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02643 DESIGN AND PRECLINICAL DEVELOPMENT OF DENDRIMER BASED TOPICAL MICROBICIDES FOR HIV & STI PREVENTION McCarthy, Tom Dendrimers are a relatively new class of macromolecule characterized by highly branched, 3D architectures that are assembled in a precise, step-wise manner. This controlled synthesis allows the assembly of highly defined structures that radiate out in generations from a central initiator core. The result of this iterative growth process is a SINGLE macromolecular entity that contrasts with the mixture of molecules in traditional polymers or naturally occurring carbohydrates. In developing dendrimers as pharmaceuticals, we have had a focus on the prevention of HIV and STIs and the development of microbicide candidates. One approach investigated was the presentation of anionic groups on a variety of dendrimer scaffolds. Early examples of our polyanion coated dendrimers had activity against HIV and HSV which triggered a lead candidate optimization process and dendrimer SPL7013 was identified as a development candidate. Following a range of preclinical studies, we submitted an Investigational New Drug application (IND) for SPL7013 gel (VivaGel) to the United States FDA. SPL7013 represented the first time a dendrimer based product has been submitted to the FDA. Phase I safety studies are currently in progress. This presentation will describe the dendrimer based microbicide discovery phase, the lead candidate optimization process and selected data from the preclinical development of SPL7013. Dr Tom McCarthy |
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