delivery of Targeted Conjugates (ADCs) cytokines Small Molecules combinations

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 87 Utilization of the ADC technology for immune- mediated diseases Payload required improvements Linker in linker stability and payload potency mAb

1 112 200 Monoclonal Linker Steroid antibody combinations payloads

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 88 Why combine anti-TNF and steroid into an ADC? Systemic steroid effects all tissues • Anti-TNF antibody and steroid therapies are very effective medicines and are used in many diseases including RA, OH O IBD and psoriasis • They are often used in combination HO OH but the use of steroids is limited to Arthritic Joint H Bone short duration or low doses due to H H severe side effects O • AbbVie discovered that anti-TNF mAB is internalized on activated immune cells through its binding to transmembrane TNF • The anti-TNF ADC will direct the steroid payload directly to inflammatory cells CNS Skin

GI/Endocrine

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 89 Why combine anti-TNF and steroid into an ADC? TNF ADC targets inflamed tissue • Anti-TNF antibody and steroid therapies are very effective medicines and are used in many diseases including RA, IBD and psoriasis

OH • They are often used in combination O HO OH but the use of steroids is limited to Arthritic Joint H H H Bone short duration or low doses due to O severe side effects • AbbVie discovered that anti-TNF mAB is internalized on activated immune cells through its binding to transmembrane TNF • The anti-TNF ADC will direct the steroid payload directly to inflammatory cells CNS Skin

GI/Endocrine

Hypothesis: Targeting activated immune cells with the anti-TNF-steroid ADC will demonstrate durable inhibition of inflammation with no steroid side effects

Targeted steroid release

ADC Double staining with anti-TNF and K562 GRE reporter assay Lysotracker in LPS stimulated macrophages

Lysosome

Endosome Steroid Nucleus

Anti-inflammatory cascade

GRE, glucocorticoid responsive element; LPS, lipopolysaccharide; tmTNF, transmembrane TNF

1 .0 V e h ic le )

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92 Systemic glucocorticoid safety translated from preclinical species to humans

Preclinical Clinical

Anti-TNF ADC demonstrates comparable Systemic glucocorticoid safety: ABBV-3373 did not efficacy to high-dose steroid without side effects impact serum cortisol at 100 and 300 mg SC doses

Mean+SD AbbVie Data on File. Post-dose on Day 1 or Day 5 Time-matched % Change from Day -1 Baseline

Rheumatology Dermatology Gastroenterology RA, PsA & Others Hidradenitis suppurativa Crohn’s disease | Ulcerative colitis

Achieve durable remission and Achieve full skin clearance Improve clinical remission rates halt disease progression with durable response and induce mucosal healing

Phase 2 readout in RA expected in 2020

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 94 Anchored by the success of the anti-TNF-steroid ADC, Myeloid Cell Targeting the next generation Monocyte Dendritic Cells pDC iADC platform Macrophage Lymphocyte Targeting Targeting only Cells within strategy involves T-cells B Cells the Inflamed Tissue more selectively Dendritic cells targeting pathogenic

Macrophages immune cells TNF-Steroid ADC Level of Selective Expression and T-cells B Cells Potential Immuno- T-cells Dendritic Cells Macrophages Suppression Plasmacytoid PMNs Dendritic Cells Fibroblasts

NK Cells

Epithelial Cells

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 95 ABBV-599 (combination of ABBV-105 and upadacitinib) Designed to inhibit two distinct signaling pathways involved in the pathogenesis of immune-mediated inflammatory diseases

ABBV-105* Upadacitinib Inhibitor Bruton’s tyrosine kinase (BTK) Janus kinase (JAK) inhibitor with greater selectivity for JAK1 +

Inhibits B-cell proliferation and Myeloid cell Inhibits T-cell activation and multiple cytokine signalling molecules including IL6,& IFNg activation via FcRg

• Hypothesis: Inhibition of BTK and JAK signaling will result in superior efficacy for difficult-to-treat immune mediated diseases • Currently in Phase 2 development for rheumatoid arthritis and lupus

• Entering Phase 2 in scleroderma *ABBV-105 molecule not based on the actual molecular structure

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 96 ABBV-599: JAK1/BTK in Phase 2 in RA Hypothesis: Combining inhibitors of JAK1 and BTK will confer improved efficacy in autoimmune disease due to their independent and relevant mechanisms

