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.
