澳门在线赌城娱乐R&D生产力
概述
Following a major review of our research 和 development strategy in 2010, we created a new 5R Framework to guide how we discover 和 develop new drug c和idates. 回顾澳门第一赌城在线娱乐过去5年的生产力和成功率，澳门第一赌城在线娱乐现在可以看到澳门第一赌城在线娱乐的生产力发生了转变——使澳门第一赌城在线娱乐能够为患者发现比以往更多的创新疗法.
的一份新报告中 药物发现, 弥尼潘加洛斯, 澳门第一赌城在线娱乐公司执行副总裁&D 和 fellow scientists explain how our 5R framework (right target, 正确的病人, 正确的组织, 正确的安全, right commercial potential) has helped guide successful, 有效的药物发现和开发. 在短短五年内, 从临床前研究到完成III期临床试验，澳门第一赌城在线娱乐的管道分子比例提高了5倍，从4%提高到19%. 这一进步使澳门在线赌城娱乐大大超过了2013-2015年小分子药物平均成功率6%(数据来自CMR International的2016年全球R&D服务量度计划).
At the heart of this transformation has been a significant evolution of our culture. We have established an open, collaborative 和 ‘truth seeking’ culture where science thrives. 在这种环境下, we are never afraid to ask the ‘killer questions’ or to rigorously test our hypotheses. 这使澳门第一赌城在线娱乐能够提高澳门第一赌城在线娱乐进入临床前研究和随后进入临床试验的候选药物的质量.
澳门第一赌城在线娱乐的成功反映了一种不断发展的方法，澳门第一赌城在线娱乐正在整合最先进的技术来确定新的靶点和最新的转化科学，以确认澳门第一赌城在线娱乐的新型治疗方式在安全的治疗剂量下的机制证明，这些治疗方式可以用于人体研究.
澳门第一赌城在线娱乐不断展望未来, giving our scientists time for curiosity 和 original thinking, 让他们能够追随科学, 进一步提高澳门第一赌城在线娱乐的R&D success rate 和 deliver transformative treatments for patients.
注重品质
Underpinning the success of our 5R framework are changes in the way we conduct our research, which have enabled us to improve the quality of the c和idate drugs we take forward in our pipeline. Within a research culture where our scientists are encouraged to ask the ‘killer questions’, 澳门第一赌城在线娱乐严格地检验澳门第一赌城在线娱乐的假设, build confidence in promising targets 和 dismiss unfavourable ones much earlier in the discovery process.
Selecting the right target remains the most important decision we make in the drug discovery process. We aim to identify molecular drivers of disease across our main therapy areas: oncology, 心血管, 肾脏和新陈代谢, 呼吸学和免疫学, 通过澳门第一赌城在线娱乐全公司的基因组计划, 2016年4月推出.
“A selective high-quality molecule will never become a medicine if it is modulating the wrong target. This is why target selection is the most important decision we make in research.” 弥尼潘加洛斯, 澳门第一赌城在线娱乐公司执行副总裁&D
Building on our growing knowledge of disease biology, 澳门第一赌城在线娱乐已经扩大了澳门第一赌城在线娱乐研究的药物靶点的类别，澳门第一赌城在线娱乐越来越多地致力于识别具有新作用机制的化合物. 扩大澳门第一赌城在线娱乐的目标阶级构成, 对基因组数据的重大投资, next generation sequencing 和 CRISPR gene editing are enabling us to identify, interrogate 和 validate targets in a way not previously possible. 这意味着从发现活性化合物到优化分子的成功率从23%提高到48%.
整合临床前吸收, 分布, 新陈代谢, 将ADME和安全性数据用于预测药物对患者的作用，从而提高候选药物的质量. 澳门第一赌城在线娱乐正在推进最佳实践, predictive 和 translational science needed to show target engagement 和 proof of mechanism at safe, therapeutic doses that can be taken into human studies. 结果是, we are delivering better quality c和idates that are less likely to fail due to safety or other issues at later development stages.
To enhance our ability to match the right medicine to the 正确的病人, we plan for biomarker-guided patient stratification at an early stage of our drug discovery projects. 通过建立可Search的, accessible human tissue biobanks for our scientists, 澳门第一赌城在线娱乐正在支持生物学从临床到实验室的转化，这有助于改进筛选分析和新的生物标志物. 因此, 2012-2016年，从Lead优化开始，澳门第一赌城在线娱乐的投资组合中约有80%具有患者选择策略，而2005-2010年这一比例不到50%. Today, this figure is greater than 90% across our therapy areas.
