Gsk Plc · LSE:GSK
Gsk — Investor Day (November 2015)
137 slides from Gsk's investor day presentation, Nov 3, 2015
Slide 1: Innovative Pipeline
Innovative Pipeline Sir Andrew Witty 3 November 2015
Slide 2: Cautionary statement regarding forward-looking statements
Cautionary statement regarding forward-looking statements This presentation contains forward-looking statements. Forward-looking statements give the Group’s current expectations or forecasts of future events. An investor can identify these statements by the fact that they do not relate strictly to h
Slide 3: Innovation is critical to maximising the potential of GSK
Innovation is critical to maximising the potential of GSK in the current environment Pharmaceuticals Vaccines Consumer Future R&D Broad portfolio innovation offering Global footprint + regulatory and quality competence Clear >6 billion But pricing >7 billion people volume people 650m ~1 billion 60+
Slide 4: R&D Strategy: Reliable fill & flow with greater novelty and improved return on investment
R&D Strategy: Reliable fill & flow with greater novelty and improved return on investment Accelerate Focus where science Improve balance Reduce Acute fixed cost Discovery output is innovative internal vs external complicated and improve ROI infectious diseases • Now have 30 DPUs, of which • Of the ~
Slide 5: New product launches and generics exposure
New product contribution increasing as generic exposure reduces 2021 - 2025 2015 - 2020 11 new products* with at least £6bn ~ 30 Phase II NME/PLE starts in 2008 - 2014 expected sales, with 9 marketed 2016/17 Launches 28 first approvals of new products generating £1.3 billion in ~ 20 Phase III NME/PL
Slide 6: New product growth more than offsets Advair decline
New product growth more than offsets Advair decline Q115 Q1 Q2Q2 15 Q315 Q3 £412m New product growth*^ £321m £221m Seretide/Advair decline^ £141m £135m £182m * New products defined as: Rx: Breo, Anoro, Incruse, Arnuity, Tanzeum, Tivicay, Triumeq. Vx: Menveo, Bexsero ^ Growth and decline in the respe
Slide 7: Assets profiled at R&D day by planned filing date
Assets profiled at R&D day by planned filing date 2014 2018 2021 to to to 2017 2020 2025 7 NMEs & 5 PLEs 11 NMEs & 5 PLEs 21 NMEs & 5 PLEs Nucala sirukumab mepolizumab tarextumab† GSK2398852+ sirukumab GSK3008348 GSK525762 GSK3196165 RSV paediatric (mepolizumab) IL-6 mAb IL-5 mAb Notch 2/3 mAb GSK23
Slide 8: Focus on delivering innovative and sustainable presence in key areas
Focus on delivering innovative and sustainable presence in 6 key areas HIV / Infectious Respiratory Vaccines Diseases Immuno– Oncology Rare Inflammation Diseases 8
Slide 9: Focus for today: Innovation to deliver products of value
Focus for today: Innovation to deliver products of value Patrick Vallance Moncef Slaoui President, Pharmaceuticals R&D Chairman of Vaccines 9
Slide 10: Patrick Vallance
Patrick Vallance President, Pharmaceuticals R&D
Slide 11: GSK R&D: what is important to us
GSK R&D: what is important to us Innovative Patient Quality science need • Average of 35 publications annually in • 5 Breakthrough Designations since 2013 GSK achieved highest number of FDA worlds-class journals (Nature, Cell, approvals, 2010-15 14 • 3 FDA Priority Reviews since 2010 GlaxoSmithKline
Slide 12: Recruiting and developing the best scientists
Recruiting and developing the best scientists We’re committed to ensuring GSK remains the best place to develop medicines World-class External talent Scientific Expert leaders sourcing career advisory pathways networks Academia Industry Biotech 12
Slide 13: HIV / Infectious Diseases
HIV / Infectious Diseases
Slide 14: Infectious disease burden continues to grow and present public health challenges
Infectious disease burden continues to grow and present public health challenges HIV HBV HCV Acute complicated infectious diseases • 36.9m living with HIV • Globally, 240m people • Globally, 130-150m • Globally, ~3.5m annual worldwide; 1.2m deaths & have Chronic Hepatitis B1 people have Chronic deat
Slide 15: Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure
Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure HIV Innovative Long-acting Treatment Treatment GSK Pipeline Regimens HCV/HBV Prevention Remission & Cure Acute complicated infectious disease 15
Slide 16: Dolutegravir set to be at the heart of future treatment regimens
Dolutegravir set to be at the heart of future treatment regimens Dolutegravir profile Efficacy DTG/3TC: Planned launch H1 2019 • Rapid and sustained viral load drop 2-drug STR for HIV treatment in naïve and suppressed patients, QD Simplification - Potential benefit on tolerability and drug burden Ba
Slide 17: PADDLE: Investigator sponsored study design
PADDLE (Pilot Antiretroviral Design with Dolutegravir and LamivudinE): Investigator sponsored study design • Investigator sponsored study Patient # Base line viral load Week 8 Week 24 1 10.909 < 50 < 50 • 2 tablet treatment 2 3 10.233 151.569 < 50 < 50 < 50 < 50 4 148.370 < 50 < 50 • ARV naive patie
Slide 18: Cabotegravir: Long-acting antiretroviral
Cabotegravir: Long-acting antiretroviral Long-acting HIV Treatment HIV Prevention Mean concentration/time profile following single injection1 LATTE Week 96 Results2 100mg IM 100mg SC Pre-clinical data 200mg IM 200mg SC 100 400mg IM 400mg SC (split) 800mg IM (split) 8/8 protected 80 cabotegravir LA P
