Abbvie Inc. · NYSE:ABBV
Abbvie — Investor Day (March 2020)
122 slides from Abbvie's investor day presentation, Mar 10, 2020
Slide 1: AbbVie R&D Deep Dive
AbbVie R&D Deep Dive March 10, 2020
Slide 2: Forward-Looking Statements and Non-GAAP Financial Information
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 expression
Slide 3: Evolution of AbbVie R&D
Evolution of AbbVie R&D Evolution of AbbVie R&D Mike Severino, M.D., Vice Chairman and President AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 3
Slide 4: We have consistently increased R&D investments and productivity since inception
We have consistently increased R&D investments and productivity since inception 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
Slide 5: Revenues from products launched since inception are growing robustly
Revenues from products launched since inception are growing robustly 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 AbbVie Sell-Side R&D Deep Dive | March 10,
Slide 6: AbbVie's recently launched medicines will expand into new disease areas
AbbVie’s recently launched medicines will expand into numerous important new disease areas Current Approved Indications Future Disease Areas • Psoriasis • Psoriatic arthritis • Crohn’s disease • Ulcerative colitis • Rheumatoid arthritis • Atopic dermatitis • Crohn’s disease • Psoriatic arthritis • U
Slide 7: We have built a healthy and productive pipeline
We have built a healthy and productive pipeline Existing Therapies Expanding Anticipated POC Readouts Launching New Assets into Important New Areas from Early-Stage Pipeline • ABBV-3373 (TNF/steroid ADC) RA Ph2 Navitoclax • ABBV-599 (JAK/BTK) RA Ph2 PsA AD CD HS • Current therapies provide symptom r
Slide 8: Our early-stage pipeline will drive additional growth in oncology
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 in
Slide 9: Our leadership in immunology will drive indication expansion
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 t
Slide 10: Our neuroscience research focuses on novel disease modifying therapies
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. Park
Slide 11: Our R&D organization has evolved significantly since 2013
Our R&D organization has evolved significantly since 2013 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 clinical trial simulation
Slide 12: We have R&D sites across the globe
We have R&D sites across the globe with an expanded presence on the east and west coasts North Chicago, IL Ludwigshafen, Germany East Coast, MA West Coast, CA Tokyo, Japan AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 12
Slide 13: Our top talent has allowed us to build industry-leading capabilities
Our top talent has allowed us to build industry-leading capabilities in important scientific areas 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 Medi
Slide 14: Key R&D leadership recruited since inception
Key R&D leadership recruited since inception 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 Scie
Slide 15: Our leaders have deep expertise in therapeutic areas and key capabilities
Our leaders have deep expertise in therapeutic areas and key capabilities Oncology Immunology Neuroscience 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, St
Slide 16: AbbVie R&D Pipeline - 2013
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 ■ HU
Slide 17: AbbVie R&D Pipeline - 2020
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):
Slide 18: Anticipated key pipeline events
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 R
Slide 19: Existing and new capabilities
Existing and Existing and new capabilities new capabilities Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 19
Slide 20: Our existing and new capabilities drive results
Our existing and new capabilities drive results Therapeutic areas Capabilities Vignettes Immunology Medicinal Molecular • VENCLEXTA Chemistry Modeling • MAVYRET Oncology • Computational Genetics & Bioinformatics Genomics Immuno-oncology Virology • Genomics Research Center Neuroscience Precision Inno
Slide 21: Discovery of VENCLEXTA: Breakthrough in drugging protein-protein interaction
Discovery of VENCLEXTA: Breakthrough in drugging protein-protein interaction AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 21
Slide 22: Multiple innovations led to AbbVie's leadership in apoptosis portfolio
Multiple innovations led to AbbVie’s leadership in developing an industry-leading apoptosis portfolio ABBV-467 MCL-1 Entering Phase 1 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 22
Slide 23: Building a portfolio of apoptosis tools and therapeutics
Building a portfolio of apoptosis tools and therapeutics 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 Death Signals BCL-XL BCL-XL BCL-2 BCL-2 BH3 BH3 BH3 MCL1 MC
Slide 24: Lessons learned in our journey to drug apoptosis
Lessons learned in our journey to drug apoptosis 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 i
Slide 25: Discovery breakthrough #1: Drugging a protein-protein interaction
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 BCL-2 X-ray structure new technology and broke d
Slide 26: Quest for BCL-2 selective agents
Quest for BCL-2 Challenge: Homology of BCL-2/BCL-XL binding selective agents groves presents a significant challenge • 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 R126 M112 S122 L108 AbbVie Sell-Side
