Gsk Plc · LSE:GSK
Gsk — Investor Day (July 2018)
48 slides from Gsk's investor day presentation, Jul 25, 2018
Slide 1: A new approach to R&D at GSK
A new approach to R&D at GSK Dr. Hal Barron 25 July 2018
Slide 2: Cautionary statement regarding forward-looking statements
Cautionary statement regarding forward-looking statements This presentation may contain 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 t
Slide 3: GSK has a strong presence and history of leadership in four major areas
Innovation GSK has a strong presence and history of leadership in four major areas Leadership in Respiratory Medicine Leadership in HIV/AIDS Leadership in Global Health Science Leadership in Vaccines and partnership 3
Slide 4: Driving our growth outlook beyond 2020
Innovation Driving our growth outlook beyond 2020 2021-2026 ‘091 (TLR4) – 44‘756 (CXCR2) 2018-2020 ‘165 (aGM-CSF) ’254 (HIV MI) ‘762 (BET inhibitor) ‘794 (NY ESO-1) Continuing ‘404/’836 (HBV) ‘847 (IL33R) ‘557 (PI3Kδ) ‘863 (HIF-PHI) growth drivers Shingrix Trelegy ‘595 (PRMT5 inhibitor) ‘944 (topois
Slide 5: High performing businesses reinvent themselves
Innovation High performing businesses reinvent themselves Source: “Reinvent your business before it’s too late”, Paul Nunes and Tim Breen, Harvard Business review, Jan-Feb 2011 The key is understanding what problem you are trying to solve, and what levers you have to engender the change 5
Slide 6: Science X Technology X Culture
Science X 3 Components to Technology our new R&D approach X Culture
Slide 7: Science X Technology X Culture
The industry needs more innovative medicines for patients with real unmet needs. Science Drugs that modulate the immune system X have had profound effects on patients with many different diseases. Technology Our scientific understanding of the role the X immune system plays in the development of hum
Slide 8: Drugs that modulate the immune system have had profound effects on patients
Innovation Drugs that modulate the immune system have had profound effects on patients with many different diseases Tomorrow Neurodegeneration Cardiovascular Metabolic Ophthalmology Hepatology Osteoarthritis ? Ageing 2011 Immuno-oncology onwards 1990 Autoimmune Diseases onwards rheumatology, lupus I
Slide 9: Scientific understanding of the role the immune system plays in disease is expanding
Innovation Scientific understanding of the role the immune system plays in disease is expanding Once virtually ignored, microglia, the resident immune cells of the CNS, have recently taken center stage in research for their roles in CNS health and disease. 9
Slide 10: Broad portfolio with strong focus in immunology
Innovation Broad portfolio with strong focus in immunology Phase 1 Phase 2 Pivotal/Registration Vaccines 2831781* (LAG3) ulcerative colitis 3196165* (GM-CSF inhibitor) RA Benlysta + Rituxan SLE** Rotavirus - Phase 3 3008348 (aVb6 integrin antagonist) IPF 3389404*/3228836* (HBV ASO) HBV cabotegravir*
Slide 11: GSK'165 (aGM-CSF): potential for a disease modifying effect in rheumatoid arthritis
GSK‘165 (aGM-CSF): potential for a disease modifying effect in Innovation rheumatoid arthritis (RA) with a unique impact on pain ̶ GM-CSF is a pro-inflammatory cytokine that induces ̶ Unmet need remains in RA despite differentiation and proliferation of granulocytes and macrophages development of ne
Slide 12: GSK'781: targeting the inflammatory cascade through depletion of LAG-3+ T cells
Innovation GSK‘781: targeting the inflammatory cascade through depletion of recently activated LAG-3+ T cells LAG-3 ̶ Lymphocyte Activation Gene-3 ̶ Marker of early T-cell activation The (predominantly expressed on newly target activated CD4+ & CD8+ T-cells) ̶ Negative regulator of T-cell response ̶
Slide 13: Experimental medicine studies support UC as lead indication
Innovation Experimental medicine studies support UC as lead indication Gut transcript levels correlate with LAG3+ cell numbers (IHC) reduce in responders endoscopic index of disease activity* but not non responders to established biologics * unpublished Slevin et al. P064, ECCO 2018 Dose dependent d
Slide 14: GSK's expertise in immunology will enable success in immuno-oncology
Innovation GSK’s expertise in immunology will enable success in immuno-oncology Monoclonal Antibodies Epigenetic Cellular Cell Therapy Therapies Modulators NY-ESO-1 PRMT1 Synthetic/small Molecules PRMT5 BET Immune-modulators BCMA ICOS TLR4 OX40 PI3kβ STING 14
Slide 15: GSK'916: First-in-class anti-BCMA ADC agent for treatment of multiple myeloma
Innovation GSK ‘916: First-in-class anti-BCMA ADC agent for treatment of multiple myeloma ̶ Multiple myeloma, also known as plasma cell ̶ BCMA plays a key role in plasma cell survival myeloma, The ̶ It is found on the surfaces of plasma cells and is is a cancer of plasma cells, a type of white blood
Slide 16: GSK'916 anti-BCMA ADC: robust single agent activity in heavily pre-treated patients