JAK1 inhibition blocks common Combining JAK inhibition with BTK inhibition JAK and BTK pathways γ-chain and IL-6 signaling confers additive efficacy in rat CIA BTK and JAK Synergydo not Effects overlap on B Cell Proliferation (Human B Cells, BSC# M2131) IL-2, 4, 7, 9, 15, 21 IL-6 100 8000 B-cell proliferation ABBV105 ABBV105 (A-1519938.0) 80 ABBV105 + 5mg/kg ABT317 ABBV105 + 10uM ABT-317 6000 5mg/kg ABT317 ABBV105 + 1uM ABT-317 Transform of day60 last ABBV105 + fixed ABT317 study #2 JAKi ABBV105 + 0.1uM ABT-317 100 40 4000 ABT-317 (A-1190453.0)) ABBV105 day last day BTK inhibitor 80 ABBV-105 + ABT-317 20 Combination 2000

IL-15 inhibition IL-6 inhibition 5mg/kg ABT317 3H-TdR Incorporation 3H-TdR % inhibition of AUC of % inhibition JAK inhibitor (ED ) BTKi shows efficacy shows efficacy in 60 0 50 Combo in RA RA (Actemra) last)(day volume

% inhibitionpaw D % 0 40 0 0.01 0.1 1 10 100 0.0001 0.001 0.01 0.1 1 10 100 day last day uM Compound 20 ABBV105BTK inhibitor (mg/kg) IC50 BTK inhibition impacts B-cell AUC of % inhibition (mg/kg)Dose IL-6 induced pStat3 and myeloid cell populations 0 ABBV105 (A-1519938.0) 0.01034 ABBV105 + 10uM ABT-317 0.01640 0 0.01 0.1 1 10 100 ABBV105 + 1uM ABT-317 0.01092 ABBV105% inhibition (mg/kg) of paw swelling ABBV105 + 0.1uM ABT-317 0.01143BTKi A-1190453.0 (ABT-317) >10uM4.909 ABBV-105 ED = 0.6mg/kg Combination50 Mono Combo ABBV-105 + 5mg/kg ABT-317 ED50 = 0.1mg/kg JAKi JAK + BTK 50 >80 Combo

Phase 2 RA study will read out in 2020

Failure to receive appropriate Low levels of remission Improved outcomes demonstrated targeted treatment and endoscopic improvement with Mucosal Healing

Abdominal pain, frequent bowel movements and fatigue Endoscopically normal Cycling of conventional therapies tissue SESCD ≤ 2

Systemic 5-ASAs Corticosteroids Endoscopically inflamed tissue SESCD ≥ 3

Immunomodulators Probability of no relapse no of Probability Remission

Damage Accumulates

Months from baseline endoscopy

Naganuma, Digestion 93:55-71 (2016)

Compromised barrier function, aberrant responses to bacteria

Therapeutic approach: MOAs that drive mucosal healing

Microbes Mucus

IL-22 IEL Increased permeability

Peyer’s Patches T-cells Neutrophils Production Macrophages Th1 of IL-23, Th2

Lamina Propria Epithelium Mucous Lumen Epithelium Mucous Lamina Propria TNF, IL-6 B cells

Monocytes Expansion of lamina propria Cell Migration Treg

Th17 Dendritic cells Muscularis mucosa

Immune dysregulation Mesentari c Lymph Therapeutic approach: cytokine Blood Vessel Node inhibitors, myeloid targets, Tcells

• EP4 is a 7-transmembrane GPCR o One of four EP family members (EP1,2,3,4) o PGE2 is native agonist ligand o Highly expressed in colon

Human Whole Blood- LPS-induced TNF Human Organoids: Ki67 Histology

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Anti-inflammatory Mucosal Healing

Injection of Takedown anti-CD40 agonist Day 0 Day 6 Day 7 Start DSS CLE scoping Takedown Day 2 Day 7 MUC2-zsGreen Day -1 Day 0 mice

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f • Significant vascular leakage, • Vascular pattern o

erosions, goblet cell loss intact, no leakage or % 0 • Goblet cell morphology erosions detected N a i v e V e h ic l e E P 4 ( AEP4- 1 5 8 1 3 7 4 ) a n t i- T N F a is altered • Goblet cells show normal agonist6 0 m p k60 1 5 m p k mpk distribution and morphology N a ïv e V e h (P B SE)P 4 A-1 5 8 1 3 7 4 ) 6 0 mTp Nk F a -1 5 m p k