Slide 19: Cabotegravir long-acting clinical studies
Cabotegravir long-acting clinical studies Potential for better adherence 4Q2015 LATTE 2 results HIV TREATMENT Key Phase III-enabling data: combination CAB LA + RPV LA CAB LA + RPV LA as maintenance therapy (ViiV Healthcare - Janssen sponsored) Planned launch: Mid-2016 HIV Treatment Phase III start 2
Slide 20: LATTE 2 - cabotegravir LA + rilpivirine LA for treatment of HIV
LATTE 2 - cabotegravir LA + rilpivirine LA for treatment of HIV Headline data – path to Phase III • Phase IIb trial examining long-acting (LA) cabotegravir (CAB) in combination with LA rilpivirine (RPV). 309 treatment naïve subjects initially treated with QD oral CAB 30mg + 2 NRTIs • Following virol
Slide 21: Next wave cabotegravir long-acting combinations
Next wave cabotegravir long-acting combinations Opportunities with broadly neutralising antibodies • Cabotegravir long-acting • Broadly neutralising antibodies (bnAbs) • Every 2 or 3 months • GSK and the National Institute of Allergy and Infectious Diseases/National Institutes of Health Nano-formula
Slide 22: GSK & Regulus combination for single administration HCV treatment
GSK & Regulus combination offers potential for a single administration treatment for HCV Single dose RG-101 • RG101 lowers viral load Prolonged VL declines in HCV patients Log10 reduction of HCV • GSK2878175 lowers viral viral load decline -1 RG-101 2 mg/kg n=14 load RG-101 4 mg/kg n=14 n=4 placebo
Slide 23: GSK & Isis collaboration targeting HBV functional cure
GSK & Isis collaboration targeting next generation of HBV medicines: functional cure • Antisense approach taken Reduction of HBV antigen by anti-HBV ASO in mice to knock down immune suppressive antigens Serum HBV Surface Antigen Serum HBV e Antigen Serum HBeAg (% before treatment) Serum HBsAg (% bef
Slide 24: Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure
Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure HIV Innovative Long-acting Treatment Treatment GSK Pipeline Regimens HCV/HBV Prevention Remission & Cure Acute complicated infectious disease 24
Slide 25: First in a new class of antibacterials: gepotidacin
First in a new class of antibacterials: gepotidacin (GSK2140944) – a topoisomerase inhibitor • Novel mechanism with bactericidal 100 activity against MDR pathogens Percent survival 80 All gepotidacin treated survived • Promising safety & efficacy profiles 60 (all organs culture negative) in Phase II
Slide 26: Infectious Diseases strategy: from innovative regimens to treatment and the pursuit of cure
Infectious Diseases strategy: from innovative regimens to treatment and the pursuit of cure − dolutegravir based regimens − cabotegravir LA − cabotegravir LA + rilpivirine LA − Next generation agents and combinations Innovative Long-acting Treatment Treatment GSK Pipeline Regimens − HCV − HBV HIV, H
Slide 27: Respiratory
Respiratory
Slide 28: Respiratory diseases: still significant unmet need
Respiratory diseases: still significant unmet need Asthma COPD Lung Fibrosis & Acute Lung Injury • Globally 242m people have • 329m people worldwide have • Each affects ~5m patients asthma (32% increase since 1990) COPD worldwide • Gold-standard options delivered • 3rd leading cause of death by • Id
Slide 29: Asthma R&D strategy: from secondary prevention to primary disease modification
Asthma R&D strategy: from secondary prevention to primary disease modification eosinophil Targeted Biologicals Extended Duration Biologicals GSK Pipeline neutrophil Once Daily Inhaled Remission-inducing dendritic cell 29
Slide 30: Nucala (mepolizumab) demonstrates significant reduction in exacerbations
Nucala™* (mepolizumab) demonstrates significant reduction in exacerbations Nucala (subcutaneous anti-IL-5 mAb): mepolizumab (s.c. or i.v.) reduced the number of asthma exacerbations in patients with severe eosinophilic • Straightforward patient selection & asthma biomarker 250 • 53% reduction in exa
Slide 31: Nucala will be first in class with a strong profile
Nucala will be first in class with a strong profile XOLAIR dupilumab reslizumab benralizumab lebrikizumab tralokinumab Nucala Novartis/ Sanofi/ Teva AstraZeneca Roche AstraZeneca Genentech Regeneron Phase Submitted Launched Submitted Ph III ongoing Ph III ongoing Ph III ongoing Ph III ongoing Earlie
Slide 32: Nucala has potential in other indications
Nucala* has potential in other indications Anticipated file timelines 2014 to 2016 2017 2018 2019 2020+ 2015 Asthma – Evidence Generation COPD – Evidence Generation Eosinophilic granulomatosis with polyangiitis (EGPA) Hyper-eosinophilic syndrome (HES) Nasal polyposis / Chronic rhinosinusitis Atopic
Slide 33: Two novel biologicals
Two novel biologicals Targeted approaches for uncontrolled asthma patients sirukumab* (IL-6 mAb): Non-Th2 asthma TSLP dAb: Inhaled biologic • Targets severe disease ineligible for Th2/eosinophilic directed mAbs • Thymic Stromal Lymphopoietin (TSLP): key cytokine in (40% of severe asthma patients) ep
Slide 34: Nucala is at forefront of a diverse asthma biologic pipeline
Nucala is at forefront of a diverse asthma biologic pipeline Nucala sirukumab Long acting Anti-TSLP dAb Anti-IL-5/13 Anti-IL-5 Anti-IL-6 Anti-IL-5 (NBE) Bispecific dAb-mAb Modality mAb mAb Extended pharmacology mAb Inhaled dAb in Ellipta extended pharmacology Delivery SC SC SC Inhaled SC mechanism E
