Innovative Pipeline Sir Andrew Witty
3 November 2015 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 historical or current facts. They use words such as ‘anticipate’, ‘estimate’, ‘expect’, ‘intend’, ‘will’, ‘project’, ‘plan’, ‘believe’, ‘target’ and other words and terms of similar meaning in connection with any discussion of future development, operating or financial performance. In particular, these include statements relating to future actions, prospective products or product approvals, future performance or results of current and anticipated products, sales efforts, expenses, the outcome of contingencies such as legal proceedings, and financial results.
Other than in accordance with its legal or regulatory obligations (including under the UK Listing Rules and the Disclosure and Transparency Rules of the Financial Conduct Authority), the Group undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Investors should, however, consult any additional disclosures that the Group may make in any documents which it publishes and/or files with the US Securities and Exchange Commission (SEC). All investors, wherever located, should take note of these disclosures. Accordingly, no assurance can be given that any particular expectation will be met and shareholders are cautioned not to place undue reliance on the forward-looking statements.
Forward-looking statements are subject to assumptions, inherent risks and uncertainties, many of which relate to factors that are beyond the Group’s control or precise estimate. The Group cautions investors that a number of important factors, including those in this document, could cause actual results to differ materially from those expressed or implied in any forward-looking statement. Such factors include, but are not limited to, those discussed under Item 3.D ‘Risk factors’ in the Group’s Annual Report on Form 20-F for 2014 and those discussed in Part 2 of the Circular to Shareholders and Notice of General Meeting furnished to the SEC on Form 6-K on November 24, 2014. Any forward- looking statements made by or on behalf of the Group speak only as of the date they are made and are based upon the knowledge and information available to the Group on the date of this report.
2 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+ outside US environment year olds & Europe opportunity new babies by 2020 uncertain by 2020 (+20%)
3 R&D Strategy: Reliable fill & flow with greater novelty and improved return on investment
Accelerate Focus where science Improve balance ReduceAcute fixed cost Discovery output is innovative internal vs external andcomplicated improve ROI infectious diseases • Now have 30 DPUs, of which • Of the ~40 assets profiled today, • 60% of NMEs* in the clinic are • 20% faster study execution two thirds are from the original 80% of new molecules, home-grown, 40% partnered or times^ biologicals and vaccines are in-licensed 2009 set. Average 20% turnover • Pharma R&D headcount every 3 year cycle potentially 1st in class • >1,500 collaborations inclusive reduced from 12,000 to 8,500 • 65% of NMEs* in the clinic were • Almost 50% of clinical stage of academic, public-private since 2008, reduced to 2 global either discovered or worked on NMEs* are biopharm, CGT, or partnerships, biotech and pharma R&D hubs oligos. i.e. non-traditional white by the DPUs pharma • Balance discovery and pill development (pharma split 38% • Average of 60-65 publications • Competitive advantage through Discovery; 62% Development) annually in world class journals epigenetics, cell & gene across pharma and vaccines • Divested marketed oncology technology, adjuvants, self portfolio for $16bn amplifying RNA, inhaled
technology, chimp adenovector
To deliver multiple launches per year *NMEs: Phase I – III/submitted, per pipeline chart; † Pipeline = Phase I-III/submitted; ^ comparison vs peers based on CMR data. 4 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 28 first approvals of new products generating £1.3 billion in ~ 20 Phase III NME/PLE starts molecules, vaccines or significant 2015 YTD in 2016/17 combinations, generating
Launches £2.6 billion sales in 2014 + 5 additional Phase III NMEs/PLEs
†
~£6bn loss to generics + Avandia Avodart (Q4 2015), Advair Reduced generic exposure Generics
* Includes key recent and near-term launches plus late-stage assets. Rx: Breo, Anoro, Incruse, Arnuity, Tanzeum, Nucala, Tivicay, Triumeq. Vx: Menveo, Bexsero, Shingrix. † A number of assets in the portfolio will face generic competition in this time frame, the most significant of which is Advair PLE= New formulations or combinations 5
basis Sterling a on quarters respective the in decline and Growth ^
6
Arnuity , Incruse , Anoro , Breo Rx: as: defined products New * Bexsero , Menveo : Vx . Triumeq , Tivicay , Tanzeum ,
£182m
£141m £135m
Advair / Seretide
decline^
£221m
£321m
£412m growth*^ product New
15 Q3 15 Q1 15 Q2 Q1 Q3 Q2
New product growth more than offsets Advair decline Advair offsets than more growth product New
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 GSK2315698 IL-6 mAb Alpha V beta 6 BET inhibitor GM-CSF mAb IL-5 mAb SAP mAb + SAP integrin Respiratory Rheumatoid Nasal Pancreatic depleter antagonist Therapy syncytial virus Severe Asthma Arthritis Polyposis Cancer, SCLC Amyloidosis Severe Asthma IPF Resistant RA RA, OA prophylaxis
mepolizumab GSK2696273 mepolizumab GSK525762 GSK2998728† danirixin Long acting IL-5 GSK2330811 GSK2696277†^ COPD IL-5 mAb Ex-vivo stem CGT IL-5 mAb BET inhibitor TTR production CXCR2 mAb (NBE) OSM mAb Ex-vivo stem CGT Solid Tumours, inhibitor antagonist Haematological TTR Systemic Beta COPD ADA-SCID HES Malignancies Cardiomyopathy COPD Asthma, Others Sclerosis Thalassemia COPD vaccine
mepolizumab GSK2696274 dolutegravir + GSK2879552 daprodustat* GSK2269557 IL5/13 bispecific GSK2618960 daprodustat* IL-5 mAb Ex-vivo stem CGT lamivudine FDC LSD1 inhibitor Prolyl PI3 kinase delta antibody IL-7 receptor Prolyl Respiratory Integrase Acute Myeloid hydroxylase inhibitor mAb hydroxylase Metachromatic inhibitor+NRTI Leukaemia, inhibitor Sjogren’s inhibitor (topical) HIV / Infectious Diseases EGPA Leukodystrophy HIV SCLC Anaemia of CKD COPD, Asthma Asthma Syndrome Wound Healing Immuno-Inflammation fluticasone GSK2696275 cabotegravir GSK3174998 MenABCWY GSK2862277 GSK2878175 GSK2831781 mepolizumab furoate+vilanterol Ex-vivo stem CGT Long acting OX40 agonist mAb US filing TNFR1 dAb NS5B inhibitor LAG-3 mAb IL-5 mAb Oncology +umeclidinium integrase Solid tumours, Meningococcal Rare Diseases ICS/LABA/LAMA Wiscott-Aldrich inhibitor Haematological A,B,C,W and Y Acute Lung Autoimmune Severe Atopic COPD Syndrome HIV, HIV PrEP Malignancies disease prophylaxis Injury HCV Diseases Dermatitis Other Pharma
dolutegravir + GSK2998728† gepotidacin GSK3377794† # GSK2245035 GSK3228836† GSK2982772 RSV maternal Vaccines rilpivirine TTR production Type 2 NY-ESO-1 TCR TLR7 agonist Antisense RIP1 kinase Integrase inhibitor inhibitor topoisomerase Sarcoma, Mult. oligonucleotide inhibitor Respiratory † Subject to exercise of option + NNRTI inhibitor Myel., Melanoma Psoriasis, RA, syncytial virus # Subject to collaborator agreement HIV FAP Bacterial Inf. Ovarian, NSCLC Asthma HBV UC prophylaxis ^ EU filing * USAN, INN approval pending Benlysta Shingrix sirukumab GSK3359609 GSK3191812 belimumab + GSK3050002 GBS maternal Subcutaneous IL-6 mAb ICOS agonist mAb TSLP dAb CD20 CCL20 mAb Planned to be filed post 2025 BLyS mAb Solid tumours, BLyS+CD20 Group B Herpes Zoster Giant Cell Haematological Sjogren’s Psoriatic streptococcus SLE prophylaxis Arteritis Malignancies Asthma Syndrome Arthritis prophylaxis See www.gsk.com for full clinical pipeline 7 Focus on delivering innovative and sustainable presence in 6 key areas
HIV / Infectious Respiratory Vaccines Diseases
Immuno– Oncology Rare Inflammation Diseases
8 Focus for today: Innovation to deliver products of value
