Gsk Plc · LSE:GSK
Gsk — ESMO Investor call 2019
53 slides from Gsk's conference presentation, Sep 30, 2019
Slide 1: ESMO Investor call: accelerating our oncology pipeline
ESMO Investor call: accelerating our oncology pipeline 30 September 2019
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: Agenda
Agenda Accelerating our oncology Dr Hal Barron pipeline Chief Scientific Officer, President R&D Dr Antonio González-Martín Results of PRIMA Head of Medical Oncology, Clinica Universidad de Navarra Putting PRIMA in context Dr Hal Barron Chief Scientific Officer, President R&D Oncology strategy & data
Slide 4: Science x Technology
Strengthening our R&D Science pipeline through a focus on x science related to the immune Technology system, the use of human x genetics, and advanced Culture technologies
Slide 5: GSK Oncology: building on a strong foundation and investing for future performance
GSK Oncology: building on a strong foundation and investing for future performance Smart business Strong internal R&D Strengthening in development capabilities market operations 17 assets in oncology - Tesaro acquisition - High calibre scientists - Tesaro accelerated pipeline within clinical teams b
Slide 6: GSK Oncology: building on a strong foundation and investing for future performance
GSK Oncology: building on a strong foundation and investing for future performance Smart business Strong internal R&D Strengthening in development capabilities market operations 17 assets in oncology - Tesaro acquisition - High calibre scientists - Tesaro accelerated pipeline within clinical teams b
Slide 7: Results of PRIMA
Results of PRIMA Dr Antonio González Martín, Head of Medical Oncology, Clinica Universidad de Navarra
Slide 8: Niraparib is effective in recurrent ovarian cancer (BRCAmut and BRCAwt)
Niraparib is effective in recurrent ovarian cancer (BRCAmut and BRCAwt) • Advanced ovarian cancer is a leading cause of cancer deaths in women with up to 85% recurrence after completion of standard first-line platinum-based chemotherapy1 • Despite current options for maintenance treatment, there is
Slide 9: PRIMA was designed to address the unmet need in 1L advanced ovarian cancer
PRIMA was designed to address the unmet need in 1L advanced ovarian cancer Hypothesis: PRIMA/ENGOT-OV26/GOG-3012 was designed to test the efficacy and safety of niraparib therapy after response to platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancer, including those a
Slide 10: PRIMA trial design
PRIMA trial design Stratification Factors Patients with newly-diagnosed OC at high risk for recurrence after response to 1L platinum- • Neoadjuvant chemotherapy administered: Yes or no based chemotherapy • Best response to first platinum therapy: CR or PR • Tissue homologous recombination test statu
Slide 11: PRIMA tissue test for homologous recombination
PRIMA tissue test for homologous recombination Testing for Homologous Recombination Deficiency (HRd) and Proficiency (HRp) Next generation sequencing of DNA from tumor tissue (Myriad Genetics myChoice® Test) Provides a score based on algorithmic measurement of 3 tumor factors: • Loss of heterozygosi
Slide 12: PRIMA enrollment and outcomes
PRIMA enrollment and outcomes 733 randomized 5 did not receive intervention 3 HRd 728 received intervention 370 HRd 484 received niraparib 244 received placebo 307 discontinued* 175 discontinued* ▪ 58 due to AE 245 HRd 125 HRd ▪ 5 due to AE ▪ 218 due to PD (45%) ▪ 162 due to PD (66%) ▪ 12 patient re
Slide 13: PRIMA patient characteristics and baseline demographics
PRIMA patient characteristics and baseline demographics Niraparib Placebo Overall Characteristic (n=487) (n=246) (N=733) – 35% of patients were Stage IV Age, median (range), years 62 (32, 85) 62 (33,88) 62 (32, 88) Weight, median, kg 66 66 66 – 99.6% with Stage III had residual Stage at initial diag
Slide 14: PRIMA primary endpoint, PFS benefit in the HR-deficient population
PRIMA primary endpoint, PFS benefit in the HR-deficient population 100 Hazard ratio: 0.43 (95% CI, 0.31–0.59) 57% reduction in risk of relapse or death 90 p<0.001 with niraparib Progression-free Survival (%) 80 Niraparib Placebo 70 (n=247) (n=126) 60 Median PFS Niraparib 50 months 21.9 10.4 40 (95%
Slide 15: PRIMA primary endpoint, PFS benefit in the overall population