Slide 35: GSK2245035 intranasal TLR7 agonist
GSK2245035 intranasal TLR7 agonist Demonstrates prolonged suppression of allergic response • Activates immune pathways that suppress Weekly dosing with intranasal GSK2245035 for 8 weeks exaggerated Th2 response in asthma in allergic rhinitis patients • Allergen-independent immune modulation Mean IP
Slide 36: Asthma R&D strategy: From secondary prevention to primary disease modification
Asthma R&D strategy: From secondary prevention to primary disease modification Targeted Biologicals Extended Duration Biologicals • Nucala • sirukumab GSK Pipeline • Long-acting anti-IL-5 • Anti-TSLP dAb • Anti-IL-5/13 • Anti-IL-5/13 Once Daily Inhaled Remission-inducing • Relvar/Breo Ellipta™ • TLR
Slide 37: COPD R&D strategy: Targeting the fundamental drivers of disease
COPD R&D strategy: Targeting the fundamental drivers of disease eosinophil Targeted Biologicals Infection Driven Exacerbations GSK Pipeline neutrophil Once Daily Inhaled Preserve Lung Function epithelial cell 37
Slide 38: Closed Triple: once daily triple therapy in established Ellipta inhaler
Closed Triple: once daily triple therapy in established Ellipta inhaler • Collaboration with Theravance Consistent improvement in lung function with UMEC plus • Open triple filed with FDA ICS/LABA vs. ICS/LABA • Phase IIIa lung function study fully recruited (FULFIL) UMEC add on vs. ICS/LABA (Study
Slide 39: GSK2269557, inhaled PI3Kδ inhibitor targets neutrophil-mediated lung damage in COPD
GSK2269557, inhaled PI3Kδ inhibitor targets neutrophil- mediated lung damage in COPD • PI3Kδ over-activation causes human rare disease Activating mutations in PI3Kδ in APDS drive lung infections activated PI3Kδ syndrome (APDS) • APDS patients display severe recurrent COPD-like bacterial infections •
Slide 40: Danirixin: an oral CXCR2 antagonist
Danirixin (GSK1325756): an oral CXCR2 antagonist Demonstrates potential to reduce lung damage in COPD • Blocks chemokine receptor on neutrophils and other cell types (CXCR2) Real-time data demonstrate improvement of symptoms with danirixin in symptomatic COPD (frequent exacerbators) • Target engagem
Slide 41: COPD R&D strategy: pipeline
COPD R&D strategy: pipeline Targeting the fundamental drivers of disease Targeted Biologicals Infection Driven Exacerbations • Nucala • PI3Kδ • danirixin GSK Pipeline Once Daily Inhaled Preserve Lung Function • Anoro™ Ellipta • PI3Kδ • Relvar/Breo Ellipta • danirixin • Incruse Ellipta • Closed Tripl
Slide 42: Drivers of our long-term leadership in asthma and COPD
Drivers of our long-term leadership in asthma and COPD • Excellence in inhaler / delivery technologies neutrophil eosinophil • Targeted biological know-how • Deep understanding of novel respiratory targets • Understanding of patient phenotypes • Expertise in trial design and delivery epithelial cell
Slide 43: Respiratory R&D beyond Asthma and COPD
Respiratory R&D beyond Asthma and COPD Taking our respiratory know-how into new diseases Platform for clinical development of IPF (GSK3008348) vβ6 PET ligand binds to fibrotic regions in IPF lungs • αvβ6 expression in IPF lung biopsies predicts mortality • Small molecule inhaled αvb6 inhibitor (dep
Slide 44: PHI and Oxygen Sensing
PHI and Oxygen Sensing
Slide 45: Daprodustat low dose PHI for treatment of anaemia of CKD
Daprodustat1 (GSK1278863) low dose PHI for treatment of anaemia of CKD: New Phase IIb data • Standard of care (rhEPO) limited by increased CV risk and IV/SQ administration daprodustat Phase IIb3: • PHI oral tablet to replace injectable rhEPO: low dose, Pre-dialysis subjects naive to rhEPO; target Hg
Slide 46: Daprodustat: success factors for development
Daprodustat: success factors for development Key success factors • Low dose Large experience in CKD subjects 659 (up to 6 months) • No inhibition of collagen- 4-hydroxylase Active comparator for CV safety assessment Yes (rhEPO) • Single Phase III CV Low dose 10mg QD in most outcomes studies for su
Slide 47: Daprodustat: indication expansion
Daprodustat Indication expansion to maximise value of HIF-activating mechanism Diabetic Foot Ulcer Muscle injury from repetitive arm motion in healthy volunteers – Preclinical data demonstrate benefit of HIF induction in diabetic skin – Topical daprodustat formulation in ongoing Phase Ib study – No
Slide 48: Introducing our experts
Introducing our experts GSK’s leading scientists in infectious disease, respiratory medicine and CV Zhi Hong John Pottage Senior Vice President, Senior Vice President, Head Infectious Diseases Chief Scientific and Medical TAU Officer for ViiV Healthcare Dave Allen Edith Hessel Steve Pascoe Senior Vi
Slide 49: Q&A
Q&A
Slide 50: Moncef Slaoui
Moncef Slaoui Chairman of Vaccines
Slide 51: R&D programmes to deliver near-term growth and novel immunisation platforms
R&D programmes to deliver near-term growth with significant future opportunities and novel immunisation platforms 3 A new vaccine concept − COPD Longer term R&D Focus 2 − RSV − GBS Near/mid term key R&D focus: − ShingrixTM 1 − Meningitis − Lifecycle management RSV=Respiratory Syncytial Virus; GBS=Gr
Slide 52: Shingrix
ShingrixTM Shingrix™ is not approved for use by the FDA or EMA
Slide 53: Existing zoster vaccine
