Gsk Plc · LSE:GSK
Gsk — Technical Presentation (October 2018)
25 slides from Gsk's technical presentation, Oct 23, 2018
Slide 1: GSK'165: anti-GM-CSF antibody
GSK’165: anti-GM-CSF antibody A novel mechanism with potentially differentiated impact on pain in the treatment of Rheumatoid Arthritis 23 October 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: Agenda
Agenda GSK‘165: anti-GM-CSF antibody Dr Hal Barron Chief Scientific Officer and President R&D Results of BAROQUE Phase 2 study Dr Roy Fleischmann Clinical Professor of Medicine at the University of Texas Southwestern Medical Center Presentation Q&A RA market and commercial opportunity 20-25 mins 20-
Slide 4: Rheumatoid Arthritis (RA): a chronic and debilitating inflammatory disease
Rheumatoid Arthritis (RA): a chronic and debilitating inflammatory disease Disease background • RA is an autoimmune disease which causes inflammation in the joints and results in pain, swelling and stiffness • Estimated prevalence1,2: • Global: 24.5 million (~1% of 18+ world population) • US: 2.7 mi
Slide 5: Recent progress with new treatment options, but unmet need remains
Recent progress with new treatment options, but unmet need remains Substantial unmet need remains 2000+ 2005+ 2015+ aTNFs - Most effective current therapies only achieve CTLA 4 ~50% disease improvement in <50% of patients IL-6 JAKs - Even with multiple targeted therapies only 30% of patients achieve
Slide 6: GSK'165 (aGM-CSF): potential for a disease modifying effect in RA with a unique impact on pain
GSK‘165 (aGM-CSF): potential for a disease modifying effect in rheumatoid arthritis (RA) with a unique impact on pain ̶ GM-CSF is a pro-inflammatory cytokine that induces differentiation and proliferation of granulocytes and macrophages The ̶ One of the first cytokines detected in human synovial flu
Slide 7: Strong rationale for moving forward
Strong rationale for moving forward ̶ Wealth of preclinical data in multiple animal models, Strong preclinical including evidence specific to pain1 data Interesting ̶ GM-CSF upregulates CCL17 production in human monocytes and macrophages biology AND is required for GM-CSF dependent arthritic pain an
Slide 8: Key data demonstrating efficacy of GSK'165 aGM-CSF from the BAROQUE Phase 2 study
Key data demonstrating efficacy of GSK’165 aGM-CSF from the BAROQUE Phase 2 study Presented at ACR 22 October 2018
Slide 9: Phase 2 study design
Phase 2 study design A randomised, multicentre, double-blind, parallel group, placebo controlled study with novel features to support a 52 week study GSK3196165 or placebo administered as 5 weekly SC injections, followed by every other week injections GSK3196165 180mg + MTX (n=37) N=222 Adult patien
Slide 10: Baseline patient demographic characteristics
Baseline patient demographic characteristics Typical, established RA MTX-IR population; well balanced across treatment groups GSK3196165 + MTX Placebo + MTX 22.5mg 45mg 90mg 135mg 180mg (n=37) (n=37) (n=37) (n=37) (n=37) (n=37) Age (y), mean (SD) 50.0 (11.33) 48.4 (11.31) 52.8 (12.22) 52.7 (11.28) 4
Slide 11: Baseline RA disease characteristics
Baseline RA disease characteristics Well balanced but with high DAS28(CRP) and HAQ-DI GSK3196165 + MTX Placebo + MTX 22.5mg 45mg 90mg 135mg 180mg (n=37) (n=37) (n=37) (n=37) (n=37) (n=37) DAS28(CRP), mean (SD) 6.2 (0.82) 6.4 (0.82) 6.1 (0.74) 6.2 (0.84) 6.3 (0.92) 6.0 (0.88) SDAI (0–86), mean (SD) 4
Slide 12: Rationale for weekly dosing going forward
Rationale for weekly dosing going forward GSK3196165 22.5mg GSK3196165 45mg GSK3196165 90mg GSK3196165 135mg GSK3196165 180mg Series6 7000 Mean (SD) serum concentration (ng/mL) 6000 6000 Mean (SD) serum concentration 5000 5000 4000 4000 (ng/mL) 3000 3000 2000 2000 2000 1000 1000 0 0 -1000 Axis Title
Slide 13: Patient disposition on randomised treatment
Patient disposition on randomised treatment 70% of placebo patients switched to GSK’165 180mg dose at Wk12 early escape point Screened Excluded (n=304) N=526 SF Rate= 58% Randomized N=222 Placebo GSK3196165 GSK3196165 GSK3196165 GSK3196165 GSK3196165 n=37 22.5mg n=37 45mg n=37 90mg n=37 135mg n=37 1