Slide 27: Discovery breakthrough #2
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
Slide 28: Discovery of selective BCL-2 family inhibitor VENCLEXTA
Discovery of selective BCL-2 family inhibitor VENCLEXTA: Breaking new ground in medicinal chemistry F3C O O O– S OH N+ H O N N H S O H O O N S S BCL-2 Protein O O N O NH 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 innovatio
Slide 29: Discovery of MAVYRET: Using structure-based drug design to cure HCV
Discovery of MAVYRET: Using structure-based drug design to cure HCV AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 29
Slide 30: Clinical challenge
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 t
Slide 31: Discovery of MAVYRET
Discovery of MAVYRET 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
Slide 32: Discovery of MAVYRET
Discovery of MAVYRET Based on this model we identified a novel binding pocket AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 32
Slide 33: Discovery of MAVYRET
Discovery of MAVYRET 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 co
Slide 34: Building new capabilities: Computational immuno-oncology
Building new capabilities: Computational immuno-oncology as a basis for target identification and clinical trial design AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 34
Slide 35: Overview of AbbVie's Immuno-oncology (I-O) program
Overview of AbbVie’s Immuno-oncology (I-O) program 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 Recepto
Slide 36: AbbVie I-O programs leverage existing and new capabilities
AbbVie I-O programs leverage existing and new capabilities Oncology I-O Immunology Protein Small Molecule Computational Rational Emerging New Engineering Therapeutics Biology Combinations Biology Technologies AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 36
Slide 37: Computational I-O
Computational I-O 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 S
Slide 38: Computational I-O methods rely on genetic and genomic datasets
Computational I-O methods rely on genetic and genomic datasets obtained from tumor biopsies Example: ICR gene signature CXCR3/CCR5 Chemokines regulatory functions signaling Immune Effector Th1 TCGA- BRCA CXCL9 IFNG GNLY CD274 CXCL10 TBX21 PRF1 CTLA4 CCL5 CD8 GZMA FOXP3 IL12B GZMB IDO1 CD8 GZMH PDCD1
Slide 39: Using tumor-based computational analyses to define next-generation I-O targets
Using tumor-based computational analyses to define next-generation I-O targets and clinical studies 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
Slide 40: Effects of TGF-β on the immune response in cancer
Effects of TGF-β on the immune response in cancer • 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 fun
Slide 41: Application of computational immunology to ABBV-151
Application of computational immunology to ABBV-151 (MOA: GARP/TGF-β) • 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
Slide 42: Tumor inflammation versus TGF-β signaling in bladder urothelial carcinoma
Tumor inflammation versus TGF-β signaling in bladder urothelial carcinoma Immune Presence TGF-β Signaling More likely to respond to PD1 treatment Less likely to respond to PD1 treatment AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 42
Slide 43: New capabilities: Genetics and genomics; innovation in clinical trials
New capabilities: 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 AbbVie Sell-Side R&D Deep Dive | Marc
Slide 44: Genetics and genomics
Genetics and genomics Howard Jacob, Ph.D., Vice President and Head of the Genomics Research Center AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 44
Slide 45: Why is the rate of attrition across pharma pipelines constant?
Why is the rate of attrition across pharma pipelines constant? Target Lead Stage: Discovery Discovery Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Registration Launch • In medicine, knowledge % Success 63% 61% 64% 57% 56% 44% 60% 83% is estimated to be Overall doubling every 18 1.8% months
Slide 46: Building a genomics capability at AbbVie
Building a genomics capability at AbbVie 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 $10
Slide 47: Building a genomics capability at AbbVie
Building a genomics capability at AbbVie Oncology Stratify Patients Immunology Target ID and Confirmation Population cohorts for new indications, New Indications, TNF example target ID and confirmation AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 47
Slide 48: Using human genetics to select gene targets in silico
Using human genetics to select gene targets in silico Using >500,000 genomes to evaluate large numbers of targets in silico Increase accuracy and reduce time to identify AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 48
Slide 49: Functional genomics: Ongoing projects
Functional genomics: Ongoing projects 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 ap
Slide 50: Innovation projects and new initiatives
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
Slide 51: Convergence: Disrupting the discovery and development paradigm
Convergence: Disrupting the discovery and development paradigm Right biology Right target Right molecule Right dose Right patients Target Target Lead Lead Preclinical Pivotal Phase I and II Discovery Validation Generation Optimization Development Trials Leverage doubling of knowledge and manage know
Slide 52: What does this innovation mean for AbbVie?