Our focus on defining the ‘正确的病人’ has enabled us to launch nine companion diagnostics tests in 2012–2016, 相比之下，2005-2010年只有一个. We have already introduced biomarker-based diagnostic tests for EGFR, 表皮生长因子受体T790M, BRCA 和 PD-L1 to identify patients most likely to benefit from our targeted treatments for non-small cell lung cancer, 卵巢癌和膀胱癌. We also pioneered new tests using circulating tumour DNA as the biological sample type to broaden patient access.
By adapting 和 redesigning our preclinical 和 early phase clinical trials, we are setting rigorous st和ards so we rapidly 和 efficiently select only the best c和idates for further development. Through the continued evolution 和 application of our 5R framework, we are converting our preclinical data into knowledge to be used to improve clinical study decision making, 从而缩小数据到知识的差距. AstraZeneca is already being recognised as leading the way in the application of artificial intelligence (AI) in early clinical trials through the iDecide research programme – an innovative five year collaboration between AstraZeneca, the University of Manchester Institute of Cancer Sciences, the Centre for Cancer Biomarker Sciences 和 the Christie NHS Foundation Trust (digitalECMT). 结果是, 澳门第一赌城在线娱乐可以做严格的, quantitative decisions about the drug c和idates we progress to the later stages of development.
“The Manchester collaboration is a tremendous opportunity for industry 和 academia to work h和 in h和 with patients. 它将澳门在线赌城娱乐团队聚集在一起, 欧洲最大的癌症医院的临床医生, University of Manchester scientists 和 Cancer Research UK. Together we can innovate in the conduct of clinical trials 和 the application of AI.” says Professor Andrew Hughes, Clinical Lead for Manchester Experimental Cancer Medicine.
发现新的生物学
澳门第一赌城在线娱乐遵循科学的战略核心是决心推进澳门第一赌城在线娱乐对疾病生物学的基本理解，以发现澳门第一赌城在线娱乐想要治疗的疾病的新驱动因素, 防止, 修改甚至治愈. 澳门第一赌城在线娱乐相信澳门第一赌城在线娱乐的方法是独一无二的. 澳门第一赌城在线娱乐不只是与世界专家合作, 澳门第一赌城在线娱乐与优秀的学术中心建立了联合实验室，澳门第一赌城在线娱乐的科学家与学术科学家并肩工作. Our teams are committed to discovering how changes in cell biology lead to diseases such as cancer, lung 和 immune disorders 和 heart 和 metabolic diseases. 澳门第一赌城在线娱乐还致力于分享澳门第一赌城在线娱乐的研究资产，如筛选集合和临床化合物，以实现澳门第一赌城在线娱乐的开放式创新倡议下的学术研究.
作为这些合作的结果, we have published novel biological findings in several high impact journals together with our partners. In the past 18 months alone, this has included papers in 自然医学, 科学转化医学, 循环 和 科学的进步. 在肿瘤学, through a highly successful collaboration with the Medical Research Council’s Laboratory of Molecular Biology, we used state-of-the-art cryo-electron microscopy (cryoEM), 来描述, 第一次, the structure 和 activation mechanism of human ataxia-telangiectasia mutated (ATM) protein. 这种蛋白质是一个关键的触发因素 DNA损伤反应(DDR) 和 this collaborative work has resulted in insights that will help us uncover novel binding sites for future drug targeting.
通过澳门第一赌城在线娱乐的呼吸和免疫学研究, 澳门第一赌城在线娱乐已经确定了树突细胞的亚群, 叫做cDC2细胞, that are essential for priming the immune response against invaders. 确定cDC2细胞如何以及在何处适应复杂的免疫过程，使澳门第一赌城在线娱乐能够检查由不适当的抗体反应(如哮喘)驱动的疾病中的新靶点, chronic obstructive pulmonary disease 和 autoimmunity.
在心血管, 肾脏和代谢性疾病, 澳门第一赌城在线娱乐广泛的心脏再生研究计划正在确定可能在心力衰竭患者修复受损心肌中发挥作用的新靶点和途径. In recent studies with Professor Bin Zhou at the University of Chinese Academy of Sciences in Shanghai, 澳门第一赌城在线娱乐强调了 旁分泌因素的重要性 在心脏再生中.
With our scientists at the AstraZeneca Integrated Cardio Metabolic Centre (AZ-ICMC) at the Karolinska Institute, we have contributed two seminal pieces of research to the underst和ing of diabetes. 通过确定胰岛素样生长因子1 (IGF1)在驱动心脏有害心外膜脂肪组织形成中的新作用，澳门第一赌城在线娱乐为解决心脏病和肥胖日益增加的负担开辟了新的机会. 除了, by elucidating the functionality of sub-sets of islet cells in the pancreas, we have improved underst和ing of their importance in diabetes.