PRIMA primary endpoint, PFS benefit in the overall population 100 Hazard ratio: 0.62 (95% CI, 0.50–0.76) 38% reduction in risk of relapse or death 90 p<0.001 with niraparib Progression-free Survival (%) 80 Niraparib Placebo 70 (n=487) (n=246) 60 Median PFS 50 months 13.8 8.2 40 (95% CI) (11.5–14.9)
Slide 16: PRIMA exploratory analysis, PFS benefit in pre-specified groups
PRIMA exploratory analysis, PFS benefit in pre-specified groups HR for PFS (95% CI) Overall 0.62 (0.50–0.76) Age group <65 years 0.61 (0.47–0.81) ≥65 years 0.53 (0.38–0.74) Stage of disease at initial diagnosis III 0.54 (0.42–0.70) IV 0.79 (0.55–1.12) Neoadjuvant chemotherapy Yes 0.59 (0.46–0.76) No
Slide 17: PRIMA PFS benefit in biomarker subgroups
PRIMA PFS benefit in biomarker subgroups Homologous Recombination Deficient (HRd) HRd/BRCAmut HRd/BRCAwt HR-proficient 100 100 100 Hazard ratio: 0.40 (95% CI, 0.27–0.62) Hazard ratio: 0.50 (95% CI, 0.31–0.83) Hazard ratio: 0.68 (95% CI, 0.49–0.94) 90 p<0.001 90 p=0.006 90 p=0.020 Progression-free Su
Slide 18: PRIMA key secondary endpoint, overall survival
PRIMA key secondary endpoint, overall survival (11% data maturity) Overall Population HR-deficient HR-proficient 100 100 100 Niraparib 90 Niraparib 90 90 Niraparib 80 80 Placebo 80 Placebo Overall Survival (% ) 70 70 70 60 60 60 Placebo 50 50 50 Hazard ratio: 0.70 (95% CI, 0.44–1.11) Hazard ratio: 0
Slide 19: PRIMA safety overview
PRIMA safety overview Niraparib Placebo Adverse Event, no. (%) (n=484) (n=244) Any TEAE 478 (98.8) 224 (91.8) Grade ≥3 341 (70.5) 46 (18.9) Led to treatment discontinuation 58 (12.0) 6 (2.5) Led to dose reduction 343 (70.9) 20 (8.2) Led to dose interruption 385 (79.5) 44 (18.0) TEAEs leading to deat
Slide 20: PRIMA Conclusions
PRIMA Conclusions – Available therapies and active surveillance do not address the high unmet need for many patients with newly diagnosed advanced ovarian cancer after platinum-based chemotherapy – Niraparib therapy in patients with advanced ovarian cancer provided a clinically significantly improve
Slide 21: Putting PRIMA in context
Putting PRIMA in context Dr Hal Barron, Chief Scientific Officer and President R&D
Slide 22: Why was Tesaro a smart risk?
Why was Tesaro a smart risk? The questions: The hypotheses: Conclusions: 1: Does Zejula offer a benefit to PARP inhibitors have efficacy women with ovarian cancer with an beyond gBRCA patients and HR deficiency (ie HRD positive) in benefit patients with other forms PRIMA met the primary the first li
Slide 23: Caution needs to be taken when making cross trial comparisons
Caution needs to be taken when making cross trial comparisons, especially when patient populations vary Hazard ratio better shows biological impact than mPFS PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 114
Slide 24: Comparing PARPi and bevacizumab in 1L ovarian cancer
Comparing PARPi and bevacizumab in 1L ovarian cancer PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 1140 1873 1528 Overall population 0.62 0.59 0.68 0.73 0.87 HR deficient BRCAmut 0.40 0.30 0.31 0.44 ND (~20%
Slide 25: Comparing PARPi and bevacizumab in 1L ovarian cancer
Comparing PARPi and bevacizumab in 1L ovarian cancer First conclusion PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 1140 1873 1528 Overall 0.62 0.59 0.68 0.73 0.87 population HR deficient BRCAmut 0.40 0.30 0
Slide 26: Comparing PARPi and bevacizumab in 1L ovarian cancer
Comparing PARPi and bevacizumab in 1L ovarian cancer Second conclusion PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 1140 1873 1528 Overall 0.62 0.59 0.68 0.73 0.87 population HR deficient BRCAmut 0.40 0.30
Slide 27: Comparing PARPi and bevacizumab in 1L ovarian cancer
Comparing PARPi and bevacizumab in 1L ovarian cancer Third conclusion PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 1140 1873 1528 Overall 0.62 0.59 0.68 0.73 0.87 population HR deficient BRCAmut 0.40 0.30 0
Slide 28: Comparing PARPi and bevacizumab in 1L ovarian cancer
Comparing PARPi and bevacizumab in 1L ovarian cancer PRIMA1 SOLO-12 PAOLA-13 VELIA4 GOG-2185 ICON76 niraparib olaparib bevacizumab veliparib bevacizumab bevacizumab +/- olaparib N 733 391 806 1140 1873 1528 Overall 0.62 0.59 0.68 0.73 0.87 population HR deficient BRCAmut 0.40 0.30 0.31 0.44 ND (~20%
Slide 29: Could Zejula's unique PK profile explain the benefit in HRD- patients?