Patrick Vallance Moncef Slaoui President, Pharmaceuticals R&D Chairman of Vaccines
9 Patrick Vallance President, Pharmaceuticals R&D 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 Science) Company 1 • Focus on preventative and curative • In 2014 and 2015 to date, GSK Company 2 medicines scientists listed as co-authors in more Company 3 than 1,600 publications • Strong focus on patient input Company 4 • 80% of pre-clinical to Phase II assets • Quality of life study endpoints • All first cycle approvals since 2012 have a novel mechanism of action • 10% faster in time to file approval than industry average • Target sciences initiative with • Clinical study cycle times 20% faster than EBI/Sanger & Altius Institute in Seattle average • Cost per patient visit 30% less than 2008 • Molecule quality focus
Partnership Collaborations with academia, biotechs, pharmaceutical companies and regulators 11 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
Biotech Industry Academia
12 HIV / Infectious Diseases 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 deaths due to lower 2m new infections Hepatitis C1 respiratory tract infections2 • More than 780k people die annually1 each year • 350-500k people die each • Increasing antimicrobial • Resistance, adherence year drug resistance (MDR) • HBV evades immune and addressing long-term system, with limited • Need for a cure completed • Hospitalised infections & toxicities remain areas of options for durable in a single visit complications have direct significant unmet medical remission costs >$35bn annually in need US3 • The ultimate goal is • Pathophysiology & tissue remission and cure damage suggest aberrant host immune responses as key driver
1 WHO 2015; 2 WHO 2014; 3 J Med Econ 2013 14 Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure
HIV Innovative Long -acting
Treatment Treatment
Regimens
HCV/HBV Prevention Remission & Cure
GSK GSK Pipeline
Acute complicated infectious disease
15 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 Barrier to Resistance No food requirements • No resistance mutations selected in first line failures (one patient had DTG/RPV: Planned launch H1 2018 E157Q/P mutation without decreased 2-drug STR for HIV treatment in suppressed patients, QD susceptibility to dolutegravir) Simplification - Potential benefit on tolerability and drug burden (ViiV Healthcare - Janssen sponsored) • Limited resistance mutation evolution in experienced patients on failure • Distinct resistance profile compared Triumeq™ (abacavir/dolutegravir/lamivudine): Launched 2014 to other INIs (RAL, EVG) 3-drug STR for HIV treatment, QD Only currently available DTG containing Single Tablet Regimen (STR) Favorable PK Profile • Booster free • No food requirement for adequate Tivicay™ (dolutegravir): Launched 2013 exposure For HIV treatment in combination with other ART, QD
Well tolerated Approved Investigational
ViiV Healthcare is a specialist joint venture solely dedicated to HIV, owned by GSK, Pfizer and Shionogi 16 PADDLE (Pilot Antiretroviral Design with Dolutegravir and LamivudinE): Investigator sponsored study design
Patient Base line viral • Investigator sponsored study # load Week 8 Week 24 1 10.909 < 50 < 50 • 2 tablet treatment 2 10.233 < 50 < 50 3 151.569 < 50 < 50 4 148.370 < 50 < 50 • ARV naive patients 5 20.544 < 50 < 50 6 14.499 < 50 < 50 7 18.597 < 50 < 50 • 2 cohort study 8 24.368 < 50 < 50 9 10.832 < 50 < 50 • Open label single arm 10 7.978 < 50 < 50 11 273.676 < 50 < 50 12 64.103 < 50 < 50 Phase IV, pilot, open-label, single arm exploratory trial 13 33.829 < 50 < 50 14 15.151 < 50 < 50 1st cohort 2nd cohort 15 23.500 < 50 < 50 16 3.910 < 50 < 50 (n= 10) (n= 10) 17 25.828 < 50 < 50 18 73.069 < 50 < 50 19 106.320 < 50 < 50 DTG 50 mg QD DTG 50 mg QD 20 7.368 < 50 < 50 LMV 300 mg QD LMV 300 mg QD From week 8 onwards all patients VL was
Adapted from Cahn et al, EACS 2015, LBPS4/1 undetectable (pVL < 50 copies/mL) 17 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) 8/8 protected 800mg IM (split)
cabotegravir LA ) 80 1 mL 4*PA-IC90 untreated
(%) 100 60
80 100% Protection in PA-IC90
3 60 40 NHP Rectal Challenge Aviremic Plasma CABPlasma(g/
0.1 40 Cabotegravir 10 mg (n=60)
(%) Patients Cabotegravir 30 mg (n=60) 8/8 infected 20 Cabotegravir 60 mg (n=61) 20 Efavirenz 600 mg (n=62) p<0.0001 0 0 2 4 8 12 16 24 28 32 36 40 48 60 72 84 96 Visit (week) 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Proportion of patients with HIV-1 RNA concentration of less than 50 copies per mL 0 2 4 6 8 10 12 14 16 18 20 Time (weeks) by visit in the intention to-treat exposed population Error bars indicate 95% CI Weeks post first challenge 1Spreen et al, JAIDS 2014;67(5):481-486 2Margolis et al, Lancet Inf Dis 2015;15(10):1145-1155 3Andrews et al, Science 2014;343(6175):1151-4
18 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 2019/2020 CAB LA + RPV LA switch studies (transition from oral therapy to long-acting)
Mid-2016 PrEP Phase III start (men) HIV PREVENTION CAB LA monotherapy vs. TDF/FTC (Truvada) in at-risk men who have sex with men/transgender women CAB LA monotherapy (Collaboration with third party being considered)
Planned launch: End-2016 PrEP Phase III start (women) 2020+ CAB LA monotherapy vs comparator in at-risk women (Collaboration with third party being considered)
19 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 virologic suppression 286 subjects qualified for entry into maintenance phase and were randomised 2:2:1 onto: 4 week injections with CAB LA + RPV LA (Q4W); 8 week injections with CAB LA + RPV LA (Q8W) or continuation of oral CAB + NRTIs
• Through 32 weeks on 2-drug maintenance therapy with CAB LA and RPV LA, 95% (Q8W) and 94% (Q4W) of subjects were virologic successes (VL<50) compared to 91% of subjects continuing three drug oral CAB + NRTIs
• Adverse events (AEs) leading to withdrawal were 5% (n=6) for Q4W, 2% (n=2) for Q8W, and 2% (n=1) for oral CAB + NRTIs. The most common AE was injection site pain (93% of injection recipients)
• Detailed analyses just starting
20 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 collaboration to be announced later this week Nano-formulation Potential targets for neutralisation V1V2 Glycan: N332 Glycan supersite: PG9, PG16 PGT121, PGT128 PGT141-145 10-1074 CAP256-VRC26.25 PGDM1400
CD4 Binding site: VRC01, PG04, + CH31, 3BNC117, Trimer (gp120/41): 12A12, VRC13, 8ANC195 VRC01-LS, PGT151 VRC07-523-LS, 35022 gp41 MPER: Z258-N6 2FS, 4E10 10e8 Viral membrane
Huang et al. Nature 2014;515(7525):138-42 A pilot clinical combination study of VRC01 and cabotegravir is planned for 2016 start 21 GSK & Regulus combination offers potential for a single administration treatment for HCV
• RG101 lowers viral load Single dose RG-101
Prolonged VL declines in HCV patients
• GSK2878175 lowers viral -1 RG-101 2 mg/kg n=14 load RG-101 4 mg/kg n=14 placebo n=4 -3 • Both molecules have
potential for prolonged -5 viral load declineload viral 0 1 2 3 4 5 6 7 8 PK/PD activity Weeks Log10reduction of HCV EASL 2015. Van Der Ree et al. J. Hepatology . 2015;62: S261
• Prolonged pan-genotype Single dose GSK175-LA Potent anti-HCV activity Prolonged PK in animals and anti-HCV activity
(2 oral doses) GSK175-LA
0 Pbo GSK744-LA • Potential single -1
30 mg
administration option -2 HCV RNA HCV RNA 60 mg
10 -3
reduction
concentration log • Clinical combination study -4 Log10 Relative 0 2 4 6 8 10 12 14 starts 2016 0 5 10 15 Days Weeks AASLD 2014. Gardner et al. Hepatology .2014;60:1164A) GSK: data on file 22 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 • Entered collaboration with 100 saline 100 Isis Pharmaceuticals in saline
2010 10 – GSK contributed target, 10 mg/kg
Isis provided platform 1 10 10 mg/kg (% before treatment)(%before
(% before treatment)(%before
& discovery 100 mg/kg 0.1
HBsAg • Lead compound HBeAg 100 mg/kg
GSK3228836 0.01 1 Serum – Phase II start planned 0 1 2 3 4 5 6 7 Serum 0 1 2 3 4 5 6 7 2016 Week Week GSK, data on file.
