Gsk Plc · LSE:GSK
Gsk — Technical Presentation (2010)
18 slides from Gsk's technical presentation, 2010
Slide 1: GSK Vaccines: Building a Therapeutic Portfolio
GSK VACCINES: BUILDING A THERAPEUTIC PORTFOLIO Vincent Brichard, MD Vice President & Head of Immunotherapeutics, GSK Biologicals
Slide 2: Immunotherapy in action
Immunotherapy in action Cytolytic T Lymphocyte (CTL) Killed (“lysed”) Tumour cell tumour cell ± 20 min (in vitro) 2
Slide 3: Antigen-Specific Cancer Immunotherapeutics (ASCI): MAGE-A3
Antigen-Specific Cancer Immunotherapeutics (ASCI): MAGE-A3 • Genuine target: identified via screening with anti-tumour killer T-cells • Genuinely tumour-specific: not expressed in normal cells • Easy to detect in patients (RT-PCR on tumour tissue) • Present in major tumour types • Lung 35-50% • Blad
Slide 4: Lung cancer and melanoma: need for improved therapies
Lung cancer and melanoma: need for improved therapies Lung cancer: leading cause of cancer death • More than 1.3 million new cases a year worldwide • NSCLC ≈ 85% of lung cancer • More than 1.1 million deaths a year worldwide • Expected 5-year survival of only 15% • Current treatments: surgery, chemo
Slide 5: MAGE-A3 clinical development programme
MAGE-A3 clinical development programme Stage IV melanoma Proof of Activity PoC in NSCLC MAGRIT Study 300 μg Dble-blind, placebo selected Double-blind, placebo-controlled Phase II study N=2270 n=182 MAGE-A3 + AS02B MAGE-A3 + AS15 + AS15 selected Randomized, open n=75 New Adjuvant System MAGE-A3 + AS0
Slide 6: MAGE-A3 proof of concept: NSCLC phase II data
MAGE-A3 proof of concept: NSCLC phase II data NSCLC Double blind, DFS and Survival Adjuvant setting – stage IB-II placebo controlled phase II 180 patients randomized After surgery – no chemo 2:1 MAGE-A3/AS02B:placebo Interim end 2005 1 MAGE-A3 Placebo 0.9 Disease Free Interval Distribution 0.8 0.7 0
Slide 7: MAGE-A3 proof of concept: melanoma phase II data
MAGE-A3 proof of concept: melanoma phase II data Melanoma Tumour response / Surv. Metastatic setting – stage III-IVa Randomized phase II 68 patients randomized 1:1 MAGE-A3 AS02B vs AS15 Progressive Results 2006-2009 100 Median survival (95%CI): AS15 AS15 : 31.1 months AS02B 90 AS02B : 19.9 months 80
Slide 8: Genetic signature predictive of clinical response
Genetic signature predictive of clinical response Affymetrix platform : HG-U133.Plus 2.0 gene chips covering 47,000 transcripts Clinical benefit Progressive disease (Responders) (Non-Responders) 8
Slide 9: Predictive signature: benefit in melanoma
Predictive signature: benefit in melanoma Gene signature positive % patients AS15 GS+ AS15 : HR: 0.268 (95%CI [0.080;0.896] AS15 GS- Time (months) Louahed et al J Clin Oncol 26: 2008 (May 20 suppl; abstr 9045) 9
Slide 10: Predictive signature: benefit in NSCLC
Predictive signature: benefit in NSCLC Overall study population Gene signature positive 1.0 1.0 Disease Free Interval Distribution 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 HR = 0.75 (95% CI: 0.46-1.23) One-sided log rank p = 0.122 GS+: HR= 0.47 (95% CI: 0.20 - 1.13) 0.0 0.0 0 6 12 18 24 30 36 42 48 54 60 66
Slide 11: MAGE-A3 phase III: MAGRIT & DERMA
MAGE-A3 phase III: MAGRIT & DERMA MAGE-A3 positive MAGE-A3 positive Gene signature positive NSCLC MAGRIT MAGRIT Adjuvant setting – stage IB-II-IIIa (n=2270) Elevation of GS After or without chemo 33 countries; 400 sites as co-primary Melanoma DERMA DERMA Adjuvant setting – stage IIIb-c (n=1300) Elev
Slide 12: ASCI: diagnostic strategy
ASCI: diagnostic strategy Relapse Non-Relapse Paraffin slides GS- GS+ Protein MAGE-A3 mRNA • Pre-treatment tumour • MAGE-A3 expression • Presence of an sample above threshold expression pattern • Q-PCR based • Multi Q-PCR based 12
Slide 13: Collaboration with Abbott on MAGE-A3 diagnostic
Collaboration with Abbott on MAGE-A3 diagnostic Automated molecular diagnostic test Based on polymerase chain reaction (PCR) technology Using the Abbott m2000™ automated molecular instrument system NSCLC deal announced July 2009 Melanoma deal announced March 2010 13
Slide 14: Expanding the ASCI portfolio
Expanding the ASCI portfolio ASCI MAGE-A3 Combinations New antigens Chemo-radiotherapy Immunomodulation New tumour types WT1 Small molecules PRAME Bladder Hepatocarcinoma Gastric Oesophagus 14
Slide 15: Alzheimer's disease overview
Alzheimer’s disease overview Alzheimer’s disease • Most common cause of dementia - Incidence predicted to double by 2025 as the population ages • Two candidate vaccines in development - Phase I/II • Targets beta-amyloid - Pivotal role in plaque formation WHO: http://www.searo.who.int/LinkFiles/Healt
Slide 16: Nicotine addiction overview
Nicotine addiction overview Nicotine addiction • Nicotine conjugate vaccine (NicVAX) • Over - 1 billion smokers worldwide over 5 million tobacco-related deaths each year • Aid to smoking cessation and long-term abstinence • Produces antibodies that bind to nicotine in the bloodstream - prevents nico
Slide 17: GSK therapeutic vaccines: conclusions
GSK therapeutic vaccines: conclusions ASCI represent a novel class of compounds based on tumour antigens – Novel mechanism of action, tumour-specific, patient-selective Proof of concept for activity demonstrated in double-blind, randomised, placebo-controlled Phase II in NSCLC Second proof of concep
Slide 18: GlaxoSmithKline
GlaxoSmithKline