Could Zejula’s unique PK profile explain the benefit in HRD- patients? At steady state, the concentration of niraparib is higher in the tumour than the plasma BRCAwt ovarian cancer model* “Our results show that at steady state, tumor exposure to niraparib is 3.3 times greater than plasma exposure in
Slide 30: Clinical confirmation of higher exposure to niraparib in tumour versus plasma
Clinical confirmation of higher exposure to niraparib in tumour versus plasma in patients with breast cancer Results provide the first data of the intra-tumour concentration of niraparib in the clinical setting Concentration of niraparib was ~36-fold greater in tumour tissue than in plasma Confirms
Slide 31: GSK Oncology: data at ESMO ICOS: results from INDUCE-1
GSK Oncology: data at ESMO ICOS: results from INDUCE-1 Axel Hoos, SVP Oncology R&D
Slide 32: GSK Oncology: building on a strong foundation and investing for future performance
GSK Oncology: building on a strong foundation and investing for future performance Smart business Strong internal R&D Strengthening in development capabilities market operations 17 assets in oncology - Tesaro acquisition - High calibre scientists - Tesaro accelerated pipeline within clinical teams b
Slide 33: Oncology R&D: strategy and scientific focus
Oncology R&D: strategy and scientific focus Maximise patient survival through transformational medicines Immuno- Cancer Oncology Synthetic Experimental Oncology Epigenetics Cell Therapy Lethality Medicine Clinical Optimise use of Advance IO Establish Establish biomarker strategy PARP inhibitors to n
Slide 34: Data at ESMO: oncology clinical pipeline
Data at ESMO: oncology clinical pipeline Representing 8 clinical programs across four focus areas Phase 1 Mechanism Phase 1 expansion Phase 3 (FTIH) (pivotal) / Phase 2 PARP inhibitor (Zejula, niraparib)* First line maintenance ovarian, other solid tumors under investigation Anti-BCMA ADC (belantama
Slide 35: GSK'609 ICOS receptor agonist
GSK’609 ICOS receptor agonist Differentiated MOA with encouraging clinical data at ESMO 2019 • ICOS, a member of the CD28 family of co-stimulatory receptors, has a pivotal role in the proliferation, differentiation, survival, and function of T cells T-cell priming/ Local antigen Memory • Highly upre
Slide 36: ICOS: checkpoint modulation beyond PD-1
ICOS: checkpoint modulation beyond PD-1 Association with successful IO mechanisms of action increases clinical PoS CTLA-4 and PD-1 Kinetics of Clinical Activity Agonist receptor families Melanoma and Head & Neck Cancer ORR DOR OS @ 2y B7 - CD28 Ipilimumab 11% >2y 22% (CTLA-4) (same as Melanoma 2L CT
Slide 37: GSK'609: first time monotherapy activity seen with an ICOS agonist
GSK’609: first time monotherapy activity has been seen with an ICOS agonist in multiple tumour types Change from baseline in tumour Best tumour response HNSCC measurement by dose level (irRECIST) 270 75 120 Maximum percent change Percentage change from baseline in sum of from baseline (%) 90 lesion
Slide 38: GSK'609: early data point to ORR of 24% in combination with pembrolizumab
GSK’609: early data point to ORR of 24% in combination with pembrolizumab with durable responses Change from baseline in tumour Best tumour response measurement by dose level (irRECIST) from baseline in sum of lesion 50 Maximum percent change 170 Percentage change from baseline (%) irPD 110 ††† diam
Slide 39: GSK'609: responses not correlated to PD-L1 expression
GSK’609: responses not correlated to PD-L1 expression suggesting ICOS agonist activity irRecist confirmed response versus CPS score 90 80 70 PD-L1 CPS 60 50 denotes CPS <1 was imputed to 0.5 to 40 enable graphing; area between the dashed lines indicates 1 ≤ CPS <20; the 30 median is indicated by a b
Slide 40: GSK'609: safety and tolerability consistent with results previously reported
GSK’609: safety and tolerability consistent with results previously reported Monotherapy cohorts Combination cohort (Part 1A and 1B, N=22) (Part 2A and 2B, N=58) Asthenia Diarrhoea Fatigue Diarrhoea Fatigue Dysphagia Hypothyroidism Asthenia Nausea Rash 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Slide 41: GSK'609: progressing to advanced trials and novel combinations