• Immunology Discovery has invested deeply in understanding the molecular drivers of human immune-mediated diseases in the rheumatology, dermatology and gastroenterology areas • Leveraging that knowledge, we have built a portfolio of assets that are focused upon delivering transformational efficacy • Targeting activated immune cells with the anti-TNF–steroid ADC will demonstrate durable inhibition of inflammation with no steroid side effects • Inhibition of two independent inflammatory pathways, JAK and BTK, will deliver increased levels of durable remission • We believe that healing the mucosal barrier of the inflamed GI tract is an essential component of achieving higher levels of clinical remission in IBD • EP4 agonism is one approach that demonstrates both anti-inflammatory and mucosal healing responses • We’re exploring novel approaches that may take us into areas, such as lupus and scleroderma

Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer

Neuroscience

High unmet need

Alzheimer’s disease Parkinson’s disease Multiple sclerosis

Increasing understanding in underlying biology

Pathological proteins Proteostasis Neuroinflammation Neural protection

tau α-synuclein

Alzheimer’s disease Parkinson’s disease MS and others Near-term Symptomatic opportunities Therapies

• ABBV-951 (L-dopa and carbidopa prodrugs)

Disease Modifying Disease Modifying Neurorestorative Therapies Therapies Therapies Longer-term opportunities • ABBV-8E12 (anti-tau) • ABBV-0805 • ABT-555 (anti-RGMA) • AL-002* (TREM2) (anti-alpha synuclein) • AL-003* (CD33) • Discovery Programs • Discovery programs

* upon agreement/option exercise

Majority of advanced PD patients are ~463,000 not adequately inadequately controlled on oral therapy controlled on orals

1% 1% 12%

Orals DBS 86% D/D Stay on Apo Orals

• With disease progression, gastric motility is impaired, making levodopa absorption from pills unpredictable • With oral therapies, levodopa levels vary prominently: trough concentration leads to OFF time and peak concentrations lead to dyskinesia • Providing a continuous, consistent and predictable amount of levodopa is key to controlling symptoms

ABBV-951 PK Data Compared to Oral LD/CD (+SD) AbbVie chemistry delivered innovative syntheses in Healthy Volunteers of both foslevodopa and foscarbidopa

Foslevodopa Foscarbidopa

Subcutaneous administration

The synthesis of foslevodopa and foscarbidopa resulted in: • A water-soluble prodrug that converts to levodopa in the subcutaneous space • High prodrug solubility and concentration allowing lower dose volumes enabling subcutaneous delivery via a small pump • The ability to individualize the dose ABBV-951 demonstrated low plasma variability, potentially able to • Good tolerability in advanced PD patients maintain levodopa exposure within a narrow therapeutic window. This is not possible with oral immediate release levodopa

2018 2019 2020 2021 2022 2023

Commercial Drug Delivery System Development

Ph1 SAD

Ph1b

Pivotal Study #1

Pivotal Study #2

Pivotal Study #3

Intra-cellular protein misfolding and aggregation Propagation correlates with neuronal loss and functional decline Functional proteins One abnormal Abnormal protein Eventually large toxic Stages I - II with normal structure protein forms acts as a template aggregates form

Stages III - IV

Propagation dendrites synapse axon

Stages V - VI

Therapeutic strategies: Prevent/remove aggregates, prevent propagation/uptake

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 110 AbbVie’s neuroscience pipeline is focused on processes that are strongly supported by genetic and mechanistic discoveries of the last decade