Note: GSK3228836 subject to exercise of option by GSK
23 Infectious Diseases strategy: from innovative treatment regimens to the pursuit of cure
HIV Innovative Long -acting
Treatment Treatment
Regimens
HCV/HBV Prevention Remission & Cure
GSK GSK Pipeline
Acute complicated infectious disease
24 First in a new class of antibacterials: gepotidacin (GSK2140944) – a topoisomerase inhibitor
• Novel mechanism with bactericidal 100
activity against MDR pathogens 80 All gepotidacin treated survived (all organs culture negative) • Promising safety & efficacy profiles 60 in Phase II studies 40 All untreated died • Effective against key resistant 20 Only novel class antibacterial currently in clinical development Percent survival Percent to demonstrate activity in FDA accepted model of plague strains: 0 – MDR MRSA, MDR E.coli & Drug 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 resistant N.gonorrhoeae 10 day treatment Days
• Potential to address multiple Quinolone conventional & bio-threat indications Gepotidacin DNA ‘class’ • Progressed via successful partnerships with BARDA & DTRA
Enzyme Planned Filing: 2019 for resistant infections. Gepotidacin binds to a novel site on gryase Discussions with FDA on Nature Struc Mol Biol, 2010,17;465 plague indication. MDR: multi-drug resistant; DTRA: Defense Threat Reduction Agency (US DoD); BARDA: Biomedical Advanced Research & Development Authority (US HHS) 25 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
Regimens − HCV
− HBV HIV, HCV, HBV HIV, HCV, HBV
Prevention Remission & Cure
GSK GSK Pipeline HIV HIV, HCV, HBV (Qura)
− gepotidacin − tafenoquine − i.v. danirixin
26 Respiratory 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 • Idiopathic Pulmonary Fibrosis for mild/moderate asthma 2030 (IPF): median survival of just 2-5 • Major unmet medical need in • Longitudinal studies (e.g. years, 2 IPF products approved severe asthma ECLIPSE) helping to identify • Urgent need to improve symptoms − 5-10% of asthma patients prognostic biomarkers (e.g. and delay disease progression fibrinogen) − 60% of cost burden • Acute Lung Injury (ALI): hospital • Immune modulation offers • Targeting underlying drivers of mortality rates of up to 50% disease progression is key potential for better disease control • Need to identify better clinical path and even remission for drug development
28
29
cell dendritic
GSK Pipeline
inducing - Remission Inhaled Daily Once
neutrophil
Biologicals
eosinophil
Targeted Targeted Extended Duration Duration Extended Biologicals
primary disease modification disease primary
Asthma R&D strategy: from secondary prevention to to prevention secondary from strategy: R&D Asthma Nucala™* (mepolizumab) demonstrates significant reduction in exacerbations
Nucala (subcutaneous anti-IL-5 mAb): mepolizumab (s.c. or i.v.) reduced the number of • Straightforward patient selection & asthma exacerbations in patients with severe eosinophilic asthma biomarker 250
• 53% reduction in exacerbations placebo (n=191)
• 61% reduction in ER visits/ hospitalisations 200 • Improvement in health status by 7 points (SGRQ) 150 mepolizumab 75mg, • Significant reduction in daily oral intravenously (n=191) corticosteroid dose while maintaining 100 control seen in trials • Dosing every 4 weeks, no weight mepolizumab 100mg, 50 subcutaneously (n=194)
adjustment required exacerbationsCumulative • Well tolerated 0 Indication: Severe refractory eosinophilic asthma 0 4 8 12 16 20 24 28 32 Positive CHMP: 24 Sep 2015 Week PDUFA : 4 Nov 2015 Adapted from MENSA study, Ortega et al. NEJM 2014; 371:1198-207 *The name Nucala is not approved for use by the FDA or EMA. 30 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
Earliest launch Q4 2015/ Q4 2015 Launched 2017 2017 2019 2019 assumption* Q1 2016
Mechanism Anti-IL-5 Anti-IgE Anti-IL-5 Anti-IL-5R Anti-IL-13 Anti-IL-13 Anti-IL-4Rα
Delivery mechanism SC SC IV SC SC SC SC
Efficacy data Ph III Phase III ongoing Safety data Ph III
*Based on published filing date plus average review times 31 Nucala* has potential in other indications Anticipated file timelines
2014 2016 2017 2018 2019 2020+ to 2015
Asthma – Evidence Generation
COPD – Evidence Generation
Eosinophilic granulomatosis with polyangiitis (EGPA)
Hyper-eosinophilic syndrome (HES)
Nasal polyposis / Chronic rhinosinusitis
Atopic dermatitis
*The name Nucala is not approved for use by the FDA or EMA and may not be approved for additional indications. 32 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) epithelial immune response in asthma • IL-6: key inflammatory driver and genetic association of this • Inhaled domain antibody (dAb) directly targets site of action pathway in asthma and reduces systemic exposure to improve risk:benefit profile • Expected to improve symptoms and exacerbations • Clinical proof of concept demonstrated for anti-TSLP approach • Phase II study start in 2016 • Phase I start in 2016
Elevated IL-6 associated with eosinophilic-neutrophilic Target engagement after inhaled delivery of dAb: exemplar
inflammation and decreased pulmonary function (FEV1) Inhaled TNFR1 dAb reduced endotoxin (LPS) induced in asthma patients inflammation in healthy volunteers
10
500
400 120 mL / 8 IL-6 * FEV 4 400
100 1
300 6 ) mL 80 * 300 200 60 * mL pg/ # 4 200 *
(% predicted) (%
40 * (pg/ 100 1
20 2 100
Lung cytokines Lung Lung cells 10cells Lung FEV * 0 0 0 0 Normal Eosinophilic Neutrophilic Eosinophilic + Normal Eosinophilic Neutrophilic Eosinophilic + cell count bronchitis bronchitis neutrophilic cell count bronchitis bronchitis neutrophilic Lung IL-6 IL-8 MIP 1a (n=29) (n=30) (n=11) bronchitis (n=29) (n=30) (n=11) bronchitis (n=6) (n=6) neutrophils *p < 0.05 vs neutrophilic bronchitis and eosinophilic bronchitis groups * p<0.05 t=test #p < 0.05 vs eosinophilic bronchitis group n=18 subjects per group placebo inhaled TNFR1 dAb (26mg) Chu, Allergy Asthma & Clinical Immunology.2015;11:14 Data on file (study TFR116236) * sirukumab is part of a GSK Janssen Biologics (Ireland) collaboration 33
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
Expected file 2014 2021-25 2021-25 2021-25 2021-25
Status Filed Phase II start 2016 Phase I/II start 2017 Phase I start 2016 Preclinical
Moderate-severe Asthma Severe without elevated Moderate-severe Severe eosinophilic Moderate-severe eosinophilic eosinophilic and eosinophils eosinophilic segment neutrophilic
Key cytokine in epithelial Additive efficacy of two Reason to Clinical data and strong IL-6 is key driver of non- Extended pharmacology allows immune response; complimentary believe mechanism rationale eosinophilic inflammation six monthly dosing Inhaled - directly targets mechanisms, in six site of action monthly dosing 34 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 mL 10000 Week 8
Increase in IP-10 • Clinical data demonstrate target engagement 20 ng 1000 levels 24 hours after (IP-10) with no tachyphylaxis last dose of 8 weekly treatments
Target Pbo
10 10 95% and CI (pg/ - • Protection from nasal allergen challenge up to 100 3 weeks after last dose engagement
Pre-dose 24hrs Mean Mean IP
• Weekly treatment may induce remission from 1 week post treatment 3 weeks post treatment
asthma 9 9 Total nasal symptom score • Phase II asthma study 2016 7 7 (TNSS) reduced after 8 weekly 5 5 treatments and
maintained 3 weeks
3 3 after last dose Mean TNSS and and Mean 95% TNSS CI Status: Phase IIa n=6 n=13 n=6 n=13 pbo pbo Probability of 20 ng 20 ng Indication: Asthma remission any reduction Protection from from Protection 0.92 0.84
Planned Filing: 2021-2025 challenge allergen GSK, data on file (study TL7116958) 35
36
dAb TSLP - Anti •
Ellipta™ Incruse •
™ Ellipta Arnuity •
agonist TLR7 • Ellipta Breo / Relvar •
™
GSK Pipeline
inducing - Remission Once Daily Inhaled Daily Once
IL - Anti • 5/13 -
5/13 - IL - Anti •
TSLP TSLP - Anti • dAb
acting anti acting - Long • 5 - IL -
sirukumab •
Nucala •
Biologicals
Targeted Targeted Extended Duration Duration Extended Biologicals
From secondary prevention to primary disease modification disease primary to prevention secondary From
Asthma R&D strategy: R&D Asthma
37
cell epithelial
GSK Pipeline
Function Function
Preserve Lung Lung Preserve Once Daily Inhaled Daily Once
neutrophil
Exacerbations
Targeted Targeted Infection Driven Driven Infection Biologicals eosinophil
Targeting the fundamental drivers of disease disease of drivers fundamental the Targeting
COPD R&D strategy: R&D COPD
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 • EU Closed Triple filing: end 2016 (lung function) (Study 201314, ITT pop n=236)
• US Closed Triple filing: H1 2018 (exacerbations) UMEC add on vs. Advair • Triple therapy already part of some clinical practice1 (Study 116136, ITT pop n=409) 1Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2015 UMEC add on vs. Advair (Study 116135, ITT pop n=404)
Eosinophil signature being evaluated prospectively in IMPACT study UMEC add on vs. Breo (Study 200109, ITT pop n=412) FF/UMEC/VI (n=4000) UMEC add on vs. Breo (Study 200110, ITT pop n=412) Current COPD FF/VI Follow-up meds (n=4000) 0 20 40 60 80 100 120 140 160 180 200
UMEC/VI Difference in trough FEV1 24 hours after last dose (mL, 95% CI) (n=2000) Improvement 38 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 • Inhaled delivery offers potential efficacy/safety