GSK’609: progressing to advanced trials and novel combinations Study start Read-out Solid INDUCE-1 POC Relapsed/refractory selected solid Open label dose escalation and expansion study of GSK’609 monotherapy and combination with 2016 NA tumours tumours pembrolizumab n= >500 Open label dose escalatio
Slide 42: Building our oncology commercial capabilities
Building our oncology commercial capabilities Luke Miels, President Global Pharmaceuticals
Slide 43: GSK Oncology: building on a strong foundation and investing for future performance
GSK Oncology: building on a strong foundation and investing for future performance Smart business Strong internal R&D Strengthening in development capabilities market operations 17 assets in oncology - Tesaro acquisition - High calibre scientists - Tesaro accelerated pipeline within clinical teams b
Slide 44: Building our oncology commercial capability
Building our oncology commercial capability Improved engagement with HCPs 3 potential oncology launches in 2020 Updated HCP engagement policies to improve how we Zejula 1L maintenance therapy (PRIMA) presented at help prescribers understand new data and clinical ESMO 2019 experience with our innovat
Slide 45: Expect increase in use of PARPs following ESMO data
Expect increase in use of PARPs following ESMO data with 1L monotherapy taking leading share PARPs underutilised in 1L Avastin combination Zejula uniquely positioned and 2L ovarian cancer presents challenges with PRIMA data Utilisation % of eligible maintenance patients (US) • Combination of PARP +
Slide 46: Q&A
do more feel better live longer Q&A
Slide 47: Dr Hal Barron
Dr Hal Barron Hal joined GSK as Chief Scientific Officer and President, R&D on 1 January 2018. He is a member of the Board and the Corporate Executive Team. His previous role was President, R&D at Calico (California Life Company). Prior to this, Hal was Executive Vice President, Head of Global Produ
Slide 48: Dr Antonio González-Martín
Dr Antonio González-Martín Dr González-Martín graduated in medicine at University of Navarra in Pamplona, and subsequently trained in medical oncology at University Hospital Ramón y Cajal in Madrid from 1994 to 1997. During part of 1997 he attended as an observer to The Mount Sinai School of Medicin
Slide 49: Dr Axel Hoos
Dr Axel Hoos Axel is SVP, R&D Governance Chair, and Therapeutic Area (TA) Head for Oncology at GSK, responsible for discovery and development in Oncology. As R&D governance chair he oversees technical and funding review committees. Axel also serves as Chairman of the Board of Trustees of the Sabin V
Slide 50: Luke Miels
Luke Miels Luke joined GSK as President, Global Pharmaceuticals in September 2017. He is a member of the Corporate Executive Team. At GSK, he is responsible for commercialising a portfolio of medicines and vaccines with annual sales of more than £20 billion and operations in over 100 markets. His pr
Slide 51: Christine Roth
Christine Roth Christine re-joined GSK as SVP, Global Oncology Therapy Area Head in December 2017, reporting to Luke Miels. As the global commercial lead for oncology, Christine is a member of the Pharmaceutical Leadership Team, Forecast Review Committee, Research Investment Board, Development Revie
Slide 52: Jenn Christensen
Jenn Christensen Jennifer completed her masters degree in Organic Chemistry from Brandeis University, Massachusetts. She has worked at a number of biotech companies including Tesaro, Xanthus/ Antisoma and Datide Research Laboratories. Jennifer joined Tesaro in 2011 to initially lead the Varubi progr
Slide 53: Dr Marc Ballas
Dr Marc Ballas Marc S Ballas, MD, MPH is an Albert Einstein School of Medicine trained physician who completed his medical oncology/hematology at NIH and practiced as Assistant Professor at NYU Langone School of Medicine before joining the pharmaceutical industry. Early on, he has been involved in t