CureSC Manufacturing Resource Platform

CureSC 制造资源平台

• 批准号: 10908840
• 负责人: Angelo A. Cardoso
• 金额: $ 178.56万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-27 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10908840
• 关键词: Address; Agreement; Annual Reports; Award; Biotechnology; CD34 gene; Cells; Cities; Clinical Trials; Communities; Doctor of Philosophy; Ensure; Evaluation; Funding; Goals; Gold; Human Resources; Infrastructure; Leadership; Lentivirus; Manufacturer; Measures; Modification; National Heart, Lung, and Blood Institute; Needs Assessment; Participant; Persons; Process; Production; Reagent; Research Personnel; Resources; Role; Science; Sickle Cell; Site; Site Visit; Structure; Surveys; Time; Travel; Treatment Efficacy; United States Food and Drug Administration; Work; assay development; cell community; cost; expectation; experience; gene therapy; interest; manufacture; meetings; member; programs; prospective; symposium; vector

An Other Transaction Agreement award would establish City of Hope and its principle investigator, Dr. Joseph Gold, in a leadership role to work with NHLBI to establish this resource over the next 3 years. • An initial activity for City of Hope would be the conduct of a needs assessment to ensure an understanding of the sickle cell community needs as it relates to cell and vector product manufacturing, along with associated reagents, for curative genetic therapies. This assessment would include an evaluation of the landscape of manufacturers and their current capacity to manufacture the identified products at the current study stages ongoing within the community. Such assessments would be conducted with the assistance of the current Cure SCI infrastructure; prospective PIs would be surveyed to understand their projected needs. A team of City of Hope experts with backgrounds in the treatment of SCD, CD34+cell modification, and GMP manufacturing (Joseph Rosenthal, MD; John Zaia, MD; Angelo Cardoso, MD, PhD; Joseph Gold, PhD; see attached biosketches) will assess the needs and determine how best to identify facilities with the expertise to help. • Following the assessment, in the first year City of Hope would create a strategy and plan for a consortium approach to the manufacturing resource platform for the CureSC initiative that covers vector and cell production for SCD, even if City of Hope is not a primary manufacturing site. We will also address the need for assay development to measure therapeutic efficacy and off‐target editing. This plan will address short‐term and long‐term goals and can evolve given the desire to build capacity over time. • NHLBI, working with through the leadership at City of Hope, would establish a consortium or network of manufacturers during the first year. This approach would address current demands by tapping into any excess capacity that may exist among this handful of places while manufacturers begin to build the capacity that will handle multiple investigators at once and reach the scale that will be needed to move CureSC science through to clinical trials. Yearly funding would be available to each consortium member to cover administrative and travel costs. We suggest that the consortium be comprised of 5 members (including CBG), selected from a number of sites that will have expressed interest in the consortium as a result of the survey performed by the outside entity. Members would then be selected based on their experience and capacity to take on SCD projects; this selection process would include site visits by Dr. Gold and, if needed, additional COH personnel. o NHLBI and COH will work together to ensure that the consortium is integrated into the overall infrastructure of the Cure Sickle Cell Initiative structure. It is expected that consortium members will work collaboratively with other Initiative members as well as outside entities, including academic, biotech, and other Federal partners (e.g. the US Food and Drug Administration). o Members of the consortium will be required to produce semiannual reports summarizing their activities that are relevant to the Cure SCI program. o In addition to regular conference calls among the consortium members, COH and NHLBI staff, we will establish a yearly in person meeting among the participants to review overall progress and to identify challenges and opportunities for the SCD community. o The NHLBI would allocate funds for projects estimated at $500,000 (the cost of a typical lentivirus production at CBG) at each of the 5 consortium members during year 2. In order to keep the consortium intact, year 3 funds would be allocated for consortium member administrative costs, with the expectation that NHLBI would allocate additional funding for new manufacturing projects, depending on the demand. Once established, the consortium can be kept intact and functional for additional years based on NHLBI’s funding. • It is anticipated that to provide the leadership and management necessary for this project, that the Other Transaction Agreement award would support City of Hope to bring on a project manager who would work closely with Dr. Gold to execute this project. • As part of an Other Transaction Agreement award, obligated funds will only be available for draw down by milestones that are collaboratively established with City of Hope and align to a larger work plan. These milestones can change over time through mutual agreement between NHLBI and City of Hope.