advantage and opportunity for combination therapy Angulo et al. Science 2013; 342: 866 • Target engagement demonstrated in healthy Directionality of neutrophil migration is aberrant in COPD smokers (PIP3) patients and corrected by PI3Kδ inhibition - in vitro • GSK2269557 on top of standard of care in COPD shows decreased markers of inflammation • Currently testing in exacerbating COPD patients and Phase IIb studies to start 2016/17
Status: Phase IIa Indication: COPD exacerbation Planned Filing: 2021-2025 Healthy control COPD Sapey et al. AJRCCM 2011;183:1176 39 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 engagement demonstrated with danirixin
(neutrophil activation biomarker, CD11b) 25
RS) - • Competitor compounds produced clinical 20 effects, but with reduction in blood neutrophils1 15 • In the clinic, danirixin has efficacy at a dose not
associated with reduced blood neutrophils 10 • COPD Phase IIb start 2016 5
• Influenza infection Phase IIa study ongoing Total SymptomTotalScore (EXACT 0 1Am J Respir Crit Care Med 2015;191:1001–1011 0 20 40 60 80 100 120 140 160 180 Day Status: Phase IIa Indication: Symptomatic COPD placebo (n=35 in study) danirixin 75mg (n=35 in study) Planned Filing: 2021-2025 GSK, data on file (study 200163)
40
41
δ PI3K •
+FF GSK961081 •
device) (Ellipta Triple Closed •
Ellipta Incruse •
danirixin danirixin • Ellipta Breo / Relvar •
GSK Pipeline
Anoro • δ PI3K • Ellipta ™
Preserve Lung Function Lung Preserve Inhaled Daily Once
danirixin
•
Nucala • δ PI3K •
Exacerbations Exacerbations
Infection Driven Driven Infection Biologicals Targeted
Targeting the fundamental drivers of disease disease of drivers fundamental the Targeting
COPD R&D strategy: pipeline strategy: R&D 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 dendritic cell
42 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 (deposition of Tc - labelled salbutamol in lungs of IPF patients supports inhaled approach) • Displacement of αvb6 PET ligand allows dose ranging in patients IPF Healthy volunteer vβ6 PET ligand FDIH An inhaled dAb platform for acute lung injury (GSK2862277) • High sTNFR1 levels associated with high mortality
• dAb blocks TNFR1 signalling without impacting beneficial TNFR2 signalling • Inhaled TNFR1 dAb reduced endotoxin (LPS) induced inflammation in healthy volunteers • Now in Phase II study mAb (grey, blue, red) vs. dAb (green)
43 PHI and Oxygen Sensing 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 Hgb 10.0-11.5 g/dL (n=96) convenient titration, potential for improved CV safety 12.0 Pre-treatment phase Treatment phase
Phase II summary (IIa and new IIb) 11.5
) C C C 2 11.0 C G G • Phase IIa data recently published dL G G C C G
(g/ 10.5 G • Raises Hgb in dialysis and non-dialysis subjects, C
either naïve to or switching from rhEPO 10.0 G C G G C Hgb • Low dose (most subjects 10mg); Simple titration 9.5 daprodustat rhEPO regimen 0.0 • Durable effect (up to 6 months in Phase IIb) -4 Day 0 4 8 12 16 20 24 • Minimal elevation in EPO levels; No BP increase 1 BL Visit (weeks) • Safety profile consistent with CKD • Phase III start 2016
Status: Phase II Indication: Treatment of anaemia of CKD in subjects 1 USAN, INN approval pending on dialysis and not yet on dialysis 2 J Am Soc Nephrol Oct 22, 2015 (epub) Planned Filing: 2019 Japan, 2021 US/ROW 3 GSK, data on file (Study PHI113737) 45 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 subjects non-dialysis and dialysis Flexible dose regimen: Non-Dialysis QD Dialysis QD / TIW Phase III designed for clear assessment of CV risk Single CV outcome trials for ND and HD Inhibition of collagen-4-hydroxylase (cardiac tox risk) No
Concern for hepatotoxicity (e.g. exclusion of No acetaminophen in phase III trials)
46 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 systemic exposure and no Hgb elevation – Efficacy data on wound healing in 2016 Muscle Injury – Novel muscle repair activity discovered in pre-clinical injury model daprodustatdaprodustat reduces reduces total CPK CPK release release over 72 hours
at 48 hours – Phase I: Reduction in muscle injury in healthy volunteers 16000 14000 (IU/L) 12000 Future potential expansion into other anaemia indications 10000 8000 – Myelodysplastic Syndrome (MDS) 6000 4000 2000 n=15 n=15
– Peri-surgical anaemia (ortho, GI, CV) 0 Total CK release CK Total placeboPLACEBO GSK1278863daprodustat 50 50mgMG
GSK, data on file (Study PHI20084) 47 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 Vice President, Vice President, Head Vice President, Head Respiratory TAU Refractory Respiratory Head Unit Physician Inflammation DPU Respiratory
John Lepore Ruchira Glaser Senior Vice President, Clinical Development Director, Head Metabolic Pathways Metabolic Pathways and and Cardiovascular Cardiovascular
48 Q&A Moncef Slaoui Chairman of Vaccines R&D programmes to deliver near-term growth with significant future opportunities and novel immunisation platforms
A new vaccine concept 3 − COPD
Longer term R&D Focus − RSV 2 − GBS
Near/mid term key R&D focus: − ShingrixTM 1 − Meningitis − Lifecycle management
RSV=Respiratory Syncytial Virus; GBS=Group B Streptococcus; COPD=Chronic Obstructive Pulmonary Disease 51 ShingrixTM
Shingrix™ is not approved for use by the FDA or EMA 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 individuals
Estimated to have <25% coverage in US*
2014 reported sales of $868m (>$600m in US)
*CDC: MMWR, February 2015; http://www.cdc.gov/Mmwr/preview/mmwrhtml/mm6404a6.htm; Zostavax™ US PI Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Zostavax data based on US PI. 53 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 individuals in 2017
Expect US, EU, Japan filings in 2H 2016
Expected to contribute ~1/3 of 2020 sales growth targets for GSK vaccines
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. Shingrix data based on ph III clinical trials. 54 Shingrix - Efficacy against shingles
100 90
80
%
- 70 60 50 40 30
20 Efficacy against shingles shingles against Efficacy 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. Shingrix data based on ph III clinical trials. 55 Existing vaccine - Efficacy against shingles
100
90
%
80 - 70 60 50 40 30
20 Efficacy against shingles against Efficacy 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; Shingrix™ and Zostavax™ have not been tested head to head. Zostavax data based on US PI.
Shingrix - Immune response across age segments
Frequency of gE-specific CD4+ T cells by age groups
3500
3000
2500
2000
1500
1000
500
Number of CD4+ T cells per million per cells TCD4+ of Number 0 5050-59-59 yrs 6060--6969 yrs 7070-79-79 yrs ≥ 80≥ 80 yrs
saline gE/saline gE/AS01B
Chlibek et al. J Infect Dis 2013; 208:1953-61 Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Shingrix data based on clinical trials. 57 Existing vaccine - Immune response across age segments
vaccine placebo
12
9
6
3
Responder cell frequency value frequency cell Responder 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 Zostavax™ have not been tested head to head. Zostavax data based on published data. 58 Shingrix - Efficacy against PHN PHN: post herpetic neuralgia, a severe complication of zoster
100 90
80
%
- 70 60 50 40 30
Efficacy against PHN PHN against Efficacy 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™ have not been tested head to head. Shingrix data based on ph III clinical trials. 59
Existing vaccine - Efficacy against PHN PHN: post herpetic neuralgia, a severe complication of zoster
100 90
80
%
- 70 60 50 40 30
Efficacy against PHN PHN against Efficacy 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 been tested head to head. Zostavax data based on published data. 60 Shingrix - Duration of protection against shingles
100
%
- 80
60
40
20 Efficacy against shingles shingles against Efficacy 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 trials. 61
Existing vaccine - Duration of protection against shingles
100
%
- 80
60
40
20 Efficacy against shingles shingles against Efficacy 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 published data. 62 Immune response persistency is a good predictor of duration of efficacy
Shingrix immune response
10000
GMF)
1000
cells / cells million cells -
100
specific specific CD4+ T
-
(geometric mean frequency ( gE 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 head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Shingrix data based on clinical trials. Shingrix: a potentially significant advance in vaccination to prevent shingles
High overall vaccine efficacy across 2016 2017 2018 2019
identified age groups, including oldest
persons
Persistence of vaccine efficacy up to 4 years
across all ages H2: US, EU, Japan Filings Six-year persistence of immune response, modeled to persist above baseline for at Planned/ongoing studies: least 15 years (based on 6 year data) Vaccine co-administration
Revaccination of Zostavax* population Clinically acceptable reactogenicity Comparative tolerability
AS01 adjuvant = new platform for elderly vaccines
Annual capacity of ~25-30m doses by 2020 Phase III efficacy study in immuno-compromised
*Zostavax is a trademark of Merck & Co 64 Not based on head to head data; Shingrix™ and Zostavax™ have not been tested head to head. Shingrix data based on clinical trials.
Meningococcal Meningitis 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
2 0.6 Changes in serogroup distribution in US over time
0.4 0.2
0 <5 5-14 15-24 25-39 40-64 ≥65 1989- 12 2005 2013 4 1991 10 UK 8
