CureSC Manufacturing Resource Platform

其他交易协议裁决将确立City of Hope及其原则 调查员约瑟夫·戈尔德博士担任领导职务，与NHLBI合作，在 未来三年。 ·“希望之城”的初步活动是进行需求评估，以确保 了解镰状细胞群体与细胞和载体产品相关的需求 沿着相关试剂，用于治疗性基因疗法。这一评估 将包括对制造商的前景及其当前能力的评估， 在社区内正在进行的当前研究阶段生产确定的产品。 这些评估将在现有的Cure SCI基础设施的协助下进行; 当局会向准私家侦探进行调查，以了解他们的预计需要。City of Hope希望之城 具有SCD治疗、CD 34+细胞修饰和GMP生产背景的专家 （Joseph Rosenthal，医学博士; John Zaia，医学博士; Angelo Cardoso，医学博士; Joseph Gold，博士;见附件 将评估需求，并确定如何最好地确定具有专门知识的设施， 帮助. ·评估后，希望之城将在第一年制定一项战略和计划， CureSC计划的制造资源平台的联盟方法，包括 即使City of Hope不是SCD的主要生产基地，也可以生产SCD的载体和细胞。我们将 还解决了测定法开发的需求，以测量治疗效果和脱靶编辑。 该计划将解决短期和长期目标，并可以根据建立 时间的能力。 ·NHLBI将通过City of Hope的领导层建立一个财团， 第一年的制造商网络。这一方法将通过以下方式满足当前的需求： 利用这少数几个地方可能存在的任何过剩产能， 开始建设同时处理多名调查员的能力，并达到 将需要将CureSC科学转移到临床试验。每年将提供资金 支付行政和差旅费用。我们建议 联合体由5名成员（包括CBG）组成，从多个地点中选出， 由于外部实体进行的调查，已表示对该联营集团感兴趣。 然后，将根据成员的经验和能力来挑选他们承担SCD项目; 该选择过程将包括Gold博士的现场访问，如果需要，还包括额外的COH人员。 o NHLBI和COH将共同努力，确保该联合体融入 治愈镰状细胞病倡议组织的整体基础设施。预计在 联盟成员将与其他倡议成员合作， 外部实体，包括学术、生物技术和其他联邦合作伙伴（如美国食品和药物管理局） 和药物管理局）。 联合体成员将被要求提交半年度报告， 他们的活动与治愈SCI计划有关。 o除了联合体成员之间的定期电话会议外，COH和NHLBI 工作人员，我们将建立一个年度会议的参与者之间的人，以审查整体 进展并确定SCD社区的挑战和机遇。 o NHLBI将为估计为500，000美元的项目分配资金（一个典型项目的费用）。 在CBG的慢病毒生产）在第2年期间在5个聚生体成员中的每一个中。为了 为了保持联合体的完整性，第三年的资金将分配给联合体成员， 行政费用，预计NHLBI将分配额外资金， 新的制造业项目，这取决于需求。一旦成立，财团 根据NHLBI的资金，可以保持完整和功能性。 ·预计为提供本项目所需的领导和管理， 其他交易协议奖将支持City of Hope聘请一位项目经理， 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，承付资金仅可用于提取 与City of Hope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 希望

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.