Pathological proteins Proteostasis Neuroinflammation Neural protection

tau α-synuclein

Tau: Preclinical AL002: agonist mAb targeting TREM Elezanumab: anti-RGMa mAb • We are exploring multiple approaches • Failure of proteostasis leads to the • In Phase 1 for AD • In Phase 2 for MS, SCI (2Q20) and for tau formation of toxic protein aggregates stroke (Q2 2020) • Our most advanced is ABBV-8E12, • Biology has provided a diversity of AL003: antagonist mAb targeting CD33. which is in Phase 2 targets that have high preclinical • In Phase 1 for AD • RGMa blockade with monoclonal • Other approaches include higher in vivo validation antibody elezanumab enhances affinity Ab’s that are selective for • Most advanced approach targets • ~1/3 GWAS hits associated with late repair and promotes functional pathogenic/aggregated tau, AAV- intracellular aggregates and onset Alzheimer’s disease are recovery in numerous preclinical delivery, degradation facilitates rapid clearance expressed in microglia injury models Anti-α-synuclein: Preclinical • ABBV-0805 antibody, binds fibrillar α- • Single cell transcriptome analyses synuclein with nM affinity and high revealed novel pathology-associated selectivity vs monomeric protein, microglia target genes in human currently in Phase 1 for PD Alzheimer’s disease • Other approaches currently focused on selectivity to pathogenic a-syn

CD33 AL003 AL002 TREM2 • Receptor on the surface • Receptor on the surface of microglia antagonist agonist of microglia

• Human genetic variants • Human genetic variants associated with AD associated with AD

• Activation converts • Activation converts microglia into a more CD33 TREM2 microglia into a more neurotoxic form neuroprotective form

AL002 and AL003 currently in Phase 1b trials for AD

‘Neurotoxic’ Neuroprotective/ homeostatic

Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer

Cystic fibrosis

AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 113 Cystic fibrosis: Rationale and status AbbVie molecules • While recognizing that Vertex is the market leader, we believe that it is feasible to bring forward assets that will give meaningful benefits CFT R to CF patients

Vertex’s Trikafta ABBV-3067 • 20% of patients have an FEV1 improvement of 5% or less CI (Potentiator) – Next-Gen Correctors • safety / tolerability liabilities: elevated liver enzymes, Golgi (C2 Corrector) cataracts, DDI, GI ABBV-2222 Proteosome (C1 Corrector) Endoplasmic • Our data support the notion that the efficacy ceiling has not been met F508del reticulum and safety/tolerability/dosing profiles can be improved Nucleus • We have preclinical data with AbbVie compounds that could achieve a transformational response (> 18% FEV1)

AbbVie Triplet • C1 Corrector ABBV-2222: Best-in-class AbbVie triplets show full restoration of fluid • • Two potentiators ABBV-3067 and ABBV-191 • C2 Corrector: ABBV-119 IND submission Q2 2020 homeostasis • ABBV-2222+ ABBV-3067 doublet in Phase 2

• AbbVie is the only competitor with quality assets for all MOAs

Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer

Calico

• Founded in September 2013 by Google and Art Levinson (CEO) • Launched unique, 10-year collaboration with AbbVie in September 2014 • In 2018, extended by 3 years to 2027, with significant funding enabling long-term view • Mission: Increase understanding of the biology of aging and harness advanced technologies to bring therapies to market in aging-related diseases, including neurodegeneration and oncology • Extensive external network of scientists and >30 sponsored research agreements with 22 leading Institutions that provide novel targets, additional resources, or capabilities for some collaboration programs

• AbbVie and Calico scientists partner throughout the drug discovery process • AbbVie option triggers with Phase 2a data/clinical proof of concept

SCIENTISTS 13 YEARS 400+ CLINICIANS 44+ TARGETS 2 PROJECTS

Collaboration RUNWAY At ABBVIE and CALICO In the Joint PORTFOLIO In CLINICAL TRIALS by 2020

The portfolio is split between oncology and neurodegeneration

Current 26 Jan 2020

Oncology/I-O • Target Biology/Hit Discovery: n=26 • Lead Generation/Optimization: n=1 • Preclinical: N=2 • Clinical: 1 program to Phase 1 FIH (2020)

Neurodegeneration • Target Biology/Hit Discovery: n=13 • Lead Generation/Optimization: n=5 • Preclinical: N=1 • Clinical: 1 program to Phase 1 FIH (2020)

Mike Severino, M.D., Vice Chairman and President

Early Target Portfolio Late Discovery Portfolio Clinical Development Therapeutic Candidate Lead Area Exploratory Hit Generation Lead Optimization Nomination Pre-Clinical Phase 1 Phase 2 Phase 3 Generation & Selection

Immunology 33 13 12 9 5 3 2 6 11

Oncology 45 26 20 10 10 7 18 3 13

Neuroscience 5 18 5 4 3 2 1

Other 1 2 4 1 2 1

Calico 8 6 2 5 2 2