Number of cases per100,000 of casesNumber 6 4 B C Y W, A & Other 2 0 <5 5-14 15-24 25-44 45-64 ≥65
Sources: 1) CDC http://goo.gl/RykLaI; Eurostat http://goo.gl/3wp9pp; UNICEF http://goo.gl/DD8pXp 2) Jackson & Wenger MMWR 1993 http://goo.gl/fsbbBz; Active Bacterial Core Surveillance: http://goo.gl/riji5X 3) CDC http://goo.gl/PPtAEj; US Census Bureau https://goo.gl/liNpPU 4) UK.gov https://goo.gl/NxThrj Office for National Statistics http://goo.gl/GJLRpX 66 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 – ACIP recommendation for (adolescents) and EU (2 months – Most advanced in development adolescents old and above) – Phase III start in 2017 – Approved in 64 countries – ACIP category B (permissive) recommendation – US filing expected in 2020 – 2015 sales (Mar – Sept): £135m – Approved in 38 countries – 2015 sales (Mar – Sept): £78m
Meningitis portfolio expected to contribute ~1/3 of 2020 sales growth targets for GSK vaccines
67 Bexsero: multi-component antigen composition adds value, differentiation
Bexsero – 4 antigens composition – 2 dose regimen
100 80 60 40 20 0
Strain 1 Strain 2 Strain 3 Strain 4* % subjects with bactericidal activitybactericidal with subjects% Baseline 1m Post Dose 1 1m Post Dose 2
Sources: Santolaya et al. Hum Vac & Imm 2013 http://goo.gl/8oWB4P; * Strain 4 GSK data on file. Post hoc assays on a subset 68 Competing vaccine for MenB
Competing vaccine – 1 antigen composition with 2 variants – 3 dose regimen
100 80 60 40 20 0
Strain 1 Strain 2 Strain 3 Strain 4 % subjects with bactericidal activitybactericidal with subjects% Baseline 1m Post Dose 1 1m Post Dose 2 1m Post Dose 3
ClinTrial.gov, study NCT01299480 https://goo.gl/Eqbmph 69 Slide intentionally blank
70 Slide intentionally blank
71 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 – Filing expected 2020 for adolescents (~80% (~29% schedule penetration) penetration) previously immunised for MenACWY
Post dose 2 immune response rate MenB Bexsero or Bexsero or Other MenB Other MenB 100 additions Other MenB 99 100 97 100 99 93 80 3-4 injections 64
60 62 ≥threshold
40
titer
MenABCWY 20
% of subjects with with subjectsof % combination MenACWY MenABCWY Bexsero hSBA 0 planned
MenB 2 injections
Saez-Llorens X et al. Hum Vacc Imm 2015 http://goo.gl/PXXRs6; GSK data on file. CDC MMWR: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6429a3.htm#tab1 72 Meningitis portfolio presents significant opportunity
GSK has most advanced and comprehensive portfolio for meningitis vaccines
2017 2018 2019 2020 Bexsero demonstrated significant public health benefit, could drive further UMV recommendations
Combination approach is optimal option for prevention MenABCWY Bexsero MenABCWY Phase III start US/UK US filing paediatric data Bexsero capacity ~25m doses in 2018
73 Respiratory Syncytial Virus (RSV) Period of most severe RSV cases for young infants occurs from birth to 12 months
35,000
30,000
25,000
20,000 15,000 Hospitalisations
10,000 US US
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 Period of most severe RSV cases for young infants occurs from birth to 12 months
35,000 Maternal Vaccine Paediatric Vaccine 30,000
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 Hospitalisations
10,000 US US Maternal IgG 5,000 Infant’s immune response Period of greatest Risk for severe 0 RSV disease 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 76 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
core 6-11 mos principle 2021 2022
Completed Planned
Double stranded DNA Target RSV genes
77 Novel candidate RSV maternal vaccine approach
Absorbtion with Pre-F but not Post-F depletes neutralising SiteSite II IgG from convalescent serum For RSV F protein, the SiteSite IV IV SiteSite ØØ correct antigen structure 100 SiteSite IIII is critical SiteSite IIII 90 80 Pre-F absorbs out 70 neutralising RSV 60 antibodies more than 10x 50 Site IV better than Post-F and 40 induces potent antibody 30 20 responses in humans LOD 10
Pre-F Post-F % neutralising antibody absorbed antibody neutralising %
Graham B et al., Current Opinion in Immunology 35; 30-38, 2015 Post-F Pre-F GSK preclinical data, unpublished
78 Stabilised Pre-F generated high titers by Day 7 and potent boost of PCA without adjuvant
GSK Pre-F
2048 25
20 Titer
1024
Ab 15 512 10 256
PCA Fold increase 5 Neutralising 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, unpublished 79 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
20 20
Titer Titer
1024
1024
Ab Ab 15 15
512 512
10 10 256 256
Fold increase PCA Fold increase 5 Fold increase PCA Fold increase 5
Neutralising Neutralising 128 0 128 0 60 plain 60 plain 60 plain 60 Al 120 Al Day 30 Day 30 Day 0 Day 7 Day 30 Day 0 Day 7 Day 30
>20 fold PCA increase after single dose without adjuvant >10 fold PCA increase requires 120 ug + adjuvant
Glenn GM, J Infect Dis. 2015 Aug 10. pii: jiv406. [Epub ahead of print] (data on 60 ug with/without alum) GSK internal data, unpublished Presentation by Novavax at World Vaccine Congress April 2015 (data on 120 ug/alum dose PCA) 80 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 Group B Streptococcus (GBS) Maternal immunisation for GBS
The leading No GBS disease GBS disease 40 cause of pneumonia, meningitis and sepsis in 35
neonates 30
25 1 in 2500 of babies
develop GBS disease 20 infants infants despite antibiotic
% 15
prophylaxis of colonised mothers 10
5
No vaccine is available
0
.99
<20
-
5.99 1.99 2.99 3.99 4.99 6.99 7.99 8.99 9.99
<0.5
------
14.99 19.99
- -
5 1 2 3 4 6 7 8 9
<0.5
10 15 Maternal antibody concentration
Gibbs, Obstet Gynecol, 104;1062-1075, 2004 Lin FY et al. J Infect Dis. 2004;190:928-934 83 Maternal immunisation for GBS
The leading No GBS disease GBS disease 40 cause of pneumonia,
meningitis and sepsis in 35
neonates 30
25 1 in 2500 of babies
develop GBS disease 20 Protected infants infants despite antibiotic
% 15
prophylaxis of colonised mothers 10
5
No vaccine is available
0
.99
<20
-
5.99 1.99 2.99 3.99 4.99 6.99 7.99 8.99 9.99
<0.5
------
14.99 19.99
- -
5 1 2 3 4 6 7 8 9
<0.5
10 15 Maternal antibody concentration
Gibbs, Obstet Gynecol, 104;1062-1075, 2004 Lin FY et al. J Infect Dis. 2004;190:928-934 84 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 protein carrier Capsular polysaccharide 5 dominant from GBS serotypes Designed to help protect against >95% of 25
Vaccinated mothers ) globally prevalent Infants of vaccinated mothers mL 20 Unvaccinated mothers and their infants serotypes
15 Phase II trivalent 2014 2015 2016 2017 2018 2019 10 vaccine antibody data shows response at 5
Phase II Validation of 1gG againstserotypes(µg/ 1gG1a Trivalent Assay development protective Further development period of greatest risk 0 Pre Delivery Birth Day 42 Day 90 Completed antibody threshold EOD LOD Period of greatest risk disease for GBS
Le Doare, Vaccine 31(4) D7, 2013 ; GSK clinical data, unpublished 85 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
Placebo with
Flu vaccine
Proportion Proportion
onfirmed influenza onfirmed
c –
– 0.00 0 2 4 6 Age (months)
Source: N Engl J Med. 2014 Sep 4;371(10):918-31 86 GSK potential maternal immunisation vaccine portfolio
Pertussis GBS
50%
45% 40%
35%
30% 25% 20% Influenza cases of Percent RSV 15% 10%
5%
0% 0-7d 8-30d 30-90d >90d Winter K, MMWR 63:1122- Age of onset
1140,2014 Melin, Clin Microbiol Inf, Associated Mortality
- 17;1294-1303, 2011 (deaths (deaths per 100,000 children) Influenza
<6 m 6-11m 1 yr 2 yr 3 yr 4yr 5-10yr 11-17yr
Age Group
Bhat N Engl J Med.353:2559-67, 2005 Paramore, Pharmacoeconomics 22:274-285, 2004
87 A new vaccine concept 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 – exacerbations1,2 NTHi 001 NTHi 003 NTHi 004 NTHiMcat Adults with Healthy Adults Older adult Adults with smokers GOLD III/IV 75% effective vaccine could eliminate 20- GOLD II/III COPD 35% of exacerbations COPD
NTHiMcat 001 Proof of concept End 2019 Healthy Adults Proof of 3 antigen vaccine covering NTHi using AS01 Completed principle End 2017 adjuvant in Phase II POC trial Ongoing Planned Safety and immuno data end 2016 Key POC data in COPD patients = 2017
Phase III to be defined based on POC data
1GSK unpublished data EpiHip001. 2Sethi et al. N Engl J Med. 2002 Aug 15;347(7):465-71. 89 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 compromised US filing paediatric data US filing filings efficacy filing
Shingrix US, EU, MMR Japan Rotarix liquid GBS maternal Japan filings filing US filing filings
RSV paediatric filings
COPD vaccine Phase III
90 R&D programmes to deliver near-term growth with significant future opportunities and novel immunisation platforms
A new vaccine concept 3 − COPD
Longer term R&D Focus − RSV 2 − GBS
Near/mid term key R&D focus: − Shingrix 1 − Meningitis − Lifecycle management
91 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 Centre
92 Q&A Immuno-Inflammation 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 - 100 out of • Mechanisms are relevant for countries1 countries; largest proportion 100,000 4; 9/10 sufferers are mainstream diseases e.g of musculoskeletal women in their 20s & 30s4 psoriasis, Crohn’s disease & • Aging demographics a major diseases2,3 ulcerative colitis driver of market growth • Chronic disease with poor QoL, • Aging demographics a major involving musculoskeletal, • Opportunities exist to treat • Highly debilitating; associated driver of market growth haematological, cutaneous & less common disease e.g. with higher mortality & renal systems primary Sjögren's syndrome, progression to other serious • Major opportunity for a • Mortality rate 3x higher than the systemic sclerosis & conditions disease-modifying therapy general population, and 10x myasthenia gravis • Significant medical needs for • Immune modulation offers higher in under 405 remission-inducing therapies & opportunity to move from • Benlysta IV - 1st drug approved for patients resistant to current only alleviating symptoms of for SLE in 50 years (2011) standard of care “wear and tear”