What does this innovation mean for AbbVie? • 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 • Red
Slide 53: The Development Design Center: Shaping the future of clinical research
The Development Design Center: Shaping the future of clinical research Kyle Holen, M.D., Head, Development Design Center AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 53
Slide 54: The Development Design Center (DDC)
The Development Design Center (DDC): Tailored expertise, predictive analytics and machine learning to deliver efficient trial decisions Growing AbbVie’s growing pipeline demands efficiency and Pipeline innovation Drive The entire portfolio must have access to innovative tools and Consistency cross-t
Slide 55: The DDC approach
The DDC approach 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 AbbVie Sell-Si
Slide 56: DDC goal: Make the smartest decisions
DDC goal: Make the smartest 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-
Slide 57: Using machine learning to accelerate clinical trials
Using machine learning to accelerate clinical trials 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 can predict patient placebo • W
Slide 58: Programs dramatically accelerated by use of machine learning
Programs dramatically accelerated by use of machine learning 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 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020
Slide 59: The DDC in action: ABBV-621 protocol
The DDC in action: Finding patients and designing ABBV-621 protocol • 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 AbbV
Slide 60: What's on the Horizon: 2020 and beyond
What’s on the horizon: 2020 and beyond What’s on the Horizon 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) Forecasting and trial Gathering the building The firs
Slide 61: Expansion of the pipeline
Expansion of the pipeline Expansion of the pipeline Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 61
Slide 62: AbbVie R&D Pipeline - 2020
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):
Slide 63: AbbVie's early target and preclinical portfolio snapshot
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 ●●●●●●●● ●●●●●●●● ●●●●●●●● ●●●●●●●●● ●●●●● ●●● ●●
Slide 64: Our early pipeline will yield approximately 30 POC readouts
Our early pipeline will yield approximately 30 POC readouts in the near-term 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 Immunolog
Slide 65: Oncology
Oncology Neil Gallagher, M.D., Ph.D., Chief Medical Officer and Vice President of Development Oncology AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 65
Slide 66: Despite recent advances, unmet need exists for all tumor types
Despite recent advances, unmet need and opportunity exists for all tumor types 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
Slide 67: AbbVie oncology
AbbVie oncology 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 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 67
Slide 68: Oncology key areas of biology
Oncology key areas of biology 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
Slide 69: We have a compelling oncology pipeline
We have a compelling oncology pipeline Preclinical Phase 1 / Phase 2 Phase 3 / Registrational Submitted / Launched ■ ABBV-467 ■ ABBV-744 ■ VENCLEXTA (1L CLL, 1L AML, ■ VENCLEXTA (1L CLL US) ■ TNB-383B AML maintenance, R/R MM ■ IMBRUVICA + Gazyva (1L tumors Heme t(11;14), MDS) ■ CLBR001/SWI019 CLL US
Slide 70: Transform the treatment of myelofibrosis with Navitoclax
Our goal is to transform the treatment of myelofibrosis with our BCL-XL inhibitor Navitoclax 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, we
Slide 71: Navitoclax + ruxolitinib is a rational combination in myelofibrosis
Navitoclax + ruxolitinib is a rational and potentially transformative combination in myelofibrosis therapy • JAK/STAT activating mutations drive Driving proliferation and an anti-apoptotic effect lesion via MCL-1 up-regulation JAK2 ruxolitinib V617F • JAK2 inhibitor ruxolitinib (Jakafi) + reduces JA
Slide 72: BCL-XL inhibition overcomes resistance to JAK2 inhibitors
BCL-XL inhibition overcomes resistance to JAK2 inhibitors 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 Cel
Slide 73: Navitoclax overcomes ruxolitinib resistance
Navitoclax overcomes ruxolitinib resistance resulting in splenomegaly improvement for most patients • 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 bon
Slide 74: Building an industry-leading portfolio in apoptosis
Building an industry-leading portfolio in apoptosis and regulated cell death 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-
Slide 75: Leveraging BCL-XL inhibition to treat solid tumors requires tumor targeting
Leveraging BCL-XL inhibition to treat solid tumors requires tumor targeting 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 clinica
Slide 76: ABBV-621: TRAIL demonstrating monotherapy activity
ABBV-621: TRAIL demonstrating monotherapy activity • Novel TRAIL agonist with a pair of trimerized Subject with KRASMT CRC with confirmed PR, sustained for 200+ receptor binding domains that optimize clustering days after 3 prior lines of therapy of TRAIL receptors independent of Fc engagement, best
