Slide 1: Fostamatinib Analyst Briefing
Fostamatinib F t ti ib Analyst Briefing 15 November 2012 Item owner: Christopher Sampson
Slide 2: Cautionary Statement Regarding Forward-Looking Statements
Cautionary Statement Regarding F Forward-Looking d L ki Statements St t t •In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This presentation contains certain forward f
Slide 3: Today's Agenda and Presenters
Today’s Agenda Presenters 1. The opportunity in RA Liza O’Dowd, MD 2 What 2. Wh t is i Fostamatinib F t ti ib Gl b l Product Global P d t VP 3. Mechanism of action 4. Phase II data and safety Chris O’Brien Medical Science Director 5. Design of Phase III and the OSKIRA programme 6. Questions and Answ
Slide 4: Why rheumatoid arthritis? A prevalent disease with significant unmet need
Why rheumatoid arthritis? A prevalent disease with significant unmet need 1 people worldwide are affected by RA1 in 100 years old is the typical age when RA symptoms appear,2 35 – 50 with women 3x more likely to be affected than men3 9 RA patients treated with disease-modifying therapy Million (trad
Slide 5: Rheumatoid arthritis is painful and debilitating
Rheumatoid arthritis is painful and debilitating Early RA RA with moderate joint deformity severe RA • Chronic, Ch i systemic, t i autoimmune t i disease di • RA causes painful, swollen, and tender joints • Over time, inflammation in the joints can lead to joint damage including erosion of cartilage
Slide 6: Patients go through several lines of treatment
Patients go through several lines of treatment ~$14bn RA market expected to reach $18bn in 2022 First line therapy Second-line therapy Third-line Early Tx (generic oral DMARDs – (iv/sc biologics – therapy (NSAIDs) typically Methotrexate) typically anti-TNF) (other biologics) g ) 10-15% patients ((50
Slide 7: About fostamatinib
About fostamatinib • Fostamatinib was in-licensed from Rigel Pharmaceuticals, Inc. in February 2010 for an initial upfront payment of $100m AZ has full development and commercial rights (except respiratory indications). • Fostamatinib is a novel MOA, oral kinase inhibitor that has selectivity for SY
Slide 8: Mechanism of action
Mechanism of action • Fostamatinib is an oral kinase inhibitor that has selectivity for SYK • SYK has a broad role in RA autoimmunity, inflammation, and tissue damage
Slide 9: Fostamatinib Phase II data
Fostamatinib Phase II data
Slide 10: Ph IIa TASKi1 Study Design
Ph IIa TASKi1 Study Design 0 week 12 weeks 16 weeks Cohort 3: Fostamatinib 150 mg bid po + MTX, n = 47 FU Responders (ACR ≥50 at 12 weeks) Active A ti RA C h t2 Cohort 2: F Fostamatinib t ti ib 100 mg bid po + MTX MTX, n = 49 FU despite treatment Fostamatinib + MTX with MTX Cohort 1: Fostamatinib 50
Slide 11: Ph IIa TASKi1 ACR Response Rates
Ph IIa TASKi1 ACR Response Rates at Week 12 80 ** p < 0.01 *** p < 0.001 Placebo *** Fostamatinib 50 mg bid ders (%) 70 ** Fostamatinib 100 mg bid 60 *** Fostamatinib 150 mg bid portion off respond 50 ** 40 *** *** 30 20 Prop 10 0 ACR20 ACR50 ACR70 Primary Objective As pre-specified, all dropout pat
Slide 12: Ph II TASKi2 Study Design
Ph II TASKi2 Study Design Open-label extension study 0 6m (monthly safety and efficacy assessments) Fostamatinib 100 mg bid po + MTX, n = 152 Active RA RA, Fostamatinib 150 mg qd po + MTX, despite n = 152 treatment Fostamatinib + MTX with MTX Placebo bid po + MTX, n = 76 Placebo qd + MTX, n = 77 ACR
Slide 13: Ph II TASKi2 ACR Response Rates at Month 6
Ph II TASKi2 ACR Response Rates at Month 6 ** p < 0.01 *** p < 0.001 Placebo 80 Fostamatinib 150 mg qd Fostamatinib 100 mg bid ortion of rresponders (%) 70 *** 60 *** 50 *** 40 ** 30 *** 20 Propo 10 0 ACR 20 ACR 50 ACR 70 Primary Objective As pre-specified, all dropout patients were considered ACR n