另一项交易协议将确立希望之城及其原则 调查员Joseph Gold博士担任领导职务，与NHLBI合作，在 接下来的三年。 ·希望之城的一项初步活动是进行需求评估，以确保 了解镰状细胞群体的需求，因为它与细胞和载体产品有关 制造，以及相关的试剂，用于根治性基因疗法。这项评估 将包括对制造商的情况及其目前的能力进行评估 在社区内正在进行的当前研究阶段生产已确定的产品。 这种评估将在现有的治疗SCI基础设施的协助下进行； 未来的私人投资机构将接受调查，以了解他们预计的需求。希望之城的团队 有SCD治疗、CD34+细胞修饰和GMP制造方面背景的专家 (约瑟夫·罗森塔尔医学博士；约翰·扎亚医学博士；安吉洛·卡多佐医学博士；约瑟夫·戈尔德博士；见附件 Biosketches)将评估需求并确定如何最好地确定具有以下专业知识的设施 帮助。 ·在评估之后，希望之城将在第一年制定战略和计划，以 针对CureSC计划的制造资源平台的联盟方法，包括 用于SCD的载体和细胞生产，即使希望之城不是主要制造地点。我们会 还解决了测试开发以测量治疗效果和非靶标编辑的需要。 这一计划将针对短期和长期目标，并可以根据建立 随时间推移的容量。 ·NHLBI与希望之城的领导层合作，将建立一个财团或 第一年的制造商网络。这种方法将通过以下方式解决当前需求 利用这几个地方可能存在的任何过剩产能，而制造商 开始建设一次处理多个调查人员的能力，并达到 将需要将CureSC科学转移到临床试验。每年都有资金可用 向每个财团成员支付行政和差旅费用。我们建议 财团由5名成员(包括CBG)组成，从多个地点中挑选将 由于外部实体进行的调查，已表示对该财团感兴趣。 然后，将根据他们承担SCD项目的经验和能力来挑选成员； 这一遴选过程将包括Gold博士的现场访问，如果需要，还将包括额外的COH人员。 O NHLBI和COH将共同努力，确保该财团整合到 治疗镰刀细胞倡议结构的整体基础设施。预计 财团成员将与其他倡议成员以及 外部实体，包括学术、生物技术和其他联邦合作伙伴(例如美国食品和药物管理局 和药品监督管理局)。 O财团成员将被要求提交半年度报告，总结 他们的活动与治愈脊髓损伤计划有关。 O除了财团成员之间的定期电话会议外，COH和NHLBI 工作人员，我们将在参与者之间建立年度面对面会议，以全面审查 在这方面，我们将继续取得进展，并找出SCD社区面临的挑战和机遇。 O NHLBI将为估计为500,000美元的项目分配资金(典型的 CBG的慢病毒生产)在第二年在5个联盟成员中的每一个成员。按顺序 为了保持财团的完整，第三年的资金将分配给财团成员。 行政成本，预计NHLBI将为以下项目分配额外资金 新的制造业项目，视需求而定。一旦成立，该财团 根据NHLBI的资助，可以保持完好无损并继续运行数年。 ·预计，为了提供该项目所需的领导和管理， 其他交易协议奖将支持希望之城聘请一名项目经理 将与戈尔德博士密切合作来执行这个项目。 ·作为其他交易协议奖励的一部分，义务资金仅可供提取 与希望之城合作建立的里程碑，并与更大的工作保持一致 计划。这些里程碑可以通过NHLBI和City of City之间的相互协议随着时间的推移而改变 希望。