Existing zoster vaccine One dose, live attenuated vaccine Efficacy: 51% against shingles in ages 60+ – Inverse correlation between age at vaccination and protection – Limited persistence of protection Indication for ages 50+ US ACIP recommendation for ages 60+ Contraindicated in immunocompromised in
Slide 54: Shingrix candidate vaccine developed to differentiate
Shingrix candidate vaccine developed to differentiate Two doses, sub-unit (non-live) vaccine, novel adjuvant Efficacy: 91% - 97% against shingles – High efficacy across identified age groups – Persistence over time Targeting indication and recommendation in ages 50+ Data on immunocompromised individ
Slide 55: Shingrix - Efficacy against shingles
Shingrix - Efficacy against shingles 100 90 80 Efficacy against shingles - % 70 60 50 40 30 20 10 0 50-59 yrs 60-69 yrs 70+ yrs Lal et al. N Engl J Med 2015; ZOE-50 and ZOE-70 pooled analysis – unpublished data Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head
Slide 56: Existing vaccine - Efficacy against shingles
Existing vaccine - Efficacy against shingles 100 90 Efficacy against shingles - % 80 70 60 50 40 30 20 10 0 50-59 yrs 60-69 yrs 70+ yrs Oxman et al. N Engl J Med 2005; 352: 2271–84; Schmader et al. Clinical Infectious Diseases 2012;54(7):922–8; Zostavax™ US PI 56 Not based on head to head data; Shin
Slide 57: Shingrix - Immune response across age segments
Shingrix - Immune response across age segments Frequency of gE-specific CD4+ T cells by age groups Number of CD4+ T cells per million 3500 3000 2500 2000 1500 1000 500 0 50-59 50-59yrs 60-69 yrs 60-69 70-79 yrs 70-79 ≥ 80 yrs ≥ 80 saline gE/saline gE/AS01B Chlibek et al. J Infect Dis 2013; 208:1953-
Slide 58: Existing vaccine - Immune response across age segments
Existing vaccine - Immune response across age segments vaccine placebo Responder cell frequency value 12 9 6 3 0 N=V/P 204/240 186/188 162/149 103/94 31/31 60-64 yrs 65-69 yrs 70-74 yrs 75-79 yrs >79 yrs Levin et al. J Infect Dis 2008; 197:825–35 Not based on head to head data; Shingrix™ and Zostava
Slide 59: Shingrix - Efficacy against PHN
Shingrix - Efficacy against PHN PHN: post herpetic neuralgia, a severe complication of zoster 100 90 80 Efficacy against PHN - % 70 60 50 40 30 20 10 0 Over 50 yrs Over 60 yrs Over 70 yrs ZOE-50 and ZOE-70 pooled analysis – unpublished data Not based on head to head data; Shingrix™ and Zostavax™ hav
Slide 60: Existing vaccine - Efficacy against PHN
Existing vaccine - Efficacy against PHN PHN: post herpetic neuralgia, a severe complication of zoster 100 90 80 Efficacy against PHN - % 70 60 50 40 30 20 10 0 50-59 yrs 60-69 yrs 70+ yrs Zostavax US PI; Oxman et al. N Engl J Med 2005 Not based on head to head data; Shingrix™ and Zostavax™ have not
Slide 61: Shingrix - Duration of protection against shingles
Shingrix - Duration of protection against shingles 100 Efficacy against shingles - % 80 60 40 20 0 Yr1 Yr2 Yr3 Yr4 Yr5 Yr6 ZOE-50 statistical report – unpublished data Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Shingrix data based on ph III clinical tr
Slide 62: Existing vaccine - Duration of protection against shingles
Existing vaccine - Duration of protection against shingles 100 Efficacy against shingles - % 80 60 40 20 0 Yr1 Yr2 Yr3 Yr4 Yr5 Yr6 Morrison et al. Clin Infect Dis 2015; 60: 900-909 Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Zostavax data based on publi
Slide 63: Immune response persistency is a good predictor of duration of efficacy
Immune response persistency is a good predictor of duration of efficacy Shingrix immune response 10000 gE-specific CD4+ T-cells / million cells (geometric mean frequency (GMF) 1000 100 10 0 1 2 3 4 5 6 Years of follow up Chlibek et al. Vaccine 2015 doi:10.1016/j.vaccine.2015.09.073 63 Not based on h
Slide 64: Shingrix: a potentially significant advance in vaccination to prevent shingles
Shingrix: a potentially significant advance in vaccination to prevent shingles High overall vaccine efficacy across identified age groups, including oldest 2016 2017 2018 2019 persons Persistence of vaccine efficacy up to 4 years across all ages H2: US, EU, Japan Filings Six-year persistence of immu
Slide 65: Meningococcal Meningitis
Meningococcal Meningitis
Slide 66: Meningococcal disease: evolving and unpredictable epidemiology
Meningococcal disease: evolving and unpredictable epidemiology – requires combination vaccine ~139 million annual global birth cohort 1 Disease incidence by age (2012) 1 ~4m US, ~5m EU, ~130m ROW US3 0.8 0.6 Changes in serogroup distribution in US over time2 Number of cases per 100,000 0.4 0.2 0 <5
Slide 67: Most advanced meningitis vaccines portfolio, including candidate pentavalent
Most advanced meningitis vaccines portfolio, including candidate pentavalent MenveoTM BexseroTM MenABCWY – MenACWY tetravalent vaccine – MenB vaccine – Candidate pentavalent combination vaccine for – Approved in US and EU (2010) – Approved in US in 2015 adolescent in US (adolescents) and EU (2 month
Slide 68: Bexsero: multi-component antigen composition adds value
Bexsero: multi-component antigen composition adds value, differentiation Bexsero – 4 antigens composition – 2 dose regimen 100 % subjects with bactericidal activity 80 60 40 20 0 Strain 1 Strain 2 Strain 3 Strain 4* Baseline 1m Post Dose 1 1m Post Dose 2 Sources: Santolaya et al. Hum Vac & Imm 2013
Slide 69: Competing vaccine for MenB
