Slide 1: Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Pipeline: Cardiovascular & Metabolic Disease (CVMD) Addressing the next frontier in cardiovascular medicine Elisabeth Björk, Vice President, Head CVMD GMD
Slide 2: Cardiovascular & Metabolic Disease (CVMD): Strategy
Cardiovascular & Metabolic Disease (CVMD): Strategy Reducing CV morbidity, mortality and organ damage by addressing multiple CV risk factors Cardiovascular disease Metabolic disease Chronic kidney disease Atheros- CHD/ clerosis/ Heart Disease Symptomatic dyslipi- Diabetes NASH ACS failure progressio
Slide 3: Diabetes: Strategy to transform patient care
Diabetes: Strategy to transform patient care Shift treatment paradigm to early combination therapy and accelerate achievement of treatment goals Develop a science-led life cycle management strategy Expand into new areas of unmet need, including expansion into Type 1 diabetes with Forxiga 3 – Pipelin
Slide 4: Diabetes: R&D commitment
Diabetes: R&D commitment 2014 2015 2016 2017 2018 2019 DECLARE cardiovascular outcomes Type 1 diabetes Asia add-on to insulin Japan add-on to insulin saxa+dapa+met vs dapa+met saxa+dapa+met vs saxa+met saxa/dapa saxa/dapa vs sitagliptin saxa/dapa vs SU China add-on to insulin China initial combinati
Slide 5: Diabetes: Helping patients along disease progression
Diabetes: Helping patients along disease progression Sequential treatment 7.5 -Illustrative- HbA1c 7.0 6.5 6.0 Time 5 – Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Slide 6: Diabetes: New guidelines more aggressive with earlier combinations
Diabetes: New guidelines more aggressive with earlier combinations Note: AACE guidelines were published March 2013, SGLT-2 recommendation was based on Ph3 data. 6 – Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Slide 7: Oral combinations: Saxa/dapa & saxa/dapa/metformin
Oral combinations: Saxa/dapa & saxa/dapa/metformin Portfolio well-positioned to enable Significant reduction in HbA1c with early combination treatment low rates of hypoglycaemia Adjusted mean change from baseline in HbA1c at 24 weeks • Saxa/dapa added to metformin in poorly controlled T2DM – HbA1c r
Slide 8: Forxiga / Xigduo: Insulin doses remained stable over 2 years
Add-on to Insulin, 90-006 Forxiga / Xigduo: Insulin doses remained stable over 2 years • Dapagliflozin showed sustained reductions in HbA1c in when used in combination with insulin • Patients on dapa +insulin lost weight -3kg vs insulin alone • Insulin doses remained stable over the study period For
Slide 9: Diabetes: Potential of early combinations to slow disease progression
Diabetes: Potential of early combinations to slow disease progression Illustrative 9 – Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Slide 10: CVMD: Science-driven innovation into new areas of unmet need
CVMD: Science-driven innovation into new areas of unmet need NASH / Fatty Renal liver disease protection Type 1 Weight diabetes Heart failure 10 – Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Slide 11: CVMD: Visualising diabetes impact via differentiated technology
CVMD: Visualising diabetes impact via differentiated technology Body composition Tissue-specific Functional data Beta cell mass and ectopic lipids insulin sensitivity Healthy control Source: Merovci et.al JCI 2014 T1D patient Source: Nauck et.al Diabetes Care 2011 Automated body FDG (fluor-dioxygluc
Slide 12: Roxadustat (CKD): Potential to be first oral erythropoietic anaemia treatment
Roxadustat (CKD): Potential to be first oral erythropoietic anaemia treatment Hb correction in pre-dialysis CKD patients • Oral HIF-prolyl hydroxylase 100 inhibitor 90 Hb increase >1g/dL at 4 weeks, % • Favourable efficacy and 80 safety profile in Phase II 70 • >7,000 patient Phase III 60 ALPINE pro
Slide 13: Roxadustat (CKD): Potential for reduced cardiovascular risk vs. rEPO
Roxadustat (CKD): Potential for reduced cardiovascular risk vs. rEPO • Higher doses of rEPO predict USRDS: Unadjusted 1-year mortality by mortality regardless of epoetin dose & hematocrit hematocrit • Mechanism for increased CV risk with rEPO is uncertain, but may involve -supra-physiologic EPO leve
Slide 14: Roxadustat (CKD): Stimulates erythropoiesis similar to normal hypoxia response
Roxadustat (CKD): Stimulates erythropoiesis similar to the body’s normal coordinated response to hypoxia Median plasma EPO concentration at two oral doses of roxadustat postdialysis compared with • rEPO infusion produces reported EPO levels following IV administration supra-physiological EPO of rhEP
Slide 15: Brilinta (ticagrelor tablets)
pi. > BRILINTA. ticagrelor tablets
Slide 16: Brilinta: PARTHENON potentially transforms atherosclerosis treatment
Brilinta: PARTHENON potentially transforms atherosclerosis treatment 2014 2015 2016 2017 2018 2019 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 Prior MI Data Submission US/EMEA ; Japan China Stroke/TIA EMEA US Japan China Submission Data Peripheral Arterial Disease Data Submission EMEA US Japan China Diabete
Slide 17: Brilinta: PLATO results displayed unique clinical profile
Brilinta: PLATO results displayed unique clinical profile 13 7 Cumulative incidents (%) 12 Clopidogrel 11.7 CV death Cumulative incidents (%) 11 6 10 9.8 Clopidogrel 5 5.1 9 8 Ticagrelor 4 4.0 7 6 Ticagrelor 3 5 4 2 HR=0.79; 95% CI=0.69–0.91; p=0.001 3 (HR, 0.84; 95% CI, 0.77–0.92; P<0.001) 2 1 1 0
Slide 18: Brilinta: APOLLO UK proved unmet need in PEGASUS-like patients
Brilinta: APOLLO UK proved unmet need in PEGASUS-like patients APOLLO UK analysis 20 PEGASUS-TIMI-54 17.9% (16.2-19.5) Cumulative 3 year incidence of –Like Population ~1 in 5 PEGASUS-like CV death, MI or stroke (%) 15 (n=4,290) patients, event-free for 17.2% (16.0-18.5) 1 year post-MI, will 1 Year E
Slide 19: Summary
Summary Strategy of reducing morbidity, mortality and organ damage Diabetes growth from combo treatment and science-led LCM Opportunity to change the lives of CKD patients Transform atherosclerosis through Brilinta PARTHENON trials 19 – Pipeline: Cardiovascular & Metabolic Disease (CVMD)
Slide 20: Q&A
Q&A James Ward-Lilley, moderator Bing Yao Elisabeth Björk Chuck Bramlage Maarten Kraan Fouzia Laghrissi Thode Tom Keith-Roach