Scripps Florida Product Development Partnership for smoking cessation therapeutic

描述（由申请人提供）：烟草成瘾给社会带来的疾病负担和负面经济影响是惊人的。据预测，全世界约有6亿吸烟者将死于与吸烟有关的疾病，如慢性阻塞性肺疾病（COPD）、肺癌和心血管疾病。开发有效的戒烟辅助工具被认为是现代保健系统中最具成本效益的干预措施。虽然临床上有效，但目前的戒烟药物的效用非常有限。事实上，即使用目前最有效的药物Chantix和Zyban治疗，也有相当大的复发风险。由于据报道，使用这些药物会导致严重的精神健康事件，这两种药物现在也必须在标签上加上“黑盒子”警告。因此，药物治疗是帮助戒烟努力的有效策略，但迫切需要开发更安全、更有效的治疗方法。产品开发伙伴关系（pdp）是学术界、制药行业和慈善组织之间的合作成果，旨在发现、开发和提供新药。pdp弥合了研究与开发疾病之间的差距，而传统上工业对开发有效治疗方法的重视程度较低。佛罗里达斯克里普斯作为管理合作伙伴（MP）的戒烟治疗开发PDP机制的主要优势在于，它充分利用了我们在佛罗里达斯克里普斯研究所的核心使命，即开发帮助戒烟的药物，并将这种专业知识与PDP合作伙伴的科学和财务资源相结合。治疗方法将包括小分子（新的和重新利用的，rna，肽，抗体，和新的配方和递送机制）。在MITD的UH2阶段，我们将深入探讨为新一代戒烟产品建立成功的PDP的可行性。在UH3阶段，我们将执行下面描述的里程碑。在MITD PDP的UH2阶段实现的里程碑有：1)构建可搜索的生物信息学数据库，优先考虑治疗开发的靶点。然后，我们将使用数据库报告我们的发现，以及所有现有的关于烟草成瘾药物发现的科学和战略信息，作为对尼古丁成瘾发现过程的最全面审查；2)我们将与NIDA项目工作人员一起，在一个重要的科学会议（SRNT或CPDD）和FDA上组织一个研讨会，讨论当前的临床终点，以及开发生物标志物的潜力和效用。我们还将在佛罗里达TSRI-Scripps举办为期两天的峰会，所有UH2阶段的获奖者、NIDA项目官员、领先的学术科学家、可能加入PDP的现有和潜在行业合作伙伴、负责打击烟草成瘾和吸烟相关疾病的慈善基金会的代表，以及佛罗里达州卫生部的官员都将参加峰会。在本次峰会结束时，我们将确定最佳伙伴关系，以成功推动麻省理工学院PDP的使命。在MITD PDP的UH3阶段实现的里程碑是：1)我们将根据UH2阶段的发现填补一个强大的临床前/临床发现管道；2)到UH3的第3年，我们将有1个化合物进入II期临床试验；3)到UH3的第五年，我们将有1个化合物进入III期临床试验，另有1-2个化合物进入II期临床试验。

DESCRIPTION (provided by applicant): The burden of disease and negative economic impact of tobacco addiction on society is staggering. It is predicted that ~0.6 billion current smokers worldwide will die from smoking-related illnesses, such as chronic obstructive pulmonary disorder (COPD), lung cancer, and cardiovascular disease. The development of efficacious smoking cessation aids is considered the most cost-effective intervention possible within a modern health-care system. Although clinically efficacious, current smoking cessation agents have very limited utility. Indeed, there is considerable risk of relapse even when treated with the most efficacious medications currently available, Chantix and Zyban, which must also now carry "black box" warnings on their labeling because of reported serious mental-health events associated with their use. Pharmacotherapy is therefore an effective strategy to aid smoking cessation efforts, but there is a pressing need to develop safer and more effective therapeutics. Product Development Partnerships (PDPs) are a collaborative effort between academia, the pharmaceutical industry and charitable organizations that seek to discover, develop and deliver new medicines. PDPs bridge the gap between research and development for diseases for which there has traditionally been low priority in industry to develop effective therapeutics. The major advantage of the PDP mechanism for therapeutic development for smoking cessation with Scripps Florida as the Managing Partner (MP) is that it takes full advantage of our core mission at TSRI-Scripps Florida to develop medications to aid smoking cessation and combines this expertise with the scientific and financial resources of PDP partners. Therapeutics will include small molecules (novel and re-purposed, RNAs, peptides, antibodies, and novel formulations and delivery mechanisms). During the UH2 phase of the MITD, we will thoroughly explore the feasibility of establishing a successful PDP for the generation of new smoking cessation products. During the UH3 phase we will execute on the Milestones described below. The Milestones achieved during the UH2 phase of the MITD PDP are; 1) Construct a searchable bioinformatic database to prioritize targets for therapeutic development. We will then report our findings using the database, along with all available scientific and strategic information on drug discovery in tobacco addiction, as a most comprehensive review of the nicotine addiction discovery process; and 2) We will organize a symposium, in conjunction with NIDA program staff, at a major scientific meeting (SRNT or CPDD) and FDA to discuss current clinical endpoints, and the potential and utility for developing biomarkers. We will also host a 2-day summit at TSRI-Scripps Florida to which all awardees of UH2 phase grants, NIDA program officials, leading academic scientists, established and perspective industry partners who may join the PDP, representatives from charitable foundations charged with combating tobacco addiction and smoking- associated disorders, and officials from the State of Florida Department of Health. At the end of this summit, we will identify the optimal partnerships to successfully drive the mission of the MITD PDP. The milestones achieved during the UH3 phase of the MITD PDP are: 1) We will fill a robust preclinical/clinical discovery pipeline based on findings during the UH2 phase; 2) By year 3 of the UH3, we will have 1 compound entering Phase II clinical trials; and 3) By year 5 of the UH3, we will have 1 compound entering Phase III clinical trials, and another 1-2 compounds entering Phase II clinical trials. PUBLIC HEALTH RELEVANCE: The burden of disease and negative economic impact of tobacco addiction on society is staggering. It is predicted that ~0.6 billion current smokers worldwide will die from smoking-related illnesses, such as chronic obstructive pulmonary disorder (COPD), lung cancer, and cardiovascular disease. Indeed, if current trends in tobacco use persist, by 2020 smoking will become the largest single health problem worldwide, causing ~8.4 million deaths annually. The World Bank estimates that in high-income countries, smoking-related healthcare accounts for between 6-15% of all healthcare costs, ~$160 billion annually. Smokers who quit before the onset of tobacco-related illness can largely avoid the increased mortality risk. Nevertheless, ~80% of smokers currently attempting to quit will relapse within the first month of abstinence. The development of efficacious smoking cessation aids is considered the most cost-effective intervention possible within a modern health-care system. Product Development Partnerships (PDPs) are a collaborative effort between academia, the pharmaceutical industry and charitable organizations that seek to discover, develop and deliver new medicines. PDPs bridge the gap between research and development for diseases for which there has traditionally been low priority in industry to develop effective therapeutics (small market size etc).