Competing vaccine for MenB Competing vaccine – 1 antigen composition with 2 variants – 3 dose regimen % subjects with bactericidal activity 100 80 60 40 20 0 Strain 1 Strain 2 Strain 3 Strain 4 Baseline 1m Post Dose 1 1m Post Dose 2 1m Post Dose 3 ClinTrial.gov, study NCT01299480 https://goo.gl/Eqbm
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Slide 72: MenABCWY Phase III starts in 2017
MenABCWY Phase III starts in 2017 – US focused development 11 years 17 years – 1 dose adolescent booster – Phase III programme start in 2017 MenACWY MenACWY MenACWY (~80% (~29% – Filing expected 2020 for adolescents schedule penetration) penetration) previously immunised for MenACWY Post dose 2 immu
Slide 73: Meningitis portfolio presents significant opportunity
Meningitis portfolio presents significant opportunity GSK has most advanced and comprehensive portfolio for meningitis vaccines Bexsero demonstrated 2017 2018 2019 2020 significant public health benefit, could drive further UMV recommendations Combination approach is MenABCWY Bexsero MenABCWY optima
Slide 74: Respiratory Syncytial Virus (RSV)
Respiratory Syncytial Virus (RSV)
Slide 75: Period of most severe RSV cases for young infants
Period of most severe RSV cases for young infants occurs from birth to 12 months 35,000 30,000 US Hospitalisations 25,000 20,000 15,000 10,000 5,000 0 0-2 3-5 6-8 9-11 12-14 15-17 18-20 21-23 mos mos mos mos mos mos mos mos Paramore, Pharmacoeconomics 22:274-285, 2004 75
Slide 76: Period of most severe RSV cases for young infants
Period of most severe RSV cases for young infants occurs from birth to 12 months 35,000 Maternal Vaccine Paediatric Vaccine 30,000 US Hospitalisations 25,000 Week of pregnancy Age in months 28 30 32 34 36 38 40 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 20,000 Maternal Paediatric 15,000 10,000 Maternal I
Slide 77: Candidate paediatric RSV vaccine, a novel approach
Candidate paediatric RSV vaccine, a novel approach Genetically engineered recombinant CHAd155 Same vector used in ebola vaccine Phase Phase Phase I II – III Non-alum composition Healthy Sero+ infants Sero- infants Sero- infants fibre men 6-18 mos 2-12 mos 2 mos Sero- infants Proof of Study start cor
Slide 78: Novel candidate RSV maternal vaccine approach
Novel candidate RSV maternal vaccine approach Absorbtion with Pre-F but not Site II Post-F depletes neutralising Site IgG from convalescent serum For RSV F protein, the SiteIV Site IV Site Ø Site Ø correct antigen structure 100 % neutralising antibody absorbed Site Site IIII is critical Site IIII Si
Slide 79: Stabilised Pre-F generated high titers and potent boost of PCA
Stabilised Pre-F generated high titers by Day 7 and potent boost of PCA without adjuvant GSK Pre-F 2048 25 Neutralising Ab Titer Fold increase PCA 20 1024 15 512 10 256 5 128 0 60 plain 60 plain Day 30 Day 0 Day 7 Day 30 >20 fold PCA increase after single dose without adjuvant GSK internal data, unp
Slide 80: Stabilised Pre-F generated high titers and potent boost of PCA
Stabilised Pre-F generated high titers by Day 7 and potent boost of PCA without adjuvant GSK Pre-F Post-F 2048 25 2048 25 Neutralising Ab Titer Neutralising Ab Titer Fold increase PCA Fold increase PCA 20 20 1024 1024 15 15 512 512 10 10 256 256 5 5 128 0 128 0 60 plain 60 plain 60 plain 60 Al 120 A
Slide 81: Novel candidate RSV maternal vaccine approach
Novel candidate RSV maternal vaccine approach Phase Phase Phase Phase I IIa IIb III – Healthy men Non-pregnant Pregnant VE in infants of women women vaccinated Dose selection women Proof of Study start principle 2019 2018 Completed Ongoing Planned 81
Slide 82: Group B Streptococcus (GBS)
Group B Streptococcus (GBS)
Slide 83: Maternal immunisation for GBS
Maternal immunisation for GBS The leading No GBS disease GBS disease 40 cause of pneumonia, meningitis and sepsis in 35 neonates 30 % infants 25 1 in 2500 of babies develop GBS disease 20 despite antibiotic 15 prophylaxis of colonised mothers 10 5 No vaccine is available 0 <0.5 <0.5-.99 10-14.99 15-
Slide 84: Maternal immunisation for GBS
Maternal immunisation for GBS The leading No GBS disease GBS disease 40 cause of pneumonia, meningitis and sepsis in 35 neonates 30 % infants 25 1 in 2500 of babies develop GBS disease 20 Protected despite antibiotic 15 prophylaxis of colonised mothers 10 5 No vaccine is available 0 <0.5 <0.5-.99 10
Slide 85: GBS maternal immunisation expanded programme
GBS maternal immunisation expanded programme Large Phase II trivalent completed Based on Capsular polysaccharide (CPS) Decision to expand composition to pentavalent from 5 dominant GBS Validate correlate of protection with FDA serotypes conjugated to Clinical development plan to be agreed with FDA a
Slide 86: Maternal immunisation validated strategy to prevent diseases in young infants
Maternal immunisation validated strategy to prevent diseases that afflict very young infants Infants protected by maternal flu vaccination 0.05 VE = 50.5% p = 0.01 – confirmed influenza – Proportion with Placebo Flu vaccine 0.00 0 2 4 6 Age (months) Source: N Engl J Med. 2014 Sep 4;371(10):918-31 86
Slide 87: GSK potential maternal immunisation vaccine portfolio
GSK potential maternal immunisation vaccine portfolio Pertussis GBS 50% 45% 40% 35% Percent of cases 30% 25% Influenza 20% RSV 15% 10% 5% Influenza-Associated Mortality 0% (deaths per 100,000 children) 0-7d 8-30d 30-90d >90d Age of onset Winter K, MMWR 63:1122- 1140,2014 Melin, Clin Microbiol Inf, 1