Slide 14: Ph II TASKi2 ACR Response Rates at Week 12
Ph II TASKi2 ACR Response Rates at Week 1 ** p < 0.01 *** p <0.001 Placebo 40 Fostamatinib 150 mg qd *** Fostamatinib 100 mg bid ers (%) 35 30 ortion of rresponde 25 20 15 10 *** Propo 5 0 ACR 20 ACR 50 ACR 70 As pre-specified, all dropout patients were considered ACR non-responders at all time poin
Slide 15: Ph II TASKi2 Patient Reported Adverse Events
Ph II Taski2 Patient Reported Adverse Events Most Frequent Adverse Events (>5%) Fostamatinib Fostamatinib Placebo 150 mg qdd 100 mg bid Diarrhea 3.0% 11.8% 19.1% Upper Respiratory Infection 7.1% 7.2% 14.5% Urinary Tract Infections 4.6% 3.3% 5.9% Neutropenia 0.7% 6.6% 5.9% Headache 5.2% 6.6% 5.9% Abd
Slide 16: Ph II TASKi3 Study Design
Ph II TASKi3 Study Design Open-label p extension study 0 3 mo (monthly safety and efficacy assessments) Fostamatinib 100 mg bid po + MTX, Active RA RA, n = 146 despite treatment with a Fostamatinib + MTX biologic therapy Placebo bid po + MTX, n = 73 ACR20 (P i (Primary endpoint) d i t) Primary y Obj
Slide 17: Ph II TASKi3 ACR Response Rates
Ph II TASKi3 ACR Response Rates at Month 3 45 Placebo Fostamatinib 100 mg bid 40 ers (%) 35 ortion of rresponde 30 25 20 15 10 Propo 5 0 ACR 20 ACR 50 ACR 70 Primary Objective As pre-specified, all dropout patients were considered ACR non-responders at all time points after withdrawal Genovese MC, e
Slide 18: OSKIRA Clinical Programme
OSKIRA Clinical Programme
Slide 19: OSKIRA Ph III Studies Reporting in 1H 2013
OSKIRA Ph III Studies Reporting in 1H 2013 Planned Pl d US/EU 2013 Regulatory Submission MTX Combination, Combination N= 922, 922 12 months 2H 2013 Status: Enrollment completed DMARD Combination, N = 913, 12 months Status: Enrollment completed p MTX Combination in αTNF failures, N=322, 6 months Stat
Slide 20: Fostamatinib evidence base in RA
Fostamatinib evidence base in RA Evidence in second-line MTX-IR and Evidence in third- DMARD-IR populations provided by line TNF-IR OSKIRA-1 and OSKIRA-2 population provided by OSKIRA-3 First line therapy Second-line therapy Third-line Early Tx (generic oral DMARDs – (iv/sc biologics – therapy (NSAI
Slide 21: Q&A
Q&A
Slide 22: Backup Slides
BACKUP SLIDES
Slide 23: Fostamatinib and rheumatoid arthritis Key facts
Fostamatinib and rheumatoid arthritis Key facts 1 Fostamatinib is an oral kinase inhibitor that has selectivity for spleen tyrosine kinase (SYK) in development for rheumatoid arthritis. It is being studied as an alternative to injectable j therapies p for rheumatoid arthritis. 2 Rheumatoid arthritis
Slide 24: Phase III design: OSKIRA 1 and 2
Phase III design: OSKIRA 1 (MTX-IR) and 2 (DMARD IR) (DMARD-IR) Male and female patients aged 18 years or over, with active RA despite current treatment. Placebo controlled Active extension 0 period 24 weeks period 52 weeks Fostamatinib 100 mg bid + Continue MTX/DMARD Randomisation to one of three d
Slide 25: Phase III design: OSKIRA 3
Phase III design: OSKIRA 3 P ti t with Patients ith an iinadequate d t response tto a single i l TNF TNFα antagonist t i t 0 24 weeks Fostamatinib 100 mgg bid + MTX Randomisation to one of three dosing regimens Fostamatinib 100 mg bid for 4 weeks + MTX, followed by 150 mg qd + MTX (1:1:1) N = 322 Pl
Slide 26: Design of Phase II OSKIRA-4 study
Design of Phase II OSKIRA-4 study Months 0 1 2 3 4 5 6 Fostamatinib 100 mg bid po + placebo injection q2w Long-term extension study Fostamatinib 150 mg qd po (OSKIRA X) (OSKIRA-X) Induction* + placebo injection q2w Patients completing 52 weeks of treatment Patients with active RA Fostamatinib 100 mg