Innovation GSK’916 anti-BCMA ADC: robust single agent activity in heavily pre-treated/refractory patients Drug, Sponsor Line of therapy; Trial ORR mPFS mOS 1Kyprolis‡ (IV), monotherapy 3L+, Single arm, N=266 23.7% 3.7m 15.6m Amgen 2Darzalex‡ (IV), monotherapy 4L+, Single arm, N=106 29.2% 3.7m 17.5m
Slide 17: GSK'916: broad development plan initiated
Innovation GSK‘916: broad development plan initiated First launch in 4L in 2020; 2L launch planned for 2023 Study start Est launch Development strategy for use in: relapsed/ DREAMM-1 pilot ‘916 monotherapy, single arm, n=73 2014 --- refractory patients DREAMM-2 pivotal daratumumab failures ‘916 mono
Slide 18: Early stage oncology portfolio with near term data read outs
Innovation Early stage oncology portfolio with near term data read outs GSK’609 ICOS agonist GSK’595 PRMT5 inhibitor – humanised IgG4 anti-ICOS agonist – First-in-class agent with potential monoclonal antibody, engineered to broad activity across multiple provide non-depleting ‘best in class’ haemat
Slide 19: Science X Technology X Culture
Science Drug discovery and development is very risky X with <10% of drugs that undergo clinical testing ultimately becoming medicines1. Technology Medicines with genetic validation succeed X nearly 2x more often than those without2. Culture 1. Parsing clinical success rates. Asher Mullard. Nature Re
Slide 20: Genetically validated targets have a higher probability of success
Innovation “Genetically validated” targets have a higher probability of success1 Drugs with human genetic evidence nearly 2x more likely to be successful1 GWAS focuses on diseases of interest and looks for genetic associations SNP3 Target-indication pairs SNP2 SNP4 Preclinical Phase I Phase II SNP1
Slide 21: PCSK9: the power of genetically validated targets
Innovation PCSK9: the power of genetically validated targets Heterozygous carriers of PCSK9 loss-of-function Evolocumab and clinical outcomes in patients alleles have lower LDL and fewer CV events with cardiovascular disease 9.7% Cumulative incidence (%) 1.2% 11 years for validation of genetics to b
Slide 22: PheWAS can enable discovery of novel genetic associations
Innovation PheWAS can enable discovery of novel genetic associations PheWAS focuses on SNP/gene of interest and looks for phenotype associations T allele of RS11591147 high BP diabetes high TG obesity low LDL SNP2 22 PheWAS: phenome-wide association study BP: blood pressure; TG: trigylcerides; LDL:
Slide 23: A new approach to drug discovery is needed to make this a reality
Innovation A new approach to drug discovery is needed to make this a reality ? 2018 2017 2015 23
Slide 24: A new approach to drug discovery is needed to make this a reality
Innovation A new approach to drug discovery is needed to make this a reality 2018 2017 2015 24
Slide 25: A new approach to drug discovery is needed to make this a reality
Innovation A new approach to drug discovery is needed to make this a reality The picture can't be displayed. 25
Slide 26: 23andMe database metrics: massive engaged database
Innovation 23andMe database metrics: massive engaged database 5m+ >80% 1.5b+ customers consent to survey research and questions recontact answered Genotype data Phenotype data Biobanked samples Longitudinal data Ability to re-contact No individual will be identifiable to GSK. Continued protection of
Slide 27: LRRK2: a genetically validated target for Parkinson's Disease
Innovation Leucine rich-repeat kinase 2 (LRRK2): a genetically validated target for Parkinson’s Disease ̶ 2nd most prevalent neurodegenerative disease ̶ Genetically validated targets provide an opportunity to The ̶ Leucine rich-repeat kinase 2 (LRRK2) treat earlier in the disease target is a genetic
Slide 28: LRRK2 inhibitor programme: 23andMe's advantage to expedite clinical trial recruitment
Innovation LRRK2 inhibitor programme: 23andMe’s advantage to expedite clinical trial recruitment Identifying eligible participants is a time intensive 23andMe database currently includes: and costly process – >10,000 re-contactable individuals with Parkinson’s Disease In the US: – >3,000 re-contacta
Slide 29: 23andMe and GSK exclusive collaboration
Innovation 23andMe and GSK exclusive collaboration Collaboration offers scale, Improved target selection diversity, sustainability for advancing therapeutic programs (higher PoS, and safer, more effective medicines) Questionnaire yields unique phenotype information vs other biobanks Allows more effi
Slide 30: Science X Technology X Culture
Science Technology has been X a driver of innovation Technology in many industries, especially science X and medicine. Culture
Slide 31: Functional genomics: the power of gene editing to unravel biology at scale
Functional genomics: the power of gene editing to Innovation unravel biology at scale Reverse genetics (think PheWAS) is the process of going from genotype to phenotype All experiments Genetic interactions reveal functional relationships nature could do Genetic interaction maps systematically measur
Slide 32: Functional genomics combined with machine learning will be very powerful
