醫(yī)學(xué)交流課件：Respiratory SpectrumPresent and Future of Respiratory Treatments in AZ

1、Respiratory Spectrum: Present and Future of Respiratory Treatments in AZ 1 2 Advancing respiratory medicine to improve patients lives across three dimensions Inhaled therapies Targeted therapies Disease management AZs vision is to become an industry leader in innovative inhaled and targeted therapie

2、s for Asthma and COPD 3 Respiratory: Expanding breadth every four week dosing or potentially every eight week dosing Engineered for greater affinity for the Fc receptor on effector cells through afucosylation. Afucosylation leads to efficient eosinophil and basophil depletion, through enhanced antib

3、ody dependent cell- mediated cytotoxicity (ADCC) Source: M. Castro et al., Lancet Respiratory Medicine, 2014 Tralokinumab is a full human IgG4 monoclonal antibody targeting IL-13 IL-13 blockade has been shown to reduce the downstream signals that may mediate the central pathological features of pers

4、istent asthma: Smooth muscle contraction and proliferation Th2-type inflammation IgE production Mucus hypersecretion Collagen synthesis and deposition Possible biomarkers for IL-13 are Periostin and DPP4 Proposed indication: Adults and adolescents with inadequately controlled asthma on medium-high-d

5、ose inhaled corticosteroid/long acting 2 agonist (ICS/LABA) 7 9 AZD9412 (IFN-1a) inhaled biologic, first on-demand treatment to prevent asthma exacerbations Viral infection in one of the most frequent causes of asthma and COPD exacerbations Interferon beta (IFN-) produced as natural response. Inhale

6、d AZD9412 may boost suppressed immune response Ph2 INEXAS started 10 AZD1419 (iTLR-9 agonist) towards disease modification in asthma An exaggerated immune Type 2 response is a common underlying factor in asthma, this is part of the hygiene theory with TH1 to TH2 cell imbalance AZD1419 attempts to co

7、rrect the imbalanced immune response Rebalancing the immune system, aim to achieve disease-free periods Phase IIb planned for 2016 MEDI3506 MEDI3506 (anti-IL-33), a NME approved as a Candidate (CD): potential multiple indications including COPD An upstream initiator that controls the response to air

8、way insult Mechanism of action : anti-IL-33 MEDI3506 targets the top of the inflammatory cascade and inhibit multiple mechanisms involved in airways disease Potential to target a broad patient population 11 LAMA/LABAICS/LABA/LAMA ICS/LABA/LAMA plus: PDE-4; IL-5, ABs Emerging Paradigm Patients with b

9、ronchoconstriction and inflammation* Some patients need added protection against exacerbations Patients with bronchoconstriction LAMAICS/LABA ICS/LABA/LAMA plus: ABs, OCS Open airways, improve lung function, symptoms and activity Open airways and decrease inflammation & exacerbations Open airways an

10、d decrease inflammation and exacerbations and provide additional risk reduction * Medical history (exacerbation, clinical suspicion of asthma) and/or EOS180 Historical Paradigm AZs portfolio strategy in COPD BenralizumabPT010 AZ Portfolio 12 Conclusions AZ has a rich pipeline, anchored in new and emerging concepts derived from rigorous scientific exploration AZ aims to shaping current and future views on respiratory therapy by investigating, making bold decisions and working collaboratively with physicians, academia, other sponsors and