Slide 88: A new vaccine concept
A new vaccine concept
Slide 89: Testing hypothesis for a COPD vaccine
Testing hypothesis for a COPD vaccine Epi studies show association between lung infections & COPD exacerbations1,2 Development plan to support proof of concept NTHi and Mcat: 2 lung pathogens potentially Epi 001 associated with 30-50% of COPD Detailed molecular microbiology study of AE-COPD exacerba
Slide 90: Data and planned filings support positive growth outlook
Data and planned filings support positive growth outlook 2016 2017 2018 2019 2020 2021-2025 Q flu paediatric MMR US filing Shingrix immuno- US/UK Bexsero MenABCWY RSV maternal US filing compromised paediatric data US filing filings efficacy filing Shingrix US, EU, MMR Japan Rotarix liquid GBS matern
Slide 91: R&D programmes to deliver near-term growth and novel immunisation platforms
R&D programmes to deliver near-term growth with significant future opportunities and novel immunisation platforms 3 A new vaccine concept − COPD Longer term R&D Focus 2 − RSV − GBS Near/mid term key R&D focus: − Shingrix 1 − Meningitis − Lifecycle management 91
Slide 92: Introducing the Vaccines panel
Introducing the Vaccines panel GSK’s leading scientists in vaccines Alain Brecx Emmanuel Hanon Vice President Senior Vice President, Vaccine Development Lead - Zoster Head of Vaccines R&D Rip Ballou Giovanni Della Cioppa Vice President Vice President, Head of Rockville R&D Centre Head of Siena R&D C
Slide 93: Q&A
Q&A
Slide 94: Immuno-Inflammation
Immuno-Inflammation
Slide 95: Immuno-Inflammation areas of focus
Immuno-Inflammation areas of focus Immune modulation to alter disease course, induce and sustain remission Rheumatoid Osteoarthritis Systemic Lupus Other immune- Arthritis (OA) Erythematosis mediated (RA) (SLE) diseases • Circa 5.3m RA patients in G7 • Circa 72m OA patients in G7 • Prevalence: 40 -1
Slide 96: Immuno-Inflammation R&D strategy: From symptomatic benefit to sustainable remission
Immuno-Inflammation R&D strategy: From symptomatic benefit to sustainable remission macrophage Targeted Biologicals Targeted Small neutrophil Molecules GSK Pipeline stromal cell Targeting Resistant Early Intervention & T cell Disease Remission Induction plasma cell B cell 96
Slide 97: sirukumab: rheumatoid arthritis
sirukumab: rheumatoid arthritis The anti-IL-6 class is the fastest growing of the biologicals in RA • Collaboration with Janssen Biologics (Ireland) 12 wk data from Phase II study1 • Low frequency sc dosing potential (monthly) ** ** p < 0.05 Response rate (%) 80 63 57 60 • Targets the cytokine 30 **
Slide 98: Clinical improvement in RA is associated with decreased macrophage infiltration
Clinical improvement in RA is consistently associated with decreased macrophage infiltration • Activated macrophages are abundantly GM-CSF plays a key role in activation of expressed in early RA synovial tissue, macrophages at the site of injury or inflammation representing the predominant cell type
Slide 99: GSK3196165 – aGM-CSF, targets key effector cells in RA
GSK3196165 – aGM-CSF, targets key effector cells in RA Aiming to induce remission in early rheumatoid arthritis • In-licensed from MorphoSys AG % EULAR good/moderate response at 4 weeks: Rapid onset of action • Good magnitude of effect with fast onset of action and long duration post treatment 80 Ph
Slide 100: GSK3196165: Potential in hand osteoarthritis
GSK3196165: Potential for disease modification & analgesic activity in hand osteoarthritis (HOA) GM-CSF receptor expression on primary afferent nerve fibres • The macrophage is a mediator of tissue in mouse tibial bone and periosteal nerves destruction in OA • aGM-CSF is effective in animal models o
Slide 101: GSK2982772: RIP1 kinase inhibitor in the clinic
GSK2982772: RIP1 kinase inhibitor in the clinic “a key regulator of inflammation, apoptosis and necroptosis, RIP1 is positioned at a strategic crossroads of multiple signalling nodes in the innate immune response”.1 • New class, oral therapeutic RIP1 kinase inhibition Kinome plot • World leading int
Slide 102: GSK2982772: studies in three indications to start in 2016
GSK2982772: studies in three indications to start in 2016 Key target, compelling target, compelling pre-clinical data 100 * Three Phase II % without severe 80 RIP1 status Blocks severe Clinical Studies clinical studies to dermatitis 60 wt/wt wt/K45A skin inflammation1 progress in parallel 40 K45A/K4
Slide 103: Benlysta: 3rd consecutive positive pivotal study – new data
Benlysta™ (belimumab): 3rd consecutive positive pivotal study – new data • Benlysta – the only medicine to treat systemic Proportion of patients with SLE Responder lupus erythematosus (SLE) to have succeeded Index (SRI) response at week 52 in Phase III. Three other medicines have failed. 100 • Impro
Slide 104: Translating clinical experience into a new hypothesis
Translating clinical experience into a new hypothesis: Phase II experimental study to start 2016 • After B-cell depletion with CASE REPORT aCD20, BLyS levels increase De Vita, Clin Exp Rheum. 2014;32, 490-494 30 • BLyS drives persistence and Serum BLyS (ng/mL) • Severe, refractory Sjögren's syndrome
Slide 105: Early Immuno-Inflammation clinical phase pipeline with multiple first in class assets