在神经科学, 澳门第一赌城在线娱乐在塔夫茨大学澳门在线赌城娱乐-塔夫茨神经科学实验室的科学家们正在为大脑神经兴奋的控制机制带来新的见解, including increasingly detailed knowledge of the essential role of neuronal potassium-chloride transporter protein (KCC2). We are collaborating with researchers at the University of 剑桥 to study the cellular processes for degrading unwanted proteins, with the aim of activating these mechanisms to degrade misfolded proteins such as huntingtin in Huntington’s disease.
“We are interested in partners who are curiosity based, who believe that underst和ing the science will shorten the route to clinic. 澳门第一赌城在线娱乐与澳门在线赌城娱乐的合作是天作之合，因为澳门在线赌城娱乐真正专注于科学和“蓝天”思维，这是由当前最先进的知识提供的.” 伊恩·麦金尼斯教授, 导演, 感染研究所, 免疫与炎症, 格拉斯哥大学
把科幻小说变成科学事实
在药物发现和开发的各个阶段, we are seeking solutions to the ‘what if’ questions of today. By investing in the latest cutting-edge technologies, we are accelerating progress towards our goal of delivering the targeted, 改变未来生活的药物.
当澳门第一赌城在线娱乐运用疾病生物学的知识, we are diversifying our chemical toolbox to develop new therapies against an array of drug target classes. We no longer focus on small molecules alone, with around 30% of our programmes now exploring new modalities 和 drug delivery devices as part of our effort to make every target druggable.
Our everyday use 和 development of CRISPR/Cas 9 provides fast, 精确的, efficient gene editing to help us discover new drug targets 和 create more relevant cell lines 和 animal models. Through world-leading partnerships 和 our in-house team of experts, we continually push the technology to improve screening 和 efficiency. 在最近的两份高影响力出版物中, 澳门第一赌城在线娱乐展示了如何使用条形码引导RNA来改进筛选和开发新型杂交DNA:RNA引导来提高结合效率.
Speeding up the automated testing of thous和s of potential new molecules is NiCoLA-B – the world’s most advanced drug discovery robot. NiCoLA-B利用声波将潜在药物的微小液滴从储存管中移动到分析板上的微型“孔”中，每次可以移动十亿分之一升.
Our investment in multimodal molecular imaging is enabling us to uncover new insights into our drug targets, 和 to see the impact of our drug c和idates on molecular 和 cellular pathways in ways that were previously impossible. 质谱法, we have created detailed images of the deposition of asthma drugs in multiple structures of the lung over time. 澳门第一赌城在线娱乐还绘制了靶向癌症治疗组合的药物和代谢物分布，以评估其对肿瘤微环境的影响.
To further improve our ability to predict the effects of our drug c和idates on humans, we are collaborating with world-leading experts in ‘organ-on-a-chip’ design, technology 和 biology to develop microphysiological systems (MPS).
澳门第一赌城在线娱乐的工作进展迅速 基因组计划 和 next-generation sequencing (NGS) are enabling us to identify novel targets 和 pathways within large patient populations. 事实上, 澳门第一赌城在线娱乐已经分析了200多个,000 of the 2 million genomes we plan to explore by 2026, 其中包括500,从澳门第一赌城在线娱乐自己的临床试验中. This is supported by on our recent partnership with UK Biobank 和 Regeneron to sequence the genomes of 500,000个英国生物银行样本, to accelerate the largest widely-available ‘big data’ human sequencing resource.
人工智能已经在帮助澳门第一赌城在线娱乐解决化学领域的最大挑战，基于人工智能的信息学也开始将“大数据”转化为有价值的知识. 新型人工智能技术的开发目前正应用于正在进行的临床试验，以改进安全性和耐受性信号的识别和预测. 观察家, is an AI-driven system that notifies clinicians 和 study teams involved in clinical trials of potential safety issues. 该系统可以对临床试验数据进行“推理”，以评估特定临床事件的风险，使团队能够尽早采取适当的行动.
“观察家 is a decision support system being developed to continuously monitor specific patient risk 和 alert the study team early. Our aim is that Watcher will ultimately identify those patients at potential risk before they materialize 和 ameliorate this same risk.” Dónal兰德斯博士说, Senior 导演 Physician OncTMU Early Clinical Development 导演 – iDecide Programme, 克鲁克曼彻斯特学院
在R&D we will never be complacent; we will continually look beyond the way we develop drug c和idates today 和 explore how we can best use emerging technologies to accelerate the design 和 testing of tomorrow’s medicines. 通过澳门第一赌城在线娱乐的新药物发现平台, we are moving towards multiple classes of medicines that target the biology of disease in totally new ways. By replacing today’s conventions with tomorrow’s innovations, 澳门第一赌城在线娱乐正在把科幻小说变成科学事实.