1 Decision Base Rheumatoid Arthritis 2015 ; 2 World Health Organisation 2010; 3 Decision Resources OA Pain 2012; 4 Danchenko N et al. Epidemiology of SLE: a comparison of worldwide disease burden. Lupus 2006; 15:308–318 5 Bernatsky S, Boivin JF, Joseph L, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum 2006; 54:2550–2557.; * Decision resources 2013 estimate 95 Immuno-Inflammation R&D strategy: From symptomatic benefit to sustainable remission
macrophage
Targeted Biologicals Targeted Small neutrophil Molecules
stromal cell
Targeting Resistant Early Intervention &
T cell Disease Remission Induction GSK Pipeline GSK
plasma cell
B cell 96 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) 80 ** ** p < 0.05 57 63 60 • Targets the cytokine ** ** 40 30 27 27 • Efficacy demonstrated in Phase II; consistent 20 3 safety profile across doses (%) rate Response 0 ACR20 at wk 12 ACR50 at wk 12 (Primary EP) • >3000 patients in studies to date placebo 50mg Q4W 100mg Q2W 1adapted from Smolen et al 2014 Ann Rheum Dis 73 (9) • Phase III interim read-out, full read out expected by year end 2015 24 w data from Japan monotherapy study2
82 74 • Indication expansion: Phase III in Giant Cell 80 64 60 49 Arteritis started screening. Phase II in asthma 36 40 25 start in 2016 20
Response rate (%) rate Response 0 Status: RA: Phase III ACR20 ACR50 ACR70 Indications: RA (lead), GCA, asthma 50mg Q4W 100mg Q2W Planned Filing: RA 2016 2 ACR 2015 abstract #1672 97 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
• Reduction in macrophage infiltration correlates with improvement in disease activity scores1,2
• Macrophage is a primary cause of tissue destruction and affects many other cell types
• GM-CSF is important in every step of macrophage production and infiltration in the tissues
1 Boumans MJ, et al. Arthritis Rheum. 2011;63:3187-94. 2 Bresnihan B, et al. J Rheumatol 2009;36:1800-2. 98 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 80 Phase Ib/IIa study, N= 96 action and long duration post treatment
• Effect size appears similar or greater than 60 anti-TNF 40 • Targeting the macrophage in early RA 20
• Potential for early use to induce remission response EULAR %
• BAROQUE (RA Phase IIb) ongoing. 0 Placebo 0.3 mg/kg 1.0 mg/kg 1.5 mg/kg Initial clinical read-out 2016
Week 4 Week 6 Week 8 Status: Phase IIb Indication: Rheumatoid Arthritis Planned Filing: 2021-2025 Behrens, et al. Ann Rheum Dis. 2015;74:1058-64
99 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 of OA
• aGM-CSF rapidly reduces pain (through effect on nerves) in animal models of OA
• Hand OA presents unique clinical development path M Schweizerhof et al. Nature Medicine 2009;15:802-807 Pain • Phase II to start in 2016 110
* * * # * * * * 100 * * * * * anti-GM-CSF * p<0.05,
** p<0.01, 90 control *** p<0.001, control vs. anti-GM CSF # 80 p<0.0001, control and anti- Status: Phase II start 2016 distribution Weight GM-CSF vs. t=0 readings Indication: Hand OA 70 Planned Filing: 2021-2025 0 5 10 15 20 25 30 35 40 45 Days post disease induction Cook et al. Arthritis Res Ther. 2012;14:R199 GSK3196165 in-licensed from MorphoSys AG 100
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 Kinome plot RIP1 kinase inhibition
• World leading internal team achieved in the clinic
• Anti-TNF effect with additional 250
protection against effects of cell 200 activity death 150 100 IC50=2 nM
• GSK2982772 well tolerated at all kinase 50 doses with robust target inhibition 0 achieved RIP1 0.1 1 10 100 1000 GSK2982772 -most selective ATP Blood levels (ng/mL) • Exquisite kinase selectivity competitive kinase inhibitor to advance into man • Multiple potential indications Authors: Yves Dondelinger, Sandrine Molecular Cell Jouan-Lanhouet, Tatyana Divert, Emilie “NF-B-Independent Role of IKK/IKK in Preventing Theatre, John Bertin, Peter J. Cough, RIPK1 Kinase-Dependent Apoptotic and Necroptotic Piero Giansanti, Albert J.R. Heck, Status: Phase I Cell Death during TNF Signaling” Emmanuel Dejardin, Peter Vandenabeele, Indications: Rheumatoid arthritis, Mathieu J.M. Bertrand Psoriasis, Ulcerative Colitis 1Ofengeim & Yuan. Nat Rev Mol Cell Biol. 2013;14:727-36 Planned Filing: 2021-2025 101 GSK2982772: studies in three indications to start in 2016 Key target, compelling target, compelling pre-clinical data
* 100 Three Phase II
80 RIP1 status Clinical Studies Blocks severe clinical studies to 60 wt/wt 1 skin inflammation progress in parallel 40 wt/K45A K45A/K45A dermatitis mid-2016 20 % without severe without % * 0 0 50 100 150 200 250 rheumatoid arthritis Time (days) 0 C) Plans in place to o -2 rapidly deliver Prevents against -4 clinical validation in TNF induced shock1 -6 2017 -8 ulcerative colitis Temperature ( Temperature -10 ∆ ∆ 0 2 4 6 Time (hr)
120
100 Filing: 2021 - 2025
80 psoriasis release
Inhibits TNF production 60 in human gut from (% control) control) (%
TNFa 40 2 20 Crohn’s
0 1 Ctrl Pred 300 30 3 Berger et al. J Immunol. 2014;192:5476-80 2GSK, data on file. 1mM RIP1i (nM) 102 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
p=0.0011 • Improvement in time to first severe flare (HR 0.5 80 p< 0.0003) – flare is the major driver of disease 60.8% progression. 60 48.4% • Trend for reduction in corticosteroid use seen again (p=0.07). Further evaluation ongoing. 40 135/279 158/246 • Subcutaneous weekly medicine. 20 • 9 ongoing studies, including subgroups in SLE and other indications. 0 All patients
Status: IV approved 2011 Indication: SLE Placebo belimumab-SC 200 mg Planned Filing: SC file Q4 2015/Q1 2016 ACR 2015 -abstract #3218 103 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 • Severe, refractory Sjögren's syndrome, mL re-population with auto-immune / parotid B-cell lymphoma and
ng 20
B-cells cryoglobulinaemic vasculitis
10 • Failed several immunosuppressants, • Benlysta suppresses BLyS plasma exchange & surgical therapy as
Serum BLyS ( BLyS Serum well as Benlysta alone and rituximab 0 • Single patient case report Pre Post alone suggests complete and Rituximab • Dramatic response to combination persistent response in patient including complete and persistent treated with aCD20 + Benlysta regression of lymphoma
104 Early Immuno-Inflammation clinical phase pipeline with multiple first in class assets
Phase I – GSK525762 (BET) • Multiple first in class assets GSK2982772 (RIP1) • Eight key disease mechanisms GSK3050002 * † (aCCL20) • Four biologicals GSK2831781 * † (aLAG3) • Smart clinical development GSK2618960 * programmes to get early data read-outs (aIL7R) GSK2330811 * (aOSM) GSK2646264 (Syk topical) Potential first in class
GSK3117391 * Biopharmaceutical (ESM -HDAC) † Collaboration with third party 105 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 IL-7R 14 C Sjögren’s syndrome 10
• IL-7R inhibition affects 6 pathogenic T cell survival, 6
reducing cytokine and auto- patient
antibody production • IL-7 promotes Sjӧgren’s-like syndrome in animal models1 4
CD3 T cells T CD3
• Potential for disease modification α G IL-7R
by prevention of salivary and 7R
- IL
lacrimal gland destruction 2
• Phase I study in healthy of total numbers) LSG cell (% volunteers completed - well
tolerated control Status: Phase II start 2016 0 Controls Patients Planned Filing: 2021-2025 N=10 n=13 • represents outlier Bikker et al. Ann Rheum Dis. 2012;71:1027-33. 1. Jin et al. Arthritis.Rhematol. 2013;65:2132-2142 106 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 “First in class” treatment for CCR6 pos T cells (%) in blister model psoriatic arthritis • Unique MOA - CCL20 inhibition 0 baseline blocks recruitment of pathogenic immune cells - -10 single receptor • Potential to perturb chronic -20 inflammation & reduce disease activity – applicability in mean ± SD multiple diseases -30 GSK3050002 (n=6) • Inhibits CCR6+ T cells placebo (n=12) migration into inflamed tissue in baselinefrom change Mean -40 humans in vivo placebo 0.1 0.5 1 5 10 20 mg/kg GSK3050002
Status: Phase II start 2016 GSK, data on file. GSK3050002 in experimental medicine study (200784) Planned Filing: 2021-2025 • Selective inhibition (CCR6 +ve cells only) • Dose dependency 107 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 driven II indications • Unique MOA – a-LAG3 depletes recently activated, Depletion of LAG- “pathogenic” T cells 3 T-cells at • Potential for long term disease challenge site ... remission in multiple T cell- driven indications
15.0 2000 UI PPD 12.5
(mm) 40 UI PPD 10.0
ch A9H12 ..results in 7.5 0.1 mg/Kg suppression in 2.5 the skin reaction
Erythema 2.5 Status: Phase I ongoing 0.0 3 weeks
Planned Filing: 2021-2025 0 2 4 6 8 days 0 2 4 6 8 days IDR 1 IDR 2 Poirier et al. Clin Exp Immunol. 2011;164:265-74. 108 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 systemic sclerosis 8 • Systemic sclerosis patients have increased OSM serum levels and upregulated OSM and OSM-related genes in skin 6 biopsies (data at ACR)