Early Immuno-Inflammation clinical phase pipeline with multiple first in class assets Phase I – GSK525762 (BET) GSK2982772 • Multiple first in class assets (RIP1) • Eight key disease mechanisms GSK3050002 * † (aCCL20) • Four biologicals † GSK2831781 * (aLAG3) • Smart clinical development GSK2618960
Slide 106: Four first in class antibodies: GSK2618960
Four “first in class” antibodies in the clinic: GSK2618960 Anti-IL-7R antibody Ectopic lymphoid tissue and increased IL-7R+ cells in salivary glands of patients with Sjögren’s syndrome “First in class” treatment for C IL-7R 14 Sjögren’s syndrome 10 • IL-7R inhibition affects 6 patient pathogenic T c
Slide 107: Four first in class antibodies: GSK3050002
Four “first in class” antibodies in the clinic: GSK3050002 Anti-CCL20 antibody Anti CCL20 prevents CCR6+ cells migration into Collaboration with Morphotek / Eisai inflamed blister in humans in vivo 10 CCR6 pos T cells (%) in blister model Mean change from baseline “First in class” treatment for psor
Slide 108: Four first in class antibodies: GSK2831781
Four “first in class” antibodies in the clinic: GSK2831781 Cell depleting Targeted depletion of LAG-3 T-cells with an antibody (A9H12) anti-LAG3 antibody suppresses the immune reaction to the tuberculin antigen Collaboration with Prima BioMed Pre-dose Post-dose “First in class” treatment for T-cell
Slide 109: Four first in class antibodies: GSK2330811
Four “first in class” antibodies in the clinic: GSK2330811 Anti-OSM antibody OSM expression in skin biopsy 10 “First in class” treatment for P=0.0021 Average number of infiltrates systemic sclerosis • Systemic sclerosis patients 8 have increased OSM serum levels and upregulated OSM and OSM-related g
Slide 110: Four first in class antibodies in the clinic
Four “first in class” antibodies in the clinic All expected to progress to PhII in 2016 Anti-IL-7R antibody Anti-CCL20 antibody Cell depleting Anti-OSM antibody Collaboration with Morphotek / Eisai anti-LAG3 antibody Collaboration with Prima BioMed “First in class” treatment for “First in class” tre
Slide 111: Immuno-Inflammation R&D strategy pipeline
Immuno-Inflammation R&D strategy: From symptomatic benefit to sustainable remission macrophage Targeted Biologicals Targeted Small Molecules neutrophil • Benlysta • • RIP1 GSK Pipeline sirukumab • Anti-GM-CSF • I-BET stromal cell • Anti-IL-7 • Anti-LAG3 • Anti-CCL20 • Anti-OSM Targeting Resistant Ea
Slide 112: Oncology
Oncology
Slide 113: Oncology R&D strategy
Oncology R&D strategy Focusing on 3 areas fundamental to oncology Cancer Epigenetics Long-Term Survival & Reprogram Cancer Cures Cells GSK Pipeline Immuno-Oncology Stimulate Anti-Tumour First in Class Medicines Immunity & Combination Therapy Cancer Stem Cells 113
Slide 114: GSK Epigenetics: an early commitment with a pipeline at the forefront of industry
GSK Epigenetics: an early commitment with a pipeline now at the forefront of industry • World-leading science in epigenetics since 2008 • Team has published 9 papers in Nature & Cell • World-leading academic collaborations • Strategic collaborations with biotech 114
Slide 115: GSK525762: potential first in class BET inhibitor
GSK525762: potential first in class BET inhibitor Potential for broad activity • GSK525762 blocks binding of BET family proteins (BRD2, 3 and 4) to transcriptional mediators changing gene expression including suppressing oncogene expression • Potential use in many potential indications • Broad activ
Slide 116: GSK525762: early evidence of potential clinical benefit
GSK525762: early evidence of potential clinical benefit Potential new treatment for rapidly lethal cancer • Responses observed in NUT midline carcinoma GSK525762 active in NMC, a very difficult to treat cancer – 6 patients treated at 60-100 mg QD with 4 Partial Responses • Solid tumour studies under
Slide 117: GSK525762: potential to treat and reset disease in rheumatoid arthritis
GSK525762: potential to treat and reset disease in rheumatoid arthritis: Extensive preclinical data package for BET inhibition • GSK525762 interferes with stromal cells driving I-BET resets disease in rat collagen-induced arthritis autonomous disease progression in RA 8 1% methylcellulose p.o. 5ml/k
Slide 118: GSK2879552 LSD1 inhibitor: Early signal of efficacy in SCLC
GSK2879552 LSD1 inhibitor: Early signal of efficacy in SCLC • Preclinical data give reason to believe Plot of duration of treatment (days) with Tumour Response (RECIST 1.1 criteria) SCLC • Clinical studies ongoing in Small Cell Lung NE NE Cancer and Acute Myeloid Leukaemia NE NE • Signal of signific
Slide 119: Immuno-Oncology: NY-ESO T-Cell Therapy
Immuno-Oncology: NY-ESO T-Cell Therapy Sarcoma Phase I/II: Individual patient complete response (CR) • TCR T-cell therapy Baseline Day 2: Inflammation Day 100: CR • 50% ORR seen in sarcoma • Ongoing studies in ovarian and other solid tumours and haematological malignancies • Planned studies in combi
Slide 120: Immuno-Oncology: GSK3174998 OX40 agonist mAb
Immuno-Oncology: GSK3174998 OX40 agonist mAb Survival in animal model (CT26) • GSK3174998 is one of four humanised OX-40s OX-40 + PD-1 100 in clinic Percent survival 80 • Dual mechanism: enhancing effector T-cell and 60 aOX40 /aPD-1 suppressing T-regs 40 20 aOX40 • Phase I Study started in eight can
Slide 121: Immuno-Oncology: GSK3359609 first-in-class ICOS agonist antibody
