Scripps Florida Product Development Partnership for smoking cessation therapeutic

描述（由申请人提供）：烟草成瘾对社会的疾病负担和负面经济影响是惊人的。据预测，目前全球约有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卫生保健系统中最具成本效益的干预措施。尽管临床上有效，但目前的戒烟剂具有非常有限的效用。事实上，即使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，由于报告了与使用相关的严重心理健康事件，这些药物现在也必须在标签上带有“黑框”警告。因此，药物治疗是帮助戒烟的有效策略，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，制药业和慈善组织之间的合作努力，旨在发现，开发和提供新药。PDP弥合了研究和开发之间的差距差距，因为传统上工业界对开发有效治疗方法的重视程度较低。以斯克里普斯佛罗里达为管理合伙人（MP）的PDP戒烟治疗开发机制的主要优势在于，它充分利用了我们在TSRI-Scripps佛罗里达的核心使命，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。治疗药物将包括小分子（新的和重新利用的RNA、肽、抗体以及新的制剂和递送机制）。在MITD的UH 2阶段，我们将彻底探索建立一个成功的PDP来生产新的戒烟产品的可行性。在UH 3阶段，我们将执行以下所述的里程碑。在MITD PDP的UH 2阶段期间实现的里程碑是：1）构建可搜索的生物信息学数据库，以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，沿着所有关于烟草成瘾药物发现的可用科学和战略信息，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，在一次重要的科学会议上组织一次研讨会（SRNT或CPDD）和FDA讨论当前的临床终点，以及开发生物标志物的潜力和实用性。我们还将在佛罗里达州的TSRI-Scripps举办为期2天的峰会，届时UH 2阶段赠款的所有获奖者、NIDA项目官员、领先的学术科学家、可能加入PDP的已建立和有前景的行业合作伙伴、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将出席会议。在本次峰会结束时，我们将确定最佳合作伙伴关系，以成功推动MITD PDP的使命。在MITD PDP的UH 3阶段实现的里程碑是：1）我们将根据UH 2阶段的发现填补一个强大的临床前/临床发现管道; 2）到UH 3的第3年，我们将有1种化合物进入II期临床试验; 3）到UH 3的第5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。 公共卫生相关性：烟草成瘾对社会的疾病负担和负面经济影响是惊人的。据预测，目前全球约有6亿吸烟者将死于与吸烟有关的疾病，如慢性阻塞性肺病（COPD）、肺癌和心血管疾病。事实上，如果目前的烟草使用趋势持续下去，到2020年，吸烟将成为全球最大的单一健康问题，每年造成约840万人死亡。世界银行估计，在高收入国家，与吸烟有关的医疗保健占所有医疗保健费用的6-15%，每年约1600亿美元。在与烟草有关的疾病发作之前戒烟的吸烟者可以在很大程度上避免增加的死亡风险。然而，目前试图戒烟的吸烟者中约有80%会在戒烟的第一个月内复发。开发有效的戒烟辅助工具被认为是现代卫生保健系统中最具成本效益的干预措施。产品开发伙伴关系（PDP）是学术界，制药业和慈善组织之间的合作努力，旨在发现，开发和提供新药。PDP弥合了研究与开发之间的差距，因为传统上工业界对开发有效疗法的优先级较低（市场规模小等）。

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).