Procession to IND of a capsid mutated AAV8 codon optimized NAGLU vector for treatment of Sanfilippo Syndrome type B (Supplement)

About This Grant

Project Summary This supplement will enable the continued progress of the parent project to develop an AAV gene therapy product for the treatment of mucopolysaccharidosis type IIIB, a disease for which there is no current treatment. Specifically, this supplement performs the process and analytical development to optimize production methods and release criteria for tcm8AAV-coNAGLU as a drug substance prior to cGMP manufacture of the drug product. We will transition production to a suspension platform in order to scale up production volume consistent with the needs of a commercial product. This portion of the aims of the parent project were originally to be performed by the NIH BPN biologics contract development and manufacturing organization (CDMO) during the first and second year of the project, however, changes at NIH have prevented contracting with a CDMO to begin this process. We have the capacity to perform non-GMP virus manufacturing runs to optimize production methods and release criteria; develop master and working cell banks; develop reagent lists and protocols for production; and establish process and analytical methods development supporting characterization of tcm8AAV-coNAGLU (+/-CpG dep) drug substance. We did not have this capacity when the parent grant was submitted and did not budget for this or propose to do these functions at our institution but to have them done by NIH through the CDMO in accordance with the aims of the grant. In order to reach the milestones of the parent project, the process and analytical methods for scale up of tcm8AAVco-NAGLU production must be completed by year 3 in order to allow GMP grade manufacture during year 3 of sufficient quantity of drug substance for GLP toxicology starting in year 3. In cooperation and agreement with the lead development team participants from NIH and the NIH consultants, a statement of work for the planned CDMO contract was assembled. The University of Florida Powell Gene Therapy Center has created a Process and Analytical Development Group and hired scientists with industry experience in commercial AAV vector production to allow us to perform the project specific Process and Analytical Development at UF and at considerably less cost than is anticipated from CDMO bids. Specific aim 1: Perform non-GMP virus manufacturing runs to optimize production methods and release criteria; develop master and working cell banks; Develop reagent lists and protocols for production. Specific Aim 2: Establish process and analytical methods development supporting characterization of tcmAAV8-coNAGLU/CpGdepcoNAGLU drug substance (DS) and drug product (DP).