Immuno-Oncology: GSK3359609 first-in-class ICOS agonist antibody • Universal mechanism across ICOS in ipilimumab-treated patients GSK3359609 multiple cancers 80 CD4 ICOS T cells T cell Activation in-vitro • Patient selection biomarker Cell count/mL % of total CD4 T cells 100 CD69+ CD4 T cells 24hr a
Slide 122: Cancer Stem Cells: tarextumab (anti-Notch 2/3)
Cancer Stem Cells: tarextumab (anti-Notch 2/3) • Inhibition of Notch 2/3 Receptors in ALPINE (Phase Ib) Pancreatic Cancer: cancer stem cells gemcitabine/Abraxane* + tarextumab Dose range: TRXT from 5 to 15mg/kg Q2W • Phase Ib: Overall response rate 50 11 of 29 PR (38%) in Nab-P+Gem Cohorts of 38% Tu
Slide 123: Oncology R&D strategy
Oncology R&D strategy Focusing on 3 areas fundamental to oncology Cancer Epigenetics • BET inhibitor (GSK525762) • LSD-1 inhibitor (GSK2879552) Long-Term Survival & Reprogram Cancer • EZH2 inhibitor (GSK2816126) Cures Cells • Epigenetics • Epigenetics GSK Pipeline • Immuno-oncology Immuno-Oncology •
Slide 124: Oncology – Pipeline snapshot
Oncology – Pipeline snapshot Mechanism Pre-clinical Phase I Phase II BET inhibitor (GSK525762) Solid tumours, Heme Malignancies LSD-1 inhibitor (GSK2879552) AML, SCLC EZH2 inhibitor (GSK2816126) Solid tumours, Heme Malignancies † PRMT5 inhibitor (GSK3326595) Solid tumours, Lymphoma Novel small molec
Slide 125: Assets profiled at R&D day by planned filing date
Assets profiled at R&D day by planned filing date See www.gsk.com for full clinical pipeline 2014 2018 2021 to to to 2017 2020 2025 6 NMEs & 5 PLEs 10 NMEs & 5 PLEs 17 NMEs & 5 PLEs Nucala sirukumab mepolizumab tarextumab† GSK2398852+ sirukumab GSK3008348 GSK525762 GSK3196165 Respiratory (mepolizuma
Slide 126: Rare Diseases
Rare Diseases Amyloidosis and Cell and Gene Therapy
Slide 127: Amyloidosis: a complex protein deposition disease with ~50% mortality at 3 years
Amyloidosis: a complex protein deposition disease process with ~50% mortality at 3 years • AL amyloidosis – monoclonal immunoglobulin light chains (plasma cell dyscrasia) (~70% of all cases) • ATTR amyloidosis – hereditary disease caused by variant transthyretin (TTR) protein – acquired disease caus
Slide 128: Two fundamental approaches to treatment of amyloidosis
Two fundamental approaches to treatment: prevent amyloid formation and remove amyloid deposits “Gene silencing” by antisense oligonucleotide Removal of amyloid deposits by –DNA –mRNA –Protein macrophage-mediated clearance Serum amyloid P component (SAP) in blood and all amyloid –Antisense Oligo depo
Slide 129: GSK2998728 RNA targeted transthyretin (TTR) knockdown
GSK2998728 RNA targeted transthyretin (TTR) knockdown ~80% TTR knockdown Mean change - Time profile following 3 loading doses TTR reductions observed in Phase III week 1, then 1 weekly dose (n=65; healthy volunteers) FAP open label extension Mean max TTR reduction = 76% Transthyretin (mean % Chg +/-
Slide 130: CPHPC + Anti-SAP mAb for systemic amyloidosis
CPHPC + Anti-SAP mAb for systemic amyloidosis • Directly targets amyloid deposits that cause Reason to believe – amyloid imaging disease • Proof of concept in systemic amyloidosis – Regression of amyloid in liver, kidney, spleen, etc Before Day 42 after • Potential for accelerated approval anti-SAP
Slide 131: Amyloidosis: a comprehensive R&D approach
Amyloidosis: a comprehensive R&D approach • Similar prevalence to Pulmonary Arterial Hypertension GSK’s dual approach to amyloidosis – Approximately 30,000 cases but currently under-diagnosed • Fundamental mechanism in diverse but 1. “Gene silencing” by 2. Removal of antisense amyloid deposits medic
Slide 132: GSK2696273 for adenosine deaminase severe combined immunodeficiency
GSK2696273 for adenosine deaminase severe combined immunodeficiency: 100% survival at median 7 year follow up 3000 2000 1000 Increased T cell count 0 Baseline Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Actual visit n=12 Severe Combined Immuno- 1.20 Deficiency (SCID) Reduced 1.00 infecti
Slide 133: Gene therapy works in different monogenic diseases
Gene therapy works in different monogenic diseases Innovative collaboration with Telethon and Ospedale San Raffaele • World first ex vivo autologous Pipeline of products stem cell gene therapy filed ADA SCID a • Filing strategy agreed for 2 more Metachromatic Leukodystrophy a Wiskott-Aldrich Syndrom
Slide 134: Cell Gene Therapy clinical effect in MLD
Cell Gene Therapy clinical effect in MLD Motor function by GMFM in LI patients 100 80 GMFM score (%) 60 40 20 0 0 20 40 60 80 100 120 Chronological age (months) Biffi et al. ESCGT 2015 presentation 134
Slide 135: Introducing our experts
Introducing our experts GSK’s leading scientists in immuno-inflammation, cancer research, amyloidosis and CGT Paul-Peter Tak Ravi Rao John Bertin Senior Vice President, Vice President, Medicines Vice President, Head Immuno- Development Leader & Head Pattern Recognition Inflammation (II) TAU Head Uni
Slide 136: Assets profiled at R&D day by planned filing date
Assets profiled at R&D day by planned filing date See www.gsk.com for full clinical pipeline 2014 2018 2021 to to to 2017 2020 2025 6 NMEs & 5 PLEs 10 NMEs & 5 PLEs 17 NMEs & 5 PLEs Nucala sirukumab mepolizumab tarextumab† GSK2398852+ sirukumab GSK3008348 GSK525762 GSK3196165 Respiratory (mepolizuma
Slide 137: Q&A
Q&A