Innovation Functional genomics (the power of gene editing) combined with machine learning will be very powerful Gene x Gene Functional Acceleration of annotation of the drug discovery human genome ~200 million combinations Prediction of X Deep learning disease-associated mutations Disease diagnosis
Slide 33: Human genetics and functional genomics
Innovation Human genetics and functional genomics Science and technology together to drive better R&D success “Artificial Intelligence is the new electricity and is changing industry after industry.” Human genetics Stanford School of Business lecture by Andrew Ng More high quality targets Machine le
Slide 34: Cell and Gene Therapy is a potentially disruptive technology
Innovation Cell and Gene Therapy is a potentially disruptive technology that has the potential to transform medicine GSK is positioned to lead the field through: Pioneer in autologous cell therapy Patented enabling technology Strong pipeline of candidate ̶ Early clinical and manufacturing ̶ Autologo
Slide 35: GSK'794: NY-ESO-1 – a potential first to market TCR-T cell therapy
Innovation GSK‘794: NY-ESO-1 – a potential first to market TCR-T autologous cell therapy for solid tumours NY-ESO-1c259 TCR-T: The ̶ NY-ESO-1 has significant expression in several tumour affinity-enhanced TCR enabling identification target types, including NSCLC, sarcoma and myeloma and killing of t
Slide 36: GSK'794 NY-ESO-1c259 TCR-T in synovial sarcoma
Innovation GSK’794 NY-ESO-1c259 TCR-T is transformational in improving ORR and mOS in synovial sarcoma ̶ Confirmed antitumour activity in 10/12 subjects treated Metastatic synovial sarcoma is incurable with standard therapy ̶ Tumour shrinkage over several months. 1.00 - ̶ Circulating NY-ESO-1c259T c
Slide 37: Expanding the power of our strategy through Business Development
Innovation Expanding the power of our strategy through Business Development ̶ Targets aimed at modulating the immune system Therapeutic New programs that ̶ Genetically validated targets opportunities ̶ Targets that complement our enhance our strategy current pipeline ̶ Human Genetics & Functional Ge
Slide 38: Science X Technology X Culture
Science X Culture matters. Technology A lot! X Culture
Slide 39: Culture change will drive solutions to problems that need to be fixed
Innovation Culture change will drive solutions to problems that need to be fixed Following Smart Single Focus Outstanding the science risk-taking accountable people decision making Therapeutic area and Incentivise people to Consensus can kill Aggressively resource Demand, develop and modality agnost
Slide 40: Smart risk-taking
Innovation Smart risk-taking Good outcome Bad outcome Success Smart risk-taking Good decision Celebrate the good decision and Needs to be celebrated to successful outcome foster innovation Lucky! A learning opportunity Bad decision Do not celebrate - luck is not a strategy 40
Slide 41: Focus: prioritisation is critical
Innovation Focus: prioritisation is critical “More organizations die of indigestion than starvation.” David Packard “I’m as proud of many of the things we haven’t done as the things we have done. Innovation is saying no to a thousand things.” Simplify. Simplify. Simplify. Steve Jobs 41
Slide 42: Refocusing to reinvest
Innovation Refocusing to reinvest 65 Decisions made to terminate, partner or divest 42 programmes were in clinical phase, and the >400 FTEs re-allocated to priority programmes programmessince April 2017* remainder were preclinical 42 *Includes transfer of Rare Disease assets to Orchard Therapeutics
Slide 43: Upcoming milestones that will inform our progress
Innovation Upcoming milestones that will inform our progress 2H 2018 1H 2019 2H 2019 1H 2020 2H 2020 Submission dolutegravir+lamivudine (D3) HIV fostemsavir (attachment inhibitor) HIV Trelegy asthma mepolizumab HES cabotegravir+rilpivirine HIV treatment GSK’916 (BCMA) 4L MM monotherapy mepolizumab N
Slide 44: New R&D approach will support the development of current clinical portfolio
Innovation New R&D approach will support the development of current clinical portfolio From To Science Backing the best assets, Spend spread thinly across and removing those that don’t look too many programmes promising (“shots on goal” strategy) Consensus-driven x Culture of accountability where sm
Slide 45: Science X Technology X Culture
Science We will seek to understand how the immune system causes disease in a therapeutic area agnostic manner and use human genetics to generate new targets and direct our focus X We will invest in advanced technologies (such as functional Technology genomics, machine learning and cell therapy) to l
Slide 46: Science X Technology X Culture = Next generation of medicines
Science X Technology X Culture = Next generation of medicines for patients
Slide 47: Thank you
Thank you
Slide 48: Q&A panel
Q&A panel Axel Hoos Kim Smith Gijs van den Brink Emmanuel Hanon Oncology Therapy Global Research and Immunoinflammation R&D Vaccines Area Medical Strategy, ViiV R&D Kevin Sin John Lepore R&D Pharmaceuticals Kate Knobil Patrick VallanceR&D Pipeline Business Development Chief Medical Officer President