VivaZome Therapeutics is a small privately-held, Melbourne based biotech company developing exosome-based therapeutics for debilitating and life-threatening disease. The underpinning premise for exosome therapeutics is that cell secreted exosomes can deliver a combination of biological cargo to target cells thereby regulating their function and changing the course of an underlying disease. VivaZome’s initial clinical indication is treatment of critical limb ischaemia. Development of a scalable manufacturing process for therapeutic exosomes is underpinned by a phase appropriate quality management system and consideration of the clinical and regulatory requirements for such a product. Our manufacturing process development is informed by a target product profile (TPP) which defines the nature and use of the final exosome product.
The VivaZome approach for manufacture of therapeutic exosomes is to based on separation and concentration of exosomes from spent cell culture media, which is the starting substrate for the downstream process. Using a range of assays, VivaZome has screened the cell culture supernatant from multiple human cell types to identify cells that secrete abundant exosomes with angiogenic potential. Exosome analysis includes quantitation, by qrt-PCR, of miRNA species known to promote angiogenesis and also small RNA sequencing to compare the miRNA signature of vesicles secreted from different cell types. These studies have shown that exosomes have distinct molecular signatures from their parental cells and from each other. The angiogenic potential of exosome fractions has been demonstrated in an endothelial tube forming assay.
We are currently evaluating automated, closed, perfusion-based bioreactor systems for large scale culture of our preferred cell type. We have demonstrated that cells can cultured for up to 10 days and secrete high numbers of vesicles. VivaZome is assessing a number of technologies including size exclusion chromatography, affinity chromatography, tangential flow filtration and new approaches for exosome concentration are being tested; the results of these studies will be highlighted.