Slide 77: ABBV-467: Important apoptotic pathway in solid and heme tumors
ABBV-467: Important apoptotic pathway in solid and heme tumors Preclinical Systemic AML Model (MV4;11) • MCL-1 is widely expressed in heme 1.E+12 Tumor load (#p*s-1) vehicle ABT-199 50 mg/kg, QDx21 vehicle and solid tumors; allows cancer cells 1.E+11 to evade apoptosis 1.E+10 A-1726694 12.5 mg/kg, Q
Slide 78: Tumor-specific antigen targeting and next milestones
Summary of key opportunities in tumor-specific antigen targeting and next milestones 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
Slide 79: Leverage strengths in ADCs and novel target identification
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, gastroesophagea
Slide 80: We have a growing I-O pipeline
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 Sol
Slide 81: ABBV-151 is a novel approach to disrupt the tumor microenvironment
ABBV-151 is a novel approach to disrupt the tumor microenvironment • 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 •
Slide 82: T-cell redirection: Building a world-class CD3 portfolio
T-cell redirection: Building a world-class CD3 portfolio 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
Slide 83: Our immune cell redirection platform interrogates multiple variables
Our immune cell redirection platform interrogates multiple variables 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
Slide 84: We have a compelling oncology pipeline
We have a compelling oncology pipeline Preclinical Phase 1 / Phase 2 Phase 3 / Registrational Submitted / Launched ■ ABBV-467 ■ ABBV-744 ■ VENCLEXTA (1L CLL, 1L AML, ■ VENCLEXTA (1L CLL US) ■ TNB-383B AML maintenance, R/R MM ■ IMBRUVICA + Gazyva (1L tumors Heme t(11;14), MDS) ■ CLBR001/SWI019 CLL US
Slide 85: Immunology
Immunology Lisa Olson, Ph.D., Vice President Immunology Discovery Immunology AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 85
Slide 86: Leader in the field of immunology
Leader in the field of immunology, pursuing breakthrough science and delivering best-in-class medicines 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 stan
Slide 87: Eliminate the burden for all those touched by immune-mediated diseases
Eliminate the burden for all those touched by immune-mediated diseases by advancing an industry-leading portfolio of transformational agents Clinical goals: Scientific goals: Rheumatology: Rheumatoid arthritis and lupus • Molecular understanding of disease pathology • Identification of new pathways
Slide 88: Utilization of the ADC technology for immune-mediated diseases
Utilization of the ADC technology for immune- mediated diseases Payload Linker required improvements 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
Slide 89: Why combine anti-TNF and steroid into an ADC?
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 HO • They are often used in combination OH H but the use of steroids is limited
Slide 90: Why combine anti-TNF and steroid into an ADC?
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 • They are often used in combination O OH but the use of steroids is limited to Arthritic
Slide 91: Anti-TNF-steroid ADC demonstrates targeted uptake and release
Anti-TNF-steroid ADC demonstrates targeted uptake, internalization and internal release of steroid in activated immune cells Hypothesis: Targeting activated immune cells with the anti-TNF-steroid ADC will demonstrate durable inhibition of inflammation with no steroid side effects Targeted steroid re
Slide 92: Repeat dosing of the TNF ADC reverses inflammation in mouse arthritis model
Repeat dosing of the TNF ADC reverses inflammation, maintains remission and restores bone to naïve levels in a mouse model of arthritis 1 .0 V e h ic le C h a n g e in P a w T h ic k n e s s ( m m ) A n ti- T N F - s t e r o id A D C 0 .8 0 .6 0 .4 Naive Day 7 Baseline * * 0 .2 * * * * * * * * * *
Slide 93: Systemic glucocorticoid safety translated from preclinical species to humans
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
Slide 94: Advancing ABBV-3373 to clinical studies
Advancing ABBV-3373 to clinical studies: Our goal is to achieve transformational efficacy in three disease areas, starting with RA Rheumatology Dermatology Gastroenterology RA, PsA & Others Hidradenitis suppurativa Crohn’s disease | Ulcerative colitis Achieve durable remission and Achieve full skin
Slide 95: Next generation iADC platform strategy
Anchored by the success of the anti-TNF-steroid ADC, the next generation Myeloid Cell Targeting Monocyte Dendritic Cells pDC Macrophage iADC platform Lymphocyte Targeting strategy involves T-cells B Cells Targeting only Cells within the Inflamed Tissue more selectively Dendritic cells targeting path
Slide 96: ABBV-599 (combination of ABBV-105 and upadacitinib)
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
Slide 97: ABBV-599: JAK1/BTK in Phase 2 in RA
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 s
Slide 98: The challenge of understanding and driving remission in IBD
The challenge of understanding and driving remission in IBD AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020