Slide 14: Significantly higher ACR 20 response rates at Week 12 with GSK'165 versus placebo
Significantly higher response rates at Week 12 with GSK’165 versus placebo ACR 20 at Week 12 60 Δ (95% CI): 40.5% (21.6, 59.5) 50 achieving ACR 20 40 Patients, % 30 20 10 * ** *** ** *** 11 35 41 51 41 51 0 Placebo GSK3196165 GSK3196165 GSK3196165 GSK3196165 GSK3196165 22.5mg 45mg 90mg 135mg 180mg *
Slide 15: Rapid onset of action during weekly dosing phase
Rapid onset of action during weekly dosing phase Clinical Response: DAS28(CRP) and DAS28(CRP) <2.6 DAS28(CRP) <2.6 (W24; primary endpoint) N (%) OR (95% CI); p-value Placebo 1 (3) 0.5 Placebo LS mean (SE) change from GSK3196165 180mg 5 (14) 5.40 (0.60, 48.83); p=0.134 baseline in DAS28(CRP) GSK31961
Slide 16: Rapid and substantial improvement in joint counts
Rapid and substantial improvement in joint counts Swollen Joint Count (SJC) 66 & Tender Joint Count (TJC) 68 Placebo GSK3196165 22.5mg GSK3196165 45mg GSK3196165 90mg GSK3196165 135mg GSK3196165 180mg 2 2 Tender Joint Count (TJC) 68 Swollen Joint Count (SJC) 66 LS mean (SE) change from baseline in L
Slide 17: Rapid and substantial improvement in pain, CRP reduced but not suppressed
Rapid and substantial improvement in pain, CRP reduced but not suppressed Placebo GSK3196165 22.5mg GSK3196165 45mg GSK3196165 90mg GSK3196165 135mg GSK3196165 180mg 5 Pain 1.2 CRP LS geometric mean (95% CI) ratio to LS mean (SE) change from baseline in pain 0 1.0 baseline in CRP -5 -5.44 -7.07 0.72
Slide 18: Marked clinical response on Clinical Disease Activity Index (CDAI)
Marked clinical response on Clinical Disease Activity Index (CDAI) LS mean (SE) change from baseline in 5 CDAI 0 -6.59 -4.95 -5 Placebo GSK3196165 22.5mg -10 CDAI GSK3196165 45mg -15 GSK3196165 90mg -20 -17.14*** GSK3196165 135mg -25 GSK3196165 180mg -23.23*** -30 Repeated measures analysis adjusted
Slide 19: Totality of data supports further studies
Totality of data supports further studies Benefits across multiple endpoints, notably in pain and swollen and tender joint counts Placebo + MTX GSK3196165 180 mg + MTX (n=37) (n=37) Difference from placebo Clinical endpoint at Week 12 LS mean change from baseline (SE) (95% CI); p-value DAS 28(CRP) -
Slide 20: Overall AE profile unremarkable: majority were of mild or moderate intensity
Overall AE profile unremarkable: majority were of mild or moderate intensity Pre-rescue Post-rescue GSK3196165 + MTX GSK3196165 + MTX Placebo Placebo 22.5mg 45mg 90mg 135mg 180mg 22.5mg 45mg 90mg 135mg + MTX + MTX Pre-rescue, n (%) (n=37) (n=37) (n=37) (n=37) (n=37) Post rescue, n (%) (n=30) (n=27)
Slide 21: RA market and commercial opportunity
RA market and commercial opportunity Luke Miels, President, Global Pharmaceuticals
Slide 22: Evolving treatment paradigm provides opportunity for new mechanisms of action
Evolving treatment paradigm provides opportunity for new mechanisms of action Conventional First line targeted Second+ line DMARDs targeted aTNFs Total TNFs 82% CD-20 (Humira, Enbrel, Cimzia (rituximab) Remicade, Simponi) CTLA4 (abatacept) Diagnosis MTX IL-6 18% (tocilizumab, Total Alternate sarilum
Slide 23: RA market growth to be driven by new mechanisms
RA market growth to be driven by new mechanisms RA market decline due to biosimilars; value opportunity for new MOA’s Annual WW RA sales, £m1 14,000 Opportunity for alternative 12,000 mechanisms of action 10,000 Sales, £m 8,000 6,000 Importance of demonstrating 4,000 differentiated efficacy 2,000 -
Slide 24: Strong rationale for moving forward
Strong rationale for moving forward Data supports ̶ Exciting asset with a novel mechanism of action which has shown compelling data across traditional endpoints for RA further supporting further and accelerated clinical development development Next ̶ Plans for discussions with regulators with a view
Slide 25: do more feel better live longer
do more feel better live longer &A