CureSC Manufacturing Resource Platform

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.

Grant Number: 3OT3HL152932-01S2
NIH Institute/Center: NIH
Principal Investigator: Angelo Cardoso