Slide 99: The best available IBD therapies leave significant room for improvement
The best available IBD therapies leave significant room for improvement 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
Slide 100: Immune cell modulation and healing of the epithelial barrier in IBD
Our hypothesis: For transformational efficacy in IBD, both immune cell modulation and healing of the epithelial barrier are required Compromised barrier function, aberrant responses to bacteria Lumen Therapeutic approach: MOAs that drive mucosal healing Mucous Microbes Epithelium Mucus IL-22 IEL Inc
Slide 101: EP4 agonism will reduce inflammation and improve mucosal healing
EP4 agonism will reduce inflammation and improve mucosal healing • 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 100 80 Control % c o n tr o l 60
Slide 102: EP4 agonism protects the mucosa in murine models of colitis
EP4 agonism reduces inflammation and protects the mucosa in murine models of colitis Anti-inflammatory Mucosal Healing Injection of Takedown anti-CD40 agonist Day 0 Day 6 Day 7 MUC2-zsGreen Start DSS CLE scoping Takedown Day -1 Day 0 Day 2 Day 7 mice EP4 PO BID αTNFa IP αTNFa IP 3% DSS Body weights
Slide 103: Summary
Summary • 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 e
Slide 104: Neuroscience
Neuroscience Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer Neuroscience AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 104
Slide 105: Why AbbVie is investing in neurodegenerative diseases
Why AbbVie is investing in neurodegenerative diseases 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 AbbVie Sell-Side R&D Deep Dive | Marc
Slide 106: Our neuroscience pipeline is targeted to areas of continued unmet need
Our neuroscience pipeline is targeted to areas of continued unmet need 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 Lon
Slide 107: Need for a non-surgical treatment option for advanced Parkinson's disease
There is a need for an effective, non-surgical treatment option for advanced Parkinson’s disease patients 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,
Slide 108: Continuous subcutaneous infusion of levodopa and carbidopa
Our aspiration was to develop a way to provide continuous subcutaneous infusion of levodopa and carbidopa 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 adm
Slide 109: ABBV-951 development program timeline
ABBV-951 development program timeline: Program progressed directly from Phase 1 to Phase 3 2018 2019 2020 2021 2022 2023 Commercial Drug Delivery System Development Ph1 SAD Ph1b Pivotal Study #1 Pivotal Study #2 Pivotal Study #3 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 109
Slide 110: Protein aggregates spread through the brain in neurodegenerative diseases
In many neurodegenerative diseases, protein aggregates form and spread through the brain from neuron to neuron, causing neuronal loss Intra-cellular protein misfolding and aggregation Propagation correlates with neuronal loss and functional decline Functional proteins One abnormal Abnormal protein E
Slide 111: AbbVie's neuroscience pipeline
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
Slide 112: Alector collaboration testing antibodies to neuroinflammation targets
Alector collaboration testing antibodies to compelling neuroinflammation targets 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 • Activatio
Slide 113: Cystic fibrosis
Cystic fibrosis 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
Slide 114: Cystic fibrosis: Rationale and status
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 • 20% of patients have an FEV1 improvement of 5% or less ABBV-
Slide 115: Calico
Calico Tom Hudson, M.D., Senior Vice President, R&D and Chief Scientific Officer Calico AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 115
Slide 116: Calico and the AbbVie-Calico collaboration
Calico and the AbbVie-Calico collaboration • 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
Slide 117: State of the collaboration
State of the collaboration 13 YEARS 400+ SCIENTISTS CLINICIANS 44+ TARGETS 2 PROJECTS Collaboration RUNWAY At ABBVIE and CALICO In the Joint PORTFOLIO In CLINICAL TRIALS by 2020 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 117
Slide 118: Collaboration metrics
Collaboration metrics The portfolio is split between oncology and neurodegeneration Current 26 Jan 2020 AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 118
Slide 119: Calico portfolio snapshot (January 2020)
Portfolio snapshot (January 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 • Clini
Slide 120: AbbVie's discovery portfolio and pipeline snapshot
AbbVie’s discovery Evolution of AbbVie R&D portfolio and pipeline snapshot Mike Severino, M.D., Vice Chairman and President AbbVie Sell-Side R&D Deep Dive | March 10, 2020 | © 2020 120
Slide 121: AbbVie's discovery portfolio and clinical pipeline
AbbVie’s discovery portfolio and clinical pipeline As of February 7, 2020 Early Target Portfolio Late Discovery Portfolio Clinical Development Therapeutic Candidate Area Lead Exploratory Hit Generation Lead Optimization Nomination Pre-Clinical Phase 1 Phase 2 Phase 3 Generation & Selection Immunolog
Slide 122: aQobvie
aQobvie