Dimension is advancing therapies based on a next-generation adeno-associated virus (AAV) platform that has demonstrated early validation and compelling preclinical in vivo proof of concept across multiple disease states in leading academic research centers. Dimension’s current efforts focus on AAV8 and other forms of AAV that selectively target liver cells, and have been optimized to deliver missing intact genes in diseases associated with the liver. Initial indications of positive net benefit of this approach in patients, demonstration of robust gene expression in multiple preclinical in vivo models and commercially viable novel CMC approaches, provide a strong foundation for Dimension’s proprietary programs.
Engineered AAV Vectors
Dimension’s AAV vector technology consists of two components: the AAV capsid and AAV genome, which includes the human gene we are replacing. The capsid surface structure directs the AAV vector for entry into cells and can be engineered to enhance liver tropism. Within the vector, the non-integrating episomal AAV genome can be engineered to enhance cell-specific expression. Once inside the patient’s cells, the coding region of the AAV genome directs synthesis of the human therapeutic protein that is missing or deficient in patients.
Liver Targeting for Diverse Applications
There are nearly 1,000 liver-associated disorders, a broad number of potential indications from which Dimension can select specific diseases to target for application of its gene therapy platform. Dimension’s liver-targeted AAV platform allows the Company to strategically build the best product portfolio by actively pursuing programs that meet key criteria for advancement, including: 1) transduction and activity levels highly likely to result in clinically relevant efficacy; 2) well-understood disease biology and pathway, and 3) significant therapeutic needs. Six programs – in hemophilia A, OTC deficiency, GSDIa, citrullinemia type 1, PKU, and Wilson disease – are advancing either in or towards the clinic.