• Inhibition of OSM signalling is expected to reduce 4 inflammation, vascular dysregulation and fibrosis 2
Average number of infiltratesofnumber Average
0
0 Healthy Diffuse cutaneous Status: Phase I ongoing controls systemic sclerosis Planned Filing: 2021-2025 ACR 2015, abstract #1914
109 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” treatment for “First in class” treatment for T- “First in class” treatment for Sjögren’s syndrome psoriatic arthritis cell driven II indications systemic sclerosis • IL-7R inhibition affects • Unique MOA - CCL20 inhibition • Unique MOA – a-LAG3 • Systemic sclerosis patients pathogenic T cell survival, blocks recruitment of depletes recently activated, have increased OSM serum reducing cytokine and auto- pathogenic immune cells - “pathogenic” T cells levels and upregulated OSM antibody production single receptor and OSM-related genes in skin • Potential for long term disease • Potential to perturb chronic biopsies (data at ACR) • IL-7 promotes Sjӧgren’s remission in multiple T cell- inflammation & reduce disease syndrome in animal models driven indications • Inhibition of OSM signalling is activity – applicability in expected to reduce • Potential for disease modification multiple diseases inflammation, vascular by prevention of salivary and • Inhibits CCR6+ T cells dysregulation and fibrosis lacrimal gland destruction migration into inflamed tissue in • Phase I study in healthy humans in vivo volunteers completed - well tolerated
Status: Phase II start 2016 Status: Phase II start 2016 Status: Phase I ongoing Status: Phase I ongoing Planned Filing: 2021-2025 Planned Filing: 2021-2025 Planned Filing: 2021-2025 Planned Filing: 2021-2025
110 Immuno-Inflammation R&D strategy: From symptomatic benefit to sustainable remission
macrophage
Targeted Biologicals Targeted Small Molecules neutrophil
• Benlysta
• sirukumab • RIP1 • Anti-GM-CSF • I-BET stromal cell • Anti-IL-7 • Anti-LAG3 • Anti-CCL20 • Anti-OSM
Targeting Resistant Early Intervention & T cell Disease Remission Induction
GSK PipelineGSK • RIP1 • Anti-GM-CSF • I-BET • RIP1 plasma cell • Anti-IL-7 • Anti-LAG3 • Anti-CCL20 • Anti-CCL20 • Anti-OSM • Anti-LAG3
B cell
111 Oncology Oncology R&D strategy Focusing on 3 areas fundamental to oncology
Cancer Epigenetics Long-Term Survival & Reprogram Cancer Cures Cells
Immuno-Oncology Stimulate Anti -Tumour First in Class Medicines
Immunity & Combination Therapy GSK Pipeline GSK
Cancer Stem Cells
113 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 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 activity in preclinical cell line models • PoC opportunity in NUT midline carcinoma (NMC) • Rare and rapidly lethal cancer caused by chromosomal translocation involving BET target (NUT gene and either BRD3, BRD4, or NSD3 (which binds BRD4) gene) Nature 2010;468:1119-1123 100
10
1 gIC50, µM gIC50, 0.1
Status: Phase I 0.01 Indications: Solid Tumours, Heme Malignancies Filing: 2018 0.001 Preclinical data show activity of GSK525762 in many cancer types (gIC50 < 1 mM) 115 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 underway across multiple tumour types; – 36 patients enrolled across CRC, NMC, CRPC, SCLC, BC & MM
• Haematological studies underway; partial responses seen in AML – 20 patients enrolled cross AML, NHL & MM
Chest CT of patient with NMC treated with GSK525762: ~ 90 % reduction in tumour volume at week 16 GSK, data on file. 116 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/kg day 0-20 GSK1210151A 10 mg/kg p.o. day 0-10 • Profound cytokine, chemokine and immunoglobulin 6 inhibition in human macrophages1 and RA patient samples and biopsies 4 1 2 2
• Modulation of macrophage , osteoclast and Th17 cell Clinical score types 0 Sensitisation0 5 boost 10 15 20 25 • Profound inhibition of disease in multiple RA preclinical Day (post sensitisation) models2 250% I-BET inhibition of RA stromal
• Rebalances gene expression in RA stromal cells alone
cell activation – gene expression profile
1 200%
(decreased cytokines, chemokines, metalloproteases, - * elevated protease inhibitors3, 4 * * 150%
1.Chan et al. 2014 EJ Imm., 2. Park-Min et al. 2014 NatCom, 3. Xiao et al. 2015 Rheumatology, 4. Klein et al. 2014 ARD 100% * * * * * * 50% * * Status: Phase II start 2016 * * * * * * Expression relative to IL relative Expression * * * * * * * * *
Indication: Therapy Resistant RA * *
0%
Planned Filing: 2021-2025
IL6 IL8
TNF
FGF2 SELE
CSF3
CD44 CCL2
TGFA
BMP2
EREG
IFNB1
MMP7 MMP8 MMP3 MMP1
TIMP1
ICAM1
FGF13
CXCL5 CXCL2 CXCL3 CXCL6 CXCL9
VEGFA
VCAM1 MMP10 MMP13 MMP12 CXCL11 CXCL10 117 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 significant progression-free survival PD PD for some patients PD
Untreated 10 nM GSK552 PD PD PD PD
PD Study number Study PD SD SD SD SD
SD MLL-AF9 mouse derived leukemia 40 140 240 340 440 540 cells treated for 6 days in vitro Treatment duration (days) Status: Phase I Best confirmed response –PR: Partial Response, SD: Stable Disease, PD: Indications: AML, SCLC Progressive Disease, NE: Not Evaluable Planned Filing: 2020 Triangles indicate ongoing subjects GSK, data on file. 118 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 combination 60 Sarcoma Phase I/II: Best Response in treated patients (N=12)*
with checkpoint modulators 40 Best response Stable disease Confirmed complete or partial response 20 17 15
• Collaboration with Adaptimmune 0 -20 -15 -16 -26 -40
baseline (%) baseline -50 Status: Phase I/II -60 -55 -58 -64 Indications: NY-ESO-1 positive Cancers: -80 -70 Excludes 3 subjects who did not receive a T-Cell Infusion.
Sarcoma, Myeloma, NSCLC, targetinChangelesion from -100 Melanoma, Ovarian Cancer One subject with disease progression is excluded because lesion could not be measured -100 *Subjects did not receive the target cell dose Filing strategy to be agreed with Adaptimmune -120 261* 230 206* 207 200 204 202 209 205 208 201 Subject number Note: GSK3377794 subject to exercise of option by GSK GSK, data on file. 119 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 80 • Dual mechanism: enhancing effector T-cell and 60 aOX40 /aPD-1 suppressing T-regs 40
20 aOX40 Percent survival Percent control aPD-1 • Phase I Study started in eight cancers 0 20 30 40 50 60 70 80 90 Time (days) • Combination with Merck PD1 in 2016 Survival in animal model (CT26) OX-40 + TLR-4 100 • Combination with GSK TLR4 in 2017 TLR4a / aOX40 • Collaboration with MD Anderson 50
TLR4a Percent survival Percent Status: Phase I control aOX40 Indications: Solid tumours, Heme Malignancies 0 Planned Filing: 2020 0 50 100 150 Study day GSK, data on file. 120 Immuno-Oncology: GSK3359609 first-in-class ICOS agonist antibody
• Universal mechanism across ICOS in ipilimumab-treated patients GSK3359609 multiple cancers CD4 ICOS T cells
80 T cell Activation in-vitro
L 100 CD69+ CD4 T cells 24hr after stimulation • Patient selection biomarker m 60 80 40 • Enhances T-cells associated with 60 20 40 survival count/ Cell 0 20 Baseline W7 W12 W24 0 • Use after CTLA-4 and PD-1 in Ipilimumab Responders T CD4 cellsof total % 0.01 0.1 1 10 100 Ipilimumab Non-Responders unresponsive or refractory patients ICOS Ab (ug/ml) CD4 ICOS T cells T cell Proliferation in-vitro • Possible anchor for use in 100 25 Ki67+ CD4 T cells 48hr after stimulation 80 combinations CD4 ICOS >4 20 60 15 40 • Collaboration with INSERM (%) OS 20 10 CD4 ICOS ≤4 0 5 Status: Phase I start Q1 2016 0 12 24 36 48 60
% of total CD4 T T CD4 cellsof total % 0 Indications: Solid tumours, Heme Malignancies Time (months) 0.01 0.1 1 10 100 Planned Filing: 2020 ICOS Ab (ug/ml) DiGiacomo, Clin Immunol Immunother 2013 121 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% * # 30 * * # • Ongoing randomised Phase II * 10 studies in pancreatic cancer and * # * * * * * * *
SCLC -10 -30 • Phase II read-out 2016 -50 • Collaboration with OncoMed 5 mg/kg +Nab-P+ gem 12.5 mg/kg +Nab-P+ gem * :NOTCH3 high (>50%) -70 7.5 mg/kg +Nab-P+ gem 15 mg/kg +Nab-P+ gem # NOTCH3 data not available
Tumour volume reduction baseline reduction from volume Tumour 10 mg/kg +Nab-P+ gem
Attractive signal over 23% ORR of Gem/Abraxane SOC in hard-to-treat cancer
Status: Phase II O’Reilly et al. 2015 Gastrointestinal Cancer Symposium Indications: Pancreatic cancer and Small Cell Lung Cancer Note: tarextumab subject to exercise of option by GSK Planned Filing: 2020 *Abraxane is a trademark of Abraxis Bioscience LLC 122 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 • Immuno-oncology Immuno-Oncology • Stem cells • NY-ESO-1 TCR-T • OX40 agonist (GSK3174998) Stimulate Anti -tumour First in Class Medicines • ICOS agonist Immunity & Combination Therapy • TLR4 agonist Pipeline GSK • Immuno-oncology • Epigenetics • Immuno-oncology Cancer Stem Cells • Stem cells
• Notch2/3 (tarextumab) • Notch1 (brontictuzumab)
123 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 molecule targets (X6)
NY-ESO-1 TCR-T † Sarcoma, Multiple Myeloma, NSCLC, Ovarian, Melanoma OX40 agonist (GSK3174998) † Solid tumours, Heme Malignancies † ICOS agonist (GSK3359609) Epigenetics TLR4 agonist (GSK1795091) Immuno-Oncology CAR-T and TCR-T targets (x6) Novel small molecule targets (x2) Stem Cells † ImmTacs (x4) Other targeted therapies mAb-dAbs and dual-specific Abs (x5)
Notch2/3 (tarextumab) † Pancreatic, SCLC Notch1 (brontictuzumab) † Solid tumours, Heme Malignancies
BCMA ADC (GSK2857916) Multiple Myeloma † Collaboration with a third party. FGF Ligand Trap (GSK3052230) † Mesothelioma, NSCLC 124 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 (mepolizumab) IL-6 mAb IL-5 mAb Notch 2/3 mAb GSK2315698 IL-6 mAb Alpha V beta 6 BET inhibitor GM-CSF mAb IL-5 mAb SAP mAb + SAP integrin Rheumatoid Nasal Pancreatic depleter antagonist Therapy HIV / Severe Asthma Arthritis Polyposis Cancer, SCLC Amyloidosis Severe Asthma IPF Resistant RA RA, OA Infectious Diseases mepolizumab GSK2696273 mepolizumab GSK525762 GSK2998728† danirixin Long acting IL-5 GSK2330811 GSK2696277†^ IL-5 mAb Ex-vivo stem CGT IL-5 mAb BET inhibitor TTR production CXCR2 mAb (NBE) OSM mAb Ex-vivo stem CGT Solid Tumours, inhibitor antagonist Immuno-Inflammation Haematological TTR Systemic Beta COPD ADA-SCID HES Malignancies Cardiomyopathy COPD Asthma, Others Sclerosis Thalassemia Oncology mepolizumab GSK2696274 dolutegravir + GSK2879552 daprodustat* GSK2269557 IL5/13 bispecific GSK2618960 daprodustat* IL-5 mAb Ex-vivo stem CGT lamivudine FDC LSD1 inhibitor Prolyl PI3 kinase delta antibody IL-7 receptor Prolyl Integrase Acute Myeloid hydroxylase inhibitor mAb hydroxylase Metachromatic inhibitor+NRTI Leukaemia, inhibitor Sjogren’s inhibitor (topical) Rare Diseases EGPA Leukodystrophy HIV SCLC Anaemia of CKD COPD, Asthma Asthma Syndrome Wound Healing
fluticasone GSK2696275 cabotegravir GSK3174998 GSK2862277 GSK2878175 GSK2831781 mepolizumab furoate+vilanterol Ex-vivo stem CGT Long acting OX40 agonist mAb TNFR1 dAb NS5B inhibitor LAG-3 mAb IL-5 mAb Other +umeclidinium integrase Solid tumours, ICS/LABA/LAMA Wiscott-Aldrich inhibitor Haematological Acute Lung Autoimmune Severe Atopic COPD Syndrome HIV, HIV PrEP Malignancies Injury HCV Diseases Dermatitis
dolutegravir + GSK2998728† gepotidacin GSK3377794† # GSK2245035 GSK3228836† GSK2982772 rilpivirine TTR production Type 2 NY-ESO-1 TCR TLR7 agonist Antisense RIP1 kinase inhibitor Integrase inhibitor topoisomerase Sarcoma, Mult. oligonucleotide inhibitor † + NNRTI inhibitor Myel., Melanoma Psoriasis, RA, Subject to exercise of option HIV FAP Bacterial Inf. Ovarian, NSCLC Asthma HBV UC # Subject to collaborator agreement
Benlysta sirukumab GSK3359609 GSK3191812 belimumab + GSK3050002 ^ EU filing Subcutaneous IL-6 mAb ICOS agonist mAb TSLP dAb CD20 CCL20 mAb * USAN, INN approval pending BLyS mAb Solid tumours, BLyS+CD20 Giant Cell Haematological Sjogren’s Psoriatic SLE Arteritis Malignancies Asthma Syndrome Arthritis 125 Rare Diseases Amyloidosis and Cell and Gene Therapy 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 caused by wild type TTR (senile amyloidosis) • AA amyloidosis – complication of chronic inflammation or infection • Implication in other disease states. Growing recognition of its importance
Accumulation of amyloid deposits damages vital organs causing disease Peripheral / visceral nerves Kidney Heart Liver
TTR AA, AL, TTR AL, TTR AL, AA
127 Two fundamental approaches to treatment: prevent amyloid formation and remove amyloid deposits
“Gene silencing” by antisense oligonucleotide Removal of amyloid deposits by macrophage-mediated clearance –DNA –mRNA –Protein Serum amyloid P component (SAP) in blood and all amyloid –Antisense Oligo deposits
SAP removed from plasma by –RNase H GSK SAP depleter but still decorates deposits in organs
Anti-SAP mAb can then target SAP in amyloid deposits • Knockdown of TTR gene prevents production of mutant and wild type TTR protein Antibody binding triggers amyloid • Prevents formation of amyloid deposits in vital organs clearance by macrophages
• GSK2998728 in collaboration with Isis Pharmaceuticals Organ function is restored
128 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%
placebo 50 mg 100 mg 200 mg 300 mg 400 mg Max TTR reduction = 92%
SEM) 30 - 25 10
20 -10
)
dL -30 15 SEM) 76%
± reduction -50 10
(mg/ TTR
( Mean -70
Treatment period 5 -90 lower limit Transthyretin (mean % Chg +/ Chg % (mean Transthyretin BL 8 15 22 29 36 43 50 57 64 71 78 85 92 of quantitation Study day 0 Phase 3 Phase 3 FAP OLE Status: Phase III FAP ≥ 3 months (nadir) Indication: Familial amyloid polyneuropathy (FAP); Baseline n = 38 Familial and wild-type amyloid cardiomyopathy (TTR CM) GSK: data on file Filing: 2017 (FAP), 2020 (TTR CM) Note: GSK2998728 is a collaboration with Isis Pharmaceuticals Ackermann et al. International Symposium on Amyloidosis. 2012, poster #0P73 and subject to exercise of option by GSK 129 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 anti-SAP • US breakthrough status application planned • Use in cardiac AL and ATTR amyloidosis • Example of academic partnership model • Collaboration with Pentraxin
Liver ECV (median normal 29%) 36.0 29.0 Liver Stiffness (median normal 5.3 kPa) 5.7 2.8 % of tracer in liver 61.1 17.4 Therapeutic clearance of amyloid by antibodies to serum amyloid P component
Richards et al. N Engl J Med 2015; 373:1106-1114 130 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 medically important disease states antisense amyloid deposits oligonucleotide by macrophage- • GSK approaches address both removal mediated clearance of existing deposits and prevention of TTR to prevent Anti-SAP mAb to target accumulation formation of amyloid SAP in amyloid deposits deposits in vital organs • World class expertise – ability to maximise the opportunity from our leadership position – Oral SAP depleter/ anti fibril approaches
131 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
infections • Fatal 0.80 • Life-threatening opportunistic 0.60
infections 0.40
0.20
Status: Filed in Europe 0.00 Indication: ADA SCID Planned Filing: US filing 2017 Time period GSK2696273 is a collaboration with Telethon and Ospedale San Raffaele Cicalese et al. ESID 2015, poster #0779. 132 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 a Leukodystrophy Wiskott-Aldrich Syndrome (WAS) • Beta thalassaemia study started • Thrombocytopenia Wiskott-Aldrich • Infections a Syndrome • Autoimmune disease • Building GSK platform capability in • Lymphoma cell and gene therapy. New Beta thalassemia b alliances and internal platform build MPS1 b
• Cell gene therapy approaches in Chronic Granulomatous disease b oncology and potentially other Metachromatic areas. IP estate and know-how Globoid Cell Leukodystrophy (MLD) Leukodystrophy b • Fatal accumulating • Rapid loss in cognitive & motor a Licensed from Telethon and Ospedale San Raffaele function, followed by death b GSK holds an option to license programme from Telethon and Ospedale San Raffaele 133 Cell Gene Therapy clinical effect in MLD
Motor function by GMFM in LI patients 100
80
60
40
GMFM score (%) score GMFM 20
0 0 20 40 60 80 100 120 Chronological age (months) Biffi et al. ESCGT 2015 presentation 134 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 Unit Physician II Receptor DPU
Axel Hoos Chris Carpenter Vice President, Head Vice President, Head of Immuno-Oncology Cancer Epigenetics DPU
Duncan Richards Sven Kili Vice President, Head Academic Vice President, Development DPU Head for Gene Therapy
135 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 (mepolizumab) IL-6 mAb IL-5 mAb Notch 2/3 mAb GSK2315698 IL-6 mAb Alpha V beta 6 BET inhibitor GM-CSF mAb IL-5 mAb SAP mAb + SAP integrin Rheumatoid Nasal Pancreatic depleter antagonist Therapy HIV / Severe Asthma Arthritis Polyposis Cancer, SCLC Amyloidosis Severe Asthma IPF Resistant RA RA, OA Infectious Diseases mepolizumab GSK2696273 mepolizumab GSK525762 GSK2998728† danirixin Long acting IL-5 GSK2330811 GSK2696277†^ IL-5 mAb Ex-vivo stem CGT IL-5 mAb BET inhibitor TTR production CXCR2 mAb (NBE) OSM mAb Ex-vivo stem CGT Solid Tumours, inhibitor antagonist Immuno-Inflammation Haematological TTR Systemic Beta COPD ADA-SCID HES Malignancies Cardiomyopathy COPD Asthma, Others Sclerosis Thalassemia Oncology mepolizumab GSK2696274 dolutegravir + GSK2879552 daprodustat* GSK2269557 IL5/13 bispecific GSK2618960 daprodustat* IL-5 mAb Ex-vivo stem CGT lamivudine FDC LSD1 inhibitor Prolyl PI3 kinase delta antibody IL-7 receptor Prolyl Integrase Acute Myeloid hydroxylase inhibitor mAb hydroxylase Metachromatic inhibitor+NRTI Leukaemia, inhibitor Sjogren’s inhibitor (topical) Rare Diseases EGPA Leukodystrophy HIV SCLC Anaemia of CKD COPD, Asthma Asthma Syndrome Wound Healing
fluticasone GSK2696275 cabotegravir GSK3174998 GSK2862277 GSK2878175 GSK2831781 mepolizumab furoate+vilanterol Ex-vivo stem CGT Long acting OX40 agonist mAb TNFR1 dAb NS5B inhibitor LAG-3 mAb IL-5 mAb Other +umeclidinium integrase Solid tumours, ICS/LABA/LAMA Wiscott-Aldrich inhibitor Haematological Acute Lung Autoimmune Severe Atopic COPD Syndrome HIV, HIV PrEP Malignancies Injury HCV Diseases Dermatitis
dolutegravir + GSK2998728† gepotidacin GSK3377794† # GSK2245035 GSK3228836† GSK2982772 rilpivirine TTR production Type 2 NY-ESO-1 TCR TLR7 agonist Antisense RIP1 kinase inhibitor Integrase inhibitor topoisomerase Sarcoma, Mult. oligonucleotide inhibitor † + NNRTI inhibitor Myel., Melanoma Psoriasis, RA, Subject to exercise of option HIV FAP Bacterial Inf. Ovarian, NSCLC Asthma HBV UC # Subject to collaborator agreement
Benlysta sirukumab GSK3359609 GSK3191812 belimumab + GSK3050002 ^ EU filing Subcutaneous IL-6 mAb ICOS agonist mAb TSLP dAb CD20 CCL20 mAb * USAN, INN approval pending BLyS mAb Solid tumours, BLyS+CD20 Giant Cell Haematological Sjogren’s Psoriatic SLE Arteritis Malignancies Asthma Syndrome